Lecture on biomarkers (principles, potentials, pitfalls) for 200 pharmaceutical professionals as part of the IMI Pharma Train course organised by the European Center for Pharmaceutical Medicine
2016-02-18 Innovation for Health 2016 conference, Rotterdam Alain van GoolAlain van Gool
Lecture on personalized healthcare in a great session at the Innovation for Health 2016 conference, discussing opportunities and challenges with 800 scientists, enterpreneurs and care professionals.
Great evening with the Rotary Oss where I got the opportunity to discuss current and future prospects in personalized healthcare with a good group of interested people.
2016 04-21 Association of Dutch Producers of Children and Diet Nutrition (VNF...Alain van Gool
Keynote lecture at the 55-year lustrum conference of the Association of Dutch Producers of Children and Diet Nutrition (VNFKD) to reflect on the use of (specialized) nutrition in personalized healthcare.
2016 08-22 Radboud Grand Round, Nijmegen, Alain van GoolAlain van Gool
Interactive lecture with a large group of healthcare professionals, scientists and patients to illustrate developments in personalized healthcare and the role of technology to support science, innovations and medical impact. (slides in English)
2016 11-01 Biomarker Agora, Copenhagen, Alain van GoolAlain van Gool
This document discusses the development and validation of clinical molecular biomarkers. It begins with an example of how the B-RAFV600E mutation in melanoma can be used for personalized medicine approaches. It then describes efforts to validate interleukin-8 (IL-8) as a biomarker for ERK pathway inhibition, which involved extensive biomarker profiling and validation studies but ultimately found the data to be irreproducible. The document emphasizes the need for improved biomarker validation practices and increased collaboration to address gaps between biomarker discovery and clinical application.
2016 09-12 Europe Biobanking Week, Vienna, Alain van GoolAlain van Gool
Opening keynote of the Europe Biobanking Week, outlining reasons why we should join forces in validation and development of biomarker in personalized medicinand health.
2016-02-18 Innovation for Health 2016 conference, Rotterdam Alain van GoolAlain van Gool
Lecture on personalized healthcare in a great session at the Innovation for Health 2016 conference, discussing opportunities and challenges with 800 scientists, enterpreneurs and care professionals.
Great evening with the Rotary Oss where I got the opportunity to discuss current and future prospects in personalized healthcare with a good group of interested people.
2016 04-21 Association of Dutch Producers of Children and Diet Nutrition (VNF...Alain van Gool
Keynote lecture at the 55-year lustrum conference of the Association of Dutch Producers of Children and Diet Nutrition (VNFKD) to reflect on the use of (specialized) nutrition in personalized healthcare.
2016 08-22 Radboud Grand Round, Nijmegen, Alain van GoolAlain van Gool
Interactive lecture with a large group of healthcare professionals, scientists and patients to illustrate developments in personalized healthcare and the role of technology to support science, innovations and medical impact. (slides in English)
2016 11-01 Biomarker Agora, Copenhagen, Alain van GoolAlain van Gool
This document discusses the development and validation of clinical molecular biomarkers. It begins with an example of how the B-RAFV600E mutation in melanoma can be used for personalized medicine approaches. It then describes efforts to validate interleukin-8 (IL-8) as a biomarker for ERK pathway inhibition, which involved extensive biomarker profiling and validation studies but ultimately found the data to be irreproducible. The document emphasizes the need for improved biomarker validation practices and increased collaboration to address gaps between biomarker discovery and clinical application.
2016 09-12 Europe Biobanking Week, Vienna, Alain van GoolAlain van Gool
Opening keynote of the Europe Biobanking Week, outlining reasons why we should join forces in validation and development of biomarker in personalized medicinand health.
2016 09-21 symposium Opening the BBMRI genomics infrastructure in The Netherl...Alain van Gool
Keynote lecture for the BBMRI genomics community at this BBMRI symposium, outlining my perspective on personalized medicine and health, and the various activities within The Netherlands to shape the healthRI.
2016 11-15 Lygature partnership meetup, Utrecht, Alain van GoolAlain van Gool
Contribution to the opening of the Joint Innovation Mile in the Beatrix building in Utrecht, home of the offices of Lygature, HealthRI, BBMRI-NL and others to follow.
2016 09-08 Copenhagen Bioscience Lecture, Alain van GoolAlain van Gool
On invitation of the Novo Nordisck Foundation, an interactive story on personalized healthcare, biomarkers and innovation in proteomics for a group of enthousiastic young scientists.
2021 03-25 11th World Clinical Biomarkers & Companion Diagnostics, Alain van ...Alain van Gool
Closing keynote of a 3-day conference on clinical biomarkers and companion diagnostics, organised by Hanson Wade, outlining the power of omics approaches in healthcare and translation of inovations to impact.
2020 08-28 SensUs Event 2020 keynote, Eindhoven, Alain van GoolAlain van Gool
Closing keynote for international students participating in the SensUs Event 2020, where they designed and created a novel sensor for drug level monitoring in epilepsy treatment. Lecture outlined innovations in biomarkers in personalized health(care).
2020 09-07 European Center Pharmaceutical Medicine course Biomarkers, Basel, ...Alain van Gool
Tutorial lecture on biomarkers for pharmaceutical industry R&D professionals, outlining status, potential and challenges of biomarkers in pharma, clinic and society.
2015 12-09 Opening Radboud Translational Medicine, Nijmegen, Alain van GoolAlain van Gool
Keynote opening lecture at the grand opening of our new cyclotron facility, embedded in Radboud Translational Medicine and part of our Radboudumc Technology Centers. See http://www.radboudtranslationalmedicine.nl/nl/ for details.
2019 06-19 Dutch association for clinical chemistry and laboratory medicine -...Alain van Gool
Sharing my views on how X-omics biomarker analyses through next gen sequencing and mass spectrometry will change the landscape of diagnostics and clinical chemistry in the near future.
2020 02-10 European Center Pharmaceutical Medicine course - biomarkers, Basel...Alain van Gool
This document discusses biomarkers and personalized healthcare. It begins with an overview of biomarkers in the pharmaceutical industry and how they are used from drug discovery through clinical trials. It then discusses biomarkers in academic research and healthcare, and how emerging digital biomarkers could enable personalized health monitoring. The presentation identifies some translational innovation gaps, and concludes with an outlook on how biomarkers and multi-omics approaches will continue to advance personalized diagnosis and therapies.
2015 07-03 Nanonext NL Alain van Gool, AmsterdamAlain van Gool
The document discusses implementing personalized healthcare through measuring biomarkers. It notes that while many biomarkers have been discovered, few are validated and applied in diagnostic tests. There is also a gap in translating biomarkers into point-of-care applications. The document advocates for open innovation networks to help validate biomarkers across multiple centers and standardize clinical applications. Ultimately, the focus of personalized healthcare should be on the patient by providing individualized follow-up based on their molecular and clinical measurements.
2018 03-01 International Conference on Perspectives in Precision Medicine, Co...Alain van Gool
This keynote lecture reviews the historical and ongoing investments in public-private partnerships related to precision medicine and the related technological infrastructures. It served as example to the Danish community how translational biomarkers in precision medicine can be organised, as basis for further collaboration between Denmark and Netherlands.
2021 06-14 EATRIS-Plus summer school, Alain van GoolAlain van Gool
Introductory lecture for the 100 participant summer school of the EATRIS-Plus project, outlining personalized medicine, biomarker and multi-omics strategies and use cases.
2018 11-26 KNAW-AcTI symposium Personalized Health, Amsterdam, Alain van GoolAlain van Gool
Lecture at a citizen discussion evening, reviewing the promises and (ethical) considerations of technology developments to support personalized health, organised by the Royal Academy of Sciences and the Netherlands Academy of Technology and Innovation.
2019 10-14 2nd Int Congress on Precision Medicine, Munich, Alain van GoolAlain van Gool
Opening lecture at the 2nd International Congress on Precision Medicine in Munich, outlining progress in omics-based biomarkers for rare diseases, biomarker innovation gaps and multi-partner initiatives to bridge those gaps to applications. Also reviewed the highlights of our recently published Handbook of Biomarkers and Precision Medicine.
2015 09-14 Precision Medicine 2015, London, Alain van GoolAlain van Gool
Outline of my view hoe personalized health(care) is more than just targeted medicines, also including personal motivation and actions towards disease prevention. It also outlines 4 key factors that should be in order for optimal personalized health(care): 1. start with patients first, 2. Accelerate translation research to application, 3. Copy best practice, 4. Spread the word.
From Bits to Bedside: Translating Big Data into Precision Medicine and Digita...Dexter Hadley
Lecture Objectives:
1) To use examples from my research to define and introduce the ideals of precision medicine and digital health. 2) To introduce how large scale population-wide analysis of data can be used to facilitate these two ideals. 3) To introduce how freely available open data can be used to facilitate these two ideals. 4) To show how mobile technology can be used to facilitate these two ideals.
ClinicalCodes.org: An online repository of clinical code lists for primary ca...David Springate
This document discusses ClinicalCodes.org, an online repository for clinical code lists used in primary care database research. It outlines issues with a lack of published code lists, such as inability to validate or replicate studies and difficulty comparing studies over time as condition definitions change. ClinicalCodes.org aims to address these issues by providing a central location for researchers to upload, download, and archive code lists. This would improve research quality and allow other researchers to build upon previous work in a standardized way. Motivations for researchers to upload their code lists include validation of their work, increased citations, and a requirement by journals and funders for transparent and accessible code lists.
Pharmacovigilance is the science of detecting, assessing, understanding, and preventing adverse effects or any drug-related problems. The goals of pharmacovigilance are to improve patient safety, assess benefits and risks of medicines, and ensure their safe use. It involves collecting reports of adverse drug reactions (ADRs) from healthcare professionals and patients and analyzing the data to identify new safety issues and risk factors. Pharmacovigilance relies on spontaneous reporting systems but also uses active surveillance methods like cohort studies and registries to monitor drug safety post-marketing. It is a shared responsibility between drug regulators, healthcare professionals, and pharmaceutical companies to help prevent drug-related harm and protect public health.
2016 03-17 Health Valley Event 2016, Alain van GoolAlain van Gool
Sharing thoughts during the session Personalized Medicine at the Health Valley Event 2016, which again was a great event with 1100+ health care innovators !
2017 03-07 World Economic Forum - Dutch topsector Life Science Health, The Ha...Alain van Gool
The document discusses the Netherlands' approach to personalized medicine and health research. It outlines key principles of precision medicine including targeting the right drug, dose, and time for each patient. It also describes the Netherlands' national infrastructure supporting personalized medicine research through biobanks, clinical records, and other data sources. Mass spectrometry is highlighted as a technique enabling discovery of new glycoprotein biomarkers from human plasma samples.
2016 09-21 symposium Opening the BBMRI genomics infrastructure in The Netherl...Alain van Gool
Keynote lecture for the BBMRI genomics community at this BBMRI symposium, outlining my perspective on personalized medicine and health, and the various activities within The Netherlands to shape the healthRI.
2016 11-15 Lygature partnership meetup, Utrecht, Alain van GoolAlain van Gool
Contribution to the opening of the Joint Innovation Mile in the Beatrix building in Utrecht, home of the offices of Lygature, HealthRI, BBMRI-NL and others to follow.
2016 09-08 Copenhagen Bioscience Lecture, Alain van GoolAlain van Gool
On invitation of the Novo Nordisck Foundation, an interactive story on personalized healthcare, biomarkers and innovation in proteomics for a group of enthousiastic young scientists.
2021 03-25 11th World Clinical Biomarkers & Companion Diagnostics, Alain van ...Alain van Gool
Closing keynote of a 3-day conference on clinical biomarkers and companion diagnostics, organised by Hanson Wade, outlining the power of omics approaches in healthcare and translation of inovations to impact.
2020 08-28 SensUs Event 2020 keynote, Eindhoven, Alain van GoolAlain van Gool
Closing keynote for international students participating in the SensUs Event 2020, where they designed and created a novel sensor for drug level monitoring in epilepsy treatment. Lecture outlined innovations in biomarkers in personalized health(care).
2020 09-07 European Center Pharmaceutical Medicine course Biomarkers, Basel, ...Alain van Gool
Tutorial lecture on biomarkers for pharmaceutical industry R&D professionals, outlining status, potential and challenges of biomarkers in pharma, clinic and society.
2015 12-09 Opening Radboud Translational Medicine, Nijmegen, Alain van GoolAlain van Gool
Keynote opening lecture at the grand opening of our new cyclotron facility, embedded in Radboud Translational Medicine and part of our Radboudumc Technology Centers. See http://www.radboudtranslationalmedicine.nl/nl/ for details.
2019 06-19 Dutch association for clinical chemistry and laboratory medicine -...Alain van Gool
Sharing my views on how X-omics biomarker analyses through next gen sequencing and mass spectrometry will change the landscape of diagnostics and clinical chemistry in the near future.
2020 02-10 European Center Pharmaceutical Medicine course - biomarkers, Basel...Alain van Gool
This document discusses biomarkers and personalized healthcare. It begins with an overview of biomarkers in the pharmaceutical industry and how they are used from drug discovery through clinical trials. It then discusses biomarkers in academic research and healthcare, and how emerging digital biomarkers could enable personalized health monitoring. The presentation identifies some translational innovation gaps, and concludes with an outlook on how biomarkers and multi-omics approaches will continue to advance personalized diagnosis and therapies.
2015 07-03 Nanonext NL Alain van Gool, AmsterdamAlain van Gool
The document discusses implementing personalized healthcare through measuring biomarkers. It notes that while many biomarkers have been discovered, few are validated and applied in diagnostic tests. There is also a gap in translating biomarkers into point-of-care applications. The document advocates for open innovation networks to help validate biomarkers across multiple centers and standardize clinical applications. Ultimately, the focus of personalized healthcare should be on the patient by providing individualized follow-up based on their molecular and clinical measurements.
2018 03-01 International Conference on Perspectives in Precision Medicine, Co...Alain van Gool
This keynote lecture reviews the historical and ongoing investments in public-private partnerships related to precision medicine and the related technological infrastructures. It served as example to the Danish community how translational biomarkers in precision medicine can be organised, as basis for further collaboration between Denmark and Netherlands.
2021 06-14 EATRIS-Plus summer school, Alain van GoolAlain van Gool
Introductory lecture for the 100 participant summer school of the EATRIS-Plus project, outlining personalized medicine, biomarker and multi-omics strategies and use cases.
2018 11-26 KNAW-AcTI symposium Personalized Health, Amsterdam, Alain van GoolAlain van Gool
Lecture at a citizen discussion evening, reviewing the promises and (ethical) considerations of technology developments to support personalized health, organised by the Royal Academy of Sciences and the Netherlands Academy of Technology and Innovation.
2019 10-14 2nd Int Congress on Precision Medicine, Munich, Alain van GoolAlain van Gool
Opening lecture at the 2nd International Congress on Precision Medicine in Munich, outlining progress in omics-based biomarkers for rare diseases, biomarker innovation gaps and multi-partner initiatives to bridge those gaps to applications. Also reviewed the highlights of our recently published Handbook of Biomarkers and Precision Medicine.
2015 09-14 Precision Medicine 2015, London, Alain van GoolAlain van Gool
Outline of my view hoe personalized health(care) is more than just targeted medicines, also including personal motivation and actions towards disease prevention. It also outlines 4 key factors that should be in order for optimal personalized health(care): 1. start with patients first, 2. Accelerate translation research to application, 3. Copy best practice, 4. Spread the word.
From Bits to Bedside: Translating Big Data into Precision Medicine and Digita...Dexter Hadley
Lecture Objectives:
1) To use examples from my research to define and introduce the ideals of precision medicine and digital health. 2) To introduce how large scale population-wide analysis of data can be used to facilitate these two ideals. 3) To introduce how freely available open data can be used to facilitate these two ideals. 4) To show how mobile technology can be used to facilitate these two ideals.
ClinicalCodes.org: An online repository of clinical code lists for primary ca...David Springate
This document discusses ClinicalCodes.org, an online repository for clinical code lists used in primary care database research. It outlines issues with a lack of published code lists, such as inability to validate or replicate studies and difficulty comparing studies over time as condition definitions change. ClinicalCodes.org aims to address these issues by providing a central location for researchers to upload, download, and archive code lists. This would improve research quality and allow other researchers to build upon previous work in a standardized way. Motivations for researchers to upload their code lists include validation of their work, increased citations, and a requirement by journals and funders for transparent and accessible code lists.
Pharmacovigilance is the science of detecting, assessing, understanding, and preventing adverse effects or any drug-related problems. The goals of pharmacovigilance are to improve patient safety, assess benefits and risks of medicines, and ensure their safe use. It involves collecting reports of adverse drug reactions (ADRs) from healthcare professionals and patients and analyzing the data to identify new safety issues and risk factors. Pharmacovigilance relies on spontaneous reporting systems but also uses active surveillance methods like cohort studies and registries to monitor drug safety post-marketing. It is a shared responsibility between drug regulators, healthcare professionals, and pharmaceutical companies to help prevent drug-related harm and protect public health.
2016 03-17 Health Valley Event 2016, Alain van GoolAlain van Gool
Sharing thoughts during the session Personalized Medicine at the Health Valley Event 2016, which again was a great event with 1100+ health care innovators !
2017 03-07 World Economic Forum - Dutch topsector Life Science Health, The Ha...Alain van Gool
The document discusses the Netherlands' approach to personalized medicine and health research. It outlines key principles of precision medicine including targeting the right drug, dose, and time for each patient. It also describes the Netherlands' national infrastructure supporting personalized medicine research through biobanks, clinical records, and other data sources. Mass spectrometry is highlighted as a technique enabling discovery of new glycoprotein biomarkers from human plasma samples.
Strategic planning involves defining a laboratory's strategy to withstand competitive forces by understanding industry structure, competitors' strengths and weaknesses, identifying a unique market position, and focusing on growth. It contrasts with operations management which efficiently uses resources. A laboratory should understand its industry's concentration, barriers to entry/exit, separate roles of payors/purchasers/beneficiaries, economies of scale, and powerful buyers/sellers to strategically position itself. Common positions include outpatient-centered, reference-centered, and hospital-centered testing. Strategies can fail due to straddling multiple positions, pursuing growth that does not fit capabilities, or exhibiting hubris. SWOT and competitor analyses help develop and implement effective strategies.
Reverse Innovation offers the unique opportunity to develop innovativ solutions for exponentially growing problems/markets in an often less regulated (emerging) markets leapfrogging incremental product and market developments in established markets.
InnVentis provides precision medicine through analyzing personal molecular profiles derived from multi-omics data and the internet of things to recommend diets and supplements personalized to each individual's daily schedule.
The document describes a client acquisition program called Right Financial Advisor. It is a web-based matching program that connects individual investors to vetted financial advisors. It aims to help advisors clone their best A and B clients while pruning poorer C and D clients. The program uses personality and financial needs questions to make better matches than competitors that rely solely on location or assets. It markets itself online and on social media to acquire new investors and advisors. Investors pay $35 to join while advisors pay $200 per month for unlimited introductions.
The document discusses the convergence of traditional TV and digital video. It notes that while digital video spending and viewership has grown significantly, it still accounts for only about 10% of the total US TV and video market. Several factors are driving the convergence of traditional and digital media, including the proliferation of internet-connected devices, the rise of over-the-top streaming services, and major companies in tech and media investing heavily in original digital video content and making acquisitions in the space. The document argues that players in the TV and video ecosystem should focus on serving the entire market rather than just digital or traditional segments.
This document provides a lighting study for a community library project. It analyzes the daylight factor and artificial lighting needs for two areas: the lobby/cafeteria and art gallery. The cafeteria achieves a daylight factor of 7.1% while the art gallery achieves 3.49%. Artificial lighting calculations and layouts are also provided for the reading area and children's area to meet the 300-500 lux illumination levels required by standards. The reading area requires 56 light fixtures controlled by 3 switches, while the children's area needs 25 fixtures controlled by 2 switches.
The document analyzes and summarizes three fashion/beauty websites - Vogue, Accent, and Bazaar - in order to inform the design of a new website aimed at teenagers. For Vogue, it notes the simple and mature design with little color. For Accent, it observes the use of color and images to appeal to a younger audience. For Bazaar, it sees a more mature look through use of darker colors and many images over text. Overall, the document examines design elements like layout, fonts, and images across the three websites to understand how to create a professional-looking site that will appeal to its target teenage demographic.
state_of_app_downloads_and_monetization_2015_globalTuan Anh Nguyen
The document discusses key metrics and trends related to global app installs and monetization based on data from InMobi's mobile advertising platform. Some of the main findings include:
- China remained the leading market for app installs globally. Shopping and lifestyle apps saw strong growth worldwide.
- The gap between Android and iOS installs narrowed in Asia Pacific as iOS gained popularity. Install costs were generally higher for iOS compared to Android.
- Mature markets like the US and South Korea had higher eCPMs, indicating users were more willing to spend via mobile. Education apps earned developers the highest eCPMs on average.
- Markets with higher smartphone penetration tended to have lower per capita installs but higher
Targeted Threat (APT) Defense for Applications Featuring pxGrid: a deep diveCisco DevNet
A session in the DevNet Zone at Cisco Live, Berlin. Targeted Attacks, which the media refers to as APTs, are threats that must be addressed by any organization requiring networked computers to do business. In this session we will go over the run book techniques used by these threat actors and then go over strategies for mitigating those attacks. In this session we will focus on the concepts that developers of network applications need to be aware of to mitigate these styles of attacks and techniques to use. To finish off, we will delve into pxGrid and what it can offer to break these APT style attack playbooks. Backgrounder: We obtained knowledge of these run book techniques from trusted advisors, peers in the industry and from our own observations. Our own observations included information from our CSIRT, our security products in the field as well as our internal phishing awareness campaign. After studying these techniques we devised strategies to mitigate them. Those strategies were then tested and deployed throughout our ecosystem. The Cisco CSDL initiative and ACT2 chips will also be techniques and tools highlighted in this session.
2014 08-20 Radboudumc-Health Valley-LSH: Personalized Healthcare through inte...Alain van Gool
1) Personalized healthcare aims to stratify patients based on multi-level diagnoses and patient preferences to select personalized therapies.
2) Radboud University Medical Center is working to advance personalized healthcare through various technology centers that integrate omics data like genomics, glycomics, and metabolomics.
3) Key goals include developing diagnostic tests and personalized therapies through collaborative projects, working with innovators and spin-off companies, and integrating data and technologies.
DEVNET-1148 Leveraging Cisco OpenStack Private Cloud for DevelopersCisco DevNet
The document discusses developing applications on Cisco OpenStack Private Cloud. It describes setting up a development environment using CoreOS, Docker, Gitlab, Jenkins, Slack, and Ansible. The environment automates the deployment of load balancers, web servers, and other application components from source code commits using continuous integration and continuous delivery practices. Jenkins is configured to build Docker containers from code commits and deploy them to instances in the private cloud.
The document summarizes the design choices made for three magazine covers and a fashion spread for a magazine targeted at teenagers. For each element, the designer considered how to represent teenagers stylishly while incorporating the planned cover lines. Across all elements, the designer used a consistent color scheme of red, black and white and font to tie the magazine and fashion spread together visually. The covers feature models in poses and outfits relevant to the planned cover lines. For the fashion spread, the designer chose outfits and photos that fit an overall "dolls" theme and used matching makeup, hair, and photo effects to achieve flow across the spread.
2015 05-20 Radboudumc REshape breakfast meeting Alain van GoolAlain van Gool
This document discusses biomarkers in personalized healthcare and moving beyond targeted medicine. It provides an overview of the speaker's background and experience in academia, pharmaceutical industry, and medical school related to biomarkers, omics technologies, and personalized healthcare. It then discusses the exponential developments in biomarker technologies, the need for a systems biology view in personalized healthcare, and translation challenges in bridging the gap between biomarkers and personalized interventions for patients.
Celador is a small British production company that operates on a project-by-project basis, contracting freelance staff for each production. It was originally owned by Complete Communication but was sold in 2006. In 2004, Celador sued Disney for unpaid profits from screenings of Who Wants to be a Millionaire? in the US. Notable films produced include Dirty Pretty Things, Separate Lies, The Descent, and Slumdog Millionaire, often through co-productions with other small companies. Though much smaller than major Hollywood studios like 20th Century Fox, Celador has found success competing with larger films.
2016 05-24 Kick-off The Danish Biomarker Network, Copenhagen, Alain van GoolAlain van Gool
Keynote lecture given at the kick-off of The Danish Biomarker Network in Copenhagen for a great audience of enthousiastic patients, biotech/pharma developers and ICT experts.
2015 10-06 Building Bridges Biomarker symposium FIMM Helsinki, Alain van GoolAlain van Gool
A unique honour and opportunity to give a 1.5 hour lecture to young biomarker scientists to introduce biomarkers and their importance in translational medicine and personalized healthcare.
2013-04-23 Top Institute Pharma Spring meeting, UtrechtAlain van Gool
Companion diagnostics use biomarkers as diagnostic tools to identify patients who will respond well to specific drug therapies. The presentation discusses the increasing use of companion diagnostics in oncology drug development and clinical trials. It provides examples of biomarkers used to identify patients with melanoma who will benefit from BRAF inhibitor drugs. While some biomarkers like BRAFV600E mutations are useful targets, tumor heterogeneity poses a challenge for companion diagnostics. The presentation calls for improving the pipeline for validating biomarkers and developing them into clinical diagnostic tests.
2014 07-08 Selectbio Biomarkers 2014, CambridgeAlain van Gool
The document discusses biomarkers in personalized healthcare from discovery to clinical diagnostics, providing an overview of the speaker's experience in academia, pharmaceutical industry, and applied research focusing on biomarkers and omics technologies. It also describes the Radboud University Medical Center's focus on personalized healthcare through its technology centers and biomarker research on conditions like metabolic syndrome. The discussion emphasizes how biomarkers are evolving from diagnosis to tools that enable personalized and participatory healthcare approaches.
2015 04-13 Pharma Nutrition 2015 Philadelphia Alain van GoolAlain van Gool
Keynote lecture at the Pharma-Nutrition 2015 conference, outline global paradigm shifts and activities in pharma, personalized healthcare and pharmanutrition combination therapies.
2014 02-24 Oxford Global biomarker congress, ManchesterAlain van Gool
This document summarizes a presentation given by Alain van Gool on biomarkers in a changing world. It discusses the shift from personalized medicine to personalized healthcare, which takes a more holistic systems view of an individual. It also notes disruptive technologies that can accelerate biomarker development and the need to translate biomarkers into useful tools. Throughout, it provides examples of challenges like tumor heterogeneity and factors beyond genetics that influence disease and response to treatment.
Lecture describing workflows and case studies from the Translational Metabolic Laboratory @Radboudumc how to translate x-omics biomarker signatures to clinical implementation. I also highlighted new developments to join forces in the Netherlands X-omics Initiative, United for Metabolic Disease and events/book launches in the next months.
2015 01-06 Oudejaarssymposium Personalized Healthcare, GroningenAlain van Gool
Personalized healthcare is moving beyond just targeted medicine to become more patient-centered. Biomarkers are playing an evolving role, from diagnosis to translational medicine to personalized healthcare. Radboud University Medical Center aims to have a significant impact on healthcare through their focus on personalized healthcare and including the patient as a partner. Their integrated translational research and diagnostic laboratory develops biomarkers through various omics technologies for personalized diagnosis and treatment.
2015 11-26 ODDP2015 Course Oncology Drug Development, Amsterdam, Alain van GoolAlain van Gool
This document describes the development of biomarkers to support targeted cancer therapies, using the case study of biomarkers for BRAF inhibitors in melanoma. Key points:
- The BRAFV600E mutation causes constitutive activation of the ERK pathway and is prevalent in melanoma, making it a promising drug target.
- siRNA and RAF inhibitor compounds were shown to inhibit the ERK pathway and cell proliferation in BRAF mutant cell lines but not wildtype lines, validating BRAF mutation as a predictive biomarker.
- Further optimization of RAF inhibitors focused on potency, selectivity against other kinases, and efficacy in mouse models to support clinical development.
- There remains a need to identify soluble protein biomarkers in blood
2017 05-18 Radboudumc Information Management Inspiration Point, Nijmegen, Ala...Alain van Gool
The document discusses the validation of interleukin-8 (IL-8) as a biomarker for melanoma. A study was conducted using 59 melanoma tumor tissue samples and matching serum and plasma to validate that IL-8 is elevated in melanoma. However, the results were inconsistent, as IL-8 protein levels appeared sensitive to freeze-thawing of samples. The author advocates for increasing the quality rather than quantity of biomarker research through improved collaboration to ensure better data and validation.
Pharma-Nutrition: a pharma perspective. View how the pharmaceutical drug development model can and should be combined with the nutrition field to optimally implement personalized healthcare.
The document discusses biomarkers in oncology from cells to systems. It notes that while many biomarkers are discovered, few progress beyond initial publication to clinical validation and diagnostic tests. Reasons for this innovation gap include a lack of integrated biomarker research and development pipelines and challenges in organizing multi-lab validation studies. The talk emphasizes embracing novel omics technologies, considering tumor cells as part of a biological system, and focusing on biomarker validation to address this gap. It provides examples of using mRNA expression profiling and systems-level approaches to stratify and characterize tumors.
2019 02-21 Oxford Global 14th Biomarker Congress, Manchester, Alain van GoolAlain van Gool
1. Professor Alain van Gool presented on using clinical x-omics to drive personalized healthcare.
2. He described case studies where combining different omic approaches like genomics, metabolomics, and glycomics led to novel disease mechanisms and therapies for rare genetic diseases.
3. Van Gool advocated for increased collaboration and standardization of omic technologies to advance precision medicine and bring clinical multi-omics to higher diagnostic and therapeutic levels.
2012 19-11 EC DG R&I biomarker lecture, BrusselsAlain van Gool
Invited lecture for the European Commission, Directorate General Research & Innovation, to outline developments and needs in biomarker research for biomedical applications.
The dream of any physician and consequently every patient is to receive the right treatment in the right time with cost effectiveness. To achieve this goal, the 3 pillars: evidence based medicine, clinical research innovation & resources utilization should be integrated efficiently.
In this presentation, I'll try to comprehensively review the following:
1- How are we used to perform clinical trials in Oncology?
2- Does it fits in today’s needs?
3- Integration of biology knowledge in shaping drug development
4- New Clinical trial designs “Can they offer solution for accelerating drug development?”
5- The supporting infrastructure role in clinical trial execution
2014 09-25 MipTec Europe's Drug Discovery eventAlain van Gool
This document discusses biomarkers in personalized healthcare and medicine. It is presented by Professor Alain van Gool, who has experience in both academia and the pharmaceutical industry researching biomarkers and personalized health. The presentation discusses the evolving role of biomarkers from diagnosis to personalized healthcare and medicine. It emphasizes the need for a systems approach using multi-omics data to develop personalized diagnostics and combination therapies for complex diseases like diabetes. Personalized healthcare is about tailoring treatment to each individual based on their molecular profiling and preferences.
2016 11-17 Oncology by design 2016 course, Amsterdam, Alain van GoolAlain van Gool
Lecture on the the role of biomarkers in oncology drug development, given to a group of pharmaceutical industry specialists, in tandem with a lecture on oncology companion diagnostics given by Martina Kaufmann.
Please share this webinar with anyone who may be interested!
Watch all our webinars: https://www.youtube.com/playlist?list=PL4dDQscmFYu_ezxuxnAE61hx4JlqAKXpR
Cancer care is increasingly tailored to individual patients, who can undergo genetic or biomarker testing soon after diagnosis, to determine which treatments have the best chance of shrinking or eliminating tumours.
In this webinar, a pathologist and clinical oncologist discuss:
● how they are using these new tests,
● how they communicate results and treatment options to patients and caregivers, and
● how patients can be better informed on the kinds of tests that are in development or in use across Canada
View the video: https://youtu.be/_Wai_uMQKEQ
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2023-11-14 Biomarkers Europe 2023, Berlin, Alain van Gool.pdfAlain van Gool
Lecture at the Biomarkers Europe 2023 conference for an audience of pharma scientists and omics/data solution providers. I outlined several initiatives of potential interest and discussed development of our sensitive personalized clinical biomarker test for minimal residual disease monitoring in multiple myeloma.
2023-11-09 HealthRI Biobanking day_Amsterdam_Alain van Gool.pdfAlain van Gool
Examples of lessons learned in Omics-based biomarker studies from myself and colleagues in X-omics and EATRIS, for an audience of biobankers, researchers and diagnostic/clinical chemistry experts.
2023-04-20 EATRIS-Plus Summerschool, Lisbon, Alain van GoolAlain van Gool
Closing keynote lecture at the EATRIS-Plus summerschool on personalised medicine, outlining developments, opportunities, challenges and recommendations to do next in this exciting era of personalised medicine.
2022-11-23 DTL Future of data-driven life sciences, Utrecht, Alain van Gool.pdfAlain van Gool
A pitch on directions to improve experimental reproducibility, illustrated by examples of past experiences. I made the plee to move from 'Proudly invented here' to 'Proudly copyied from', to re-use each other's eperiences in successes and failures.
2022-10-12 The future of population health_Alain van Gool.pdfAlain van Gool
1) Exponential developments in omics technologies like genomics, proteomics, and metabolomics are driving more personalized approaches to healthcare.
2) Mass spectrometry methods have been developed to sensitively detect minimal residual disease in multiple myeloma patients from plasma samples, allowing for dynamic monitoring and earlier detection of relapse compared to traditional methods.
3) Large-scale multi-omics studies incorporating data from various sources can provide a more holistic view of health and disease at both the individual and population levels, supporting personalized prevention and treatment approaches.
2022-09-08 ECPM Digital Biomarkers and AI, Basel, Alain van Gool.pdfAlain van Gool
Lecture for 150 pharma professionals to outline the potentials and things-to-do with digital biomarkers, as part of a ECPM training on digitization and AI in drug development.
2022-04-14 EuroMedLab, Munich, Alain van GoolAlain van Gool
Keynote lecture at the EuroMedLab 2021 providing an audience of clinical chemists and laboratory medicine scientists with advancements of multi-omics applications in personalized healthcare, and challenges that we need to solve as translational scientists.
2021 12-10 Amalia Science Day, Nijmegen, Alain van GoolAlain van Gool
This document discusses the use of omics technologies like genomics, proteomics, and glycoproteomics in pediatric healthcare. Specifically, it describes a study that used glycoproteomics to analyze blood samples from children with febrile illness to distinguish between viral and bacterial infections. The analysis identified glycoprotein biomarkers that could accurately classify 70-80% of samples as viral or bacterial. Integrating multiple omics data through machine learning approaches may provide a more comprehensive understanding of diseases and lead to personalized diagnosis and treatment.
2019 09-23 COST CliniMARK summerschool, Spetses, Alain van GoolAlain van Gool
Opening lecture of the COST CliniMARK summer school 'Approaches for Biomarker Discovery and Validation'. Extensive introduction in biomarker approached used in pharmaceutical industry, academic research and clinical care, and society, combined with review of biomarker innovation gaps and outlook.
2019 03-14 Health Valley Event 2019, Nijmegen, Alain van GoolAlain van Gool
Lecture on innovations in personalized healthcare using an integrated X-omics approach towards personalized diagnostics, as part of the regional ambitious TopFit program.
2018 12-07 Danone-Nutricia Precision Nutrition Forum, Utrecht, Alain van GoolAlain van Gool
1. The document discusses innovations in personalized health and healthcare using various omics technologies and big data. It highlights developments in genomics, metabolomics, glycomics, and proteomics that enable personalized diagnosis and therapy.
2. Several examples are provided of how multi-omics approaches combined with whole exome sequencing can identify new disease mechanisms and biomarkers for precision medicine in genetic disorders.
3. The development of systems approaches that integrate multi-level omics data, environment, and lifestyle factors is needed to create personalized data-driven tools to monitor health and provide customized recommendations.
2018 12-04 CHAINS X-omics workshop lecture, Veldhoven, Alain van GoolAlain van Gool
Introducing the innovations we plan to do in the Netherlands X-omics Initative, together with other X-omics consortium members, at a dedicated X-omics workshop at the annual congres of the Netherlands Chemistry society.
2018 11-28 SAB Interreg BIC project Baltic Sea Region, Copenhagen, Alain van ...Alain van Gool
Overview of the current challenges in biomarker commercialisation, to kick off the scientific advisory board meeting with the multidisciplinary Interreg BIC project team.
2018 11-02 Healthy Brain Cohort progress meeting, Nijmegen, Alain van GoolAlain van Gool
Highlights and anecdotes from my experiences in interdisciplinary research in big data for personalized healthcare whilst working in Europe, USA and Singapore
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
One health condition that is becoming more common day by day is diabetes.
According to research conducted by the National Family Health Survey of India, diabetic cases show a projection which might increase to 10.4% by 2030.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
Hiranandani Hospital in Powai, Mumbai, is a premier healthcare institution that has been serving the community with exceptional medical care since its establishment. As a part of the renowned Hiranandani Group, the hospital is committed to delivering world-class healthcare services across a wide range of specialties, including kidney transplantation. With its state-of-the-art facilities, advanced medical technology, and a team of highly skilled healthcare professionals, Hiranandani Hospital has earned a reputation as a trusted name in the healthcare industry. The hospital's patient-centric approach, coupled with its focus on innovation and excellence, ensures that patients receive the highest standard of care in a compassionate and supportive environment.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
REGULATION FOR COMBINATION PRODUCTS AND MEDICAL DEVICES.pptx
2016-02-01 ECPM Basel Alain van Gool
1. Biomarkers in
Personalized Healthcare
Professor of Personalized Healthcare
Head Radboud Center for Proteomics, Glycomics
and Metabolomics
Coordinator Radboud Technology Centers
Senior Scientist Integrator Biomarkers
Prof Alain van Gool
European Center Pharmaceutical Medicine course
Pharmacenter Basel, February 1-3, 2016
2. My background
8 years academia (NL, UK)
(molecular mechanisms of disease)
13 years pharma (EU, USA, Asia)
(biomarkers, Omics)
4 years med school (NL)
(personalized healthcare, Omics, biomarkers)
4 years applied research institute (NL, EU)
(biomarkers, personalized health, nutrition)
1991-1996
(PhD)
1996-1998
(post-doc)
2009-2012
(visiting prof)
1999-2007 2007-2009 2009-2011
2011-now
2011-now (prof)
2
Biomarkers, Molecular Profiling, Translational Medicine, Personalized Healthcare
Metabolic, Oncology, Neuroscience, Cardiovascular, Reproductive Medicine
Alain van Gool, ECPM course, Basel, 1 Feb 2016
3. The pharmaceutical R&D phases (since 2000)
• A rational and step-wise approach
• ‘reverse pharmacology’
• Cleaner and more specific drugs
3 Alain van Gool, ECPM course, Basel, 1 Feb 2016
4. Translational medicine in pharma
Basic Research
In Vitro Studies
Target Validation
Animal Models
Phase I and Phase II
-PoC- Studies
Phase III Studies
Clinical Research
Forward TranslationForward Translation
Reverse TranslationReverse Translation
(View drug development
as customer)
(Feed back clinical needs
and samples)
[van Gool et al, Drug Disc. Today 2010]
4 Alain van Gool, ECPM course, Basel, 1 Feb 2016
5. Biopsies
Tissues
Translational medicine in pharma
etc
Monkey
Pig
etc
Rabbit
Mice
Ex vivo
Rodents
DogTissues
Cell lines
Primary
cells
Diseased
human
Healthy
human
RatCellsHTS
(solution)
assays
Cell lines
• High attrition from Research to Development (90%)
• Frequent crossing of systems barriers during drug development
• High need for translational models and biomarkers to bridge R&D and
determine drug exposure, efficacy and safety
5 Alain van Gool, ECPM course, Basel, 1 Feb 2016
6. Limited view on complex systems from the outside
Source: Gary Larson
Animal models Patient-related outcomes
Source: National University Hospital Singapore
6 Alain van Gool, ECPM course, Basel, 1 Feb 2016
7. Key is to have a good view inside
High need for molecular tools that allow a look into the black box
and improve disease management: biomarkers
Drug exposure ?
Diagnosis ?
Cross-species differences ?
Patient classification ?
Prognosis ?
Target engagement ?
Modulation of mechanism ?
Off-target drug effects ?
Treatment Phenotype
Mechanism ?
Other (latent) diseases ?
Person
7 Alain van Gool, ECPM course, Basel, 1 Feb 2016
8. Biomarkers
{Biomarkers definition working group, 2001 }
Definition: ‘a characteristic that is objectively measured and evaluated as
an indicator of normal biological processes, pathogenic processes, or
pharmacologic responses to a therapeutic intervention’
Or ‘Whatever works in adding value’
Molecular biomarkers provide a molecular impression of a biological system
(cell, animal, human)
Biomarkers can be various sorts of data, or combinations thereof
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
8 Alain van Gool, ECPM course, Basel, 1 Feb 2016
9. Evolving role of biomarkers
• From Diagnosis
• To Translational Medicine
• To Personalized/Stratified/Precision Medicine
• To Personalized Health(care)
9 Alain van Gool, ECPM course, Basel, 1 Feb 2016
10. Biomarker-based translational medicine
• Does the compound get to the site of action?
• Does the compound cause its intended
pharmacological/ functional effects?
• Does the compound have beneficial effects on disease
or clinical pathophysiology?
• What is the therapeutic window (how safe is the drug)?
• How do sources of variability in drug response in target
population affect efficacy and safety?
Lead
Optimization
Exploratory
Development PoC
Lead
Discovery
Target
Discovery
Exposure ?
Mechanism ?
Efficacy ?
Safety ?
Responders ?
{van Gool et al, Drug Disc Today 2010}
{Kumar, van Gool, RSC biomarkers, 2013}
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
One strategy
10
12. Biomarker strategy: Data-driven decisions
To be made during testing of drug in preclinical and clinical disease models:
Target engagement? Effect on disease?
yes yes !
no no
• No need to test current
drug in large clinical trial
• Need to identify a more
potent drug
• Concept may still be
correct
• Concept was not correct
• Abandon approach
• Proof-of-Concept
• Proceed to full
clinical
development
“Stop early, stop cheap”
“More shots on goal”
12
{Kumar, van Gool, RSC biomarkers, 2013}
13. Rational selection of best targets and drugs works
The 5R’s assessment:
• Right Target
• Right Tissue
• Right Safety
• Right Patients
• Right Commercial Potential
13
14. Adopt rational target selection in pharma research
CarTarDis = Cardiovascular Target Discovery
Public-private partnership, 13 partners, 8 countries, project budget 8.0M Eur
Started 1 Oct 2013 for 4 years
Adopting AstraZeneca’s 5R strategy in drug target selection
(Coordinator)
CarTarDis.eu
14
15. Successes of drug development
Antibiotics Vaccins
Reproductive medicine Oncology
15 Alain van Gool, ECPM course, Basel, 1 Feb 2016
16. Source: John Arrowsmith: Nature Reviews Drug Discovery 2011
• Success rates of clinical proof-of-concept have dropped from 28% to 18%
• Insufficient efficacy as the most frequent reason
• Targeted therapy through Personalized Medicine may be the solution
• Patient selection using companion diagnostics
A need for Personalized Medicine
(Analysis of 108 failures in phase II)
Reason for failure Therapeutic area
16 Alain van Gool, ECPM course, Basel, 1 Feb 2016
17. {Source: Chakma. Journal of Young Investigators. 2009}
Principle of Personalized/Precision/Targeted Medicine
17 Alain van Gool, ECPM course, Basel, 1 Feb 2016
18. Case study: B-RAF mutations and melanoma
{Miller and Mihm,
2006}
18 Alain van Gool, ECPM course, Basel, 1 Feb 2016
19. Mechanism of pathophysiology in BRAF mutated tumors
V600E
Kinase domain
{Roberts and Der, 2007}
• B-RAFV600E mutation: constitutively active kinase, oncogenic addiction
• Overactivate ERK pathway drives cell proliferation
• RAF inhibitors shown to block growth of tumors with B-RAFV600E mutation
• Prevalence of B-RAFV600E is base for patient selection:
• Melanoma (60%), colon (15%), ovarian (30%), thyroid (30%) cancer
19 Alain van Gool, ECPM course, Basel, 1 Feb 2016
20. Clinical efficacy of Vemurafenib (PLX-4032, Zelboraf)
Key biomarkers:
Stratification: BRAFV600E mutation
Mechanism: P-ERK
Cyclin-D1
Efficacy: Ki-67
18FDG-PET, CT
Clinical endpoint: progression-free survival (%)
{Source: Flaherty et al, NEJM 2010}{Source: Chapman et al, NEJM 2011}
20 Alain van Gool, ECPM course, Basel, 1 Feb 2016
21. Development of Vemurafenib (Zelboraf)
{Source: Davis M J , Schlessinger J J Cell Biol 2012}
21 Alain van Gool, ECPM course, Basel, 1 Feb 2016
27. Emerging protein biomarkers
27
Current diagnostic protein assays:
• Mostly protein abundance
Emerging:
• Post-translational modifications
• Ratio protein isoforms
• Protein complexes
Alain van Gool, ECPM course, Basel, 1 Feb 2016
29. Discovering new glycoprotein biomarkers
• 1D LC-MS/MS glycoproteomics in plasma
• Detection of 100K features in one scan
• ~20.000 unique deconvoluted monoisotopic masses per single analysis
(> 50% are glycopeptides)
500
1000
1500
2000
m/z
5 10 15 20 25 30 35 40 Time [min]
Proof of principle study:
29
{Hans Wessels, Monique van Scherpenzeel, Dirk Lefeber, Alain van Gool, unpubl}
Alain van Gool, ECPM course, Basel, 1 Feb 2016
30. New diagnostic glycoprotein biomarker
• Rare metabolic disease cases (liver disease and dilated cardiomyopathy)
• Combination glycoproteomics and exome sequencing
• Outcome 1: Explanation of disease
• Outcome 2: Dietary intervention as succesful personalized therapy
• Outcome 3: Glycoprofile transferrin developed and applied as diagnostic test
{Tegtmeyer et al, NEJM 370;6: 533 (2014)}
Genomics Glycomics Metabolomics
{Monique van Scherpenzeel, Dirk Lefeber}
30 Alain van Gool, ECPM course, Basel, 1 Feb 2016
34. healthy disease disease +
treatment
Interpret data with self-normalisation
Subgroups
100%
Normalisation of responders
34 Alain van Gool, ECPM course, Basel, 1 Feb 2016
36. Biomarker innovation gaps: some numbers
5 biomarkers/
working day
1 biomarker/
1-3 years
1 biomarker/
3-10 years
?
Eg Biomarkers in time: Prostate cancer
May 2011: n= 2,231 biomarkers
Nov 2012: n= 6,562 biomarkers
Oct 2013: n= 8,358 biomarkers
Nov 2014: n= 10,350 biomarkers
Oct 2015: n = 11,856 biomarkers
Discovery Clinical
validation/confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2
Gap 3
36 Alain van Gool, ECPM course, Basel, 1 Feb 2016
37. Reasons for biomarker innovation gap
• Not one integrated pipeline of biomarker R&D
• Publication pressure towards high impact papers
• Lack of interest and funding for confirmatory biomarker studies
• Hard to organize multi-lab studies
• Biology is complex on organism level
• Data cannot be reproduced
• Bias towards extreme results
• Biomarker variability
• …
{Source: John Ioannidis, JAMA 2011}
{Source: Prinz, Schlange, Asadullah, Nat Rev Drug Disc 2011}
37 Alain van Gool, ECPM course, Basel, 1 Feb 2016
38. Identification of ERK pathway biomarkers
• Pharmacogenomics A375
melanoma cells
• Study effect of 4 RAF, 2 MEK,
1 ERK inhibitors
• Select biomarkers based on
profile and function
RAFi #4
MEKi #1
MEKi #2
RAFi #3
RAFi #1
RAFi #2
ERKi #1
RAFi #4
MEKi #1
MEKi #2
RAFi #3
RAFi #1
RAFi #2
ERKi #1
RAFi #4
MEKi #1
MEKi #2
RAFi #3
RAFi #1
RAFi #2
ERKi #1
RAFi#1
RAFi#2
RAFi#3
RAFi#4
MEKi#1
MEKi#2
ERKi#1
RAFi#1
RAFi#2
RAFi#3
RAFi#4
MEKi#1
MEKi#2
ERKi#1
RAFi #1
RAFi #2
RAFi #4
RAFi #1
RAFi #2
RAFi #4
Data for RAFi #4
4x RAFi
2x MEKi
1x ERKi
{Source: Alain van Gool, unpubl. data 2008}
38 Alain van Gool, ECPM course, Basel, 1 Feb 2016
39. • ~200 genes with >10 fold change.
• Overlap and differences between compound-regulated genes
• Methods applied to select new candidate biomarkers for validation, e.g. as
secreted proteins in plasma
• Selection of ERK pathway responsive transcripts, e.g. IL-8
Selection biomarkers from pharmacogenomics A375 cells
RAFi#4
RAFi#1
RAFi#2
ERKi#1
RAFi#3
MEKi#1
MEKi#2
DMSO
{Source: Alain van Gool, unpubl. data 2008}
39 Alain van Gool, ECPM course, Basel, 1 Feb 2016
40. {Yurkovetsky, et al. Clin Cancer Res 2007;13(8) April 15, 2007}
123 pg/ml
9 pg/ml
p < 0.001
Determination of IL-8 levels (one of 29 serum cytokines analyzed) in
179 melanoma patients (stage II & III) & 379 healthy individuals
Literature: elevated levels of IL-8 in melanoma patients
40 Alain van Gool, ECPM course, Basel, 1 Feb 2016
41. Validation study to confirm IL-8 in melanoma
Tissue Matching plasma + serum
Normal Healthy Controls 40 50
Stage 1 11 11
Stage 2 11 11
Stage 3, non-metastatic 4 4
Stage 3, metastatic 11 11
Stage 4, non-metastatic 3 3
Stage 4, metastatic 19 19
Clinical samples used (from two independent commercial biobanks)
Stage 1 Stage 2 Stage 3 Stage 4
H&E staining; 20x
{Source: Alain van Gool, unpubl. data 2010}
41 Alain van Gool, ECPM course, Basel, 1 Feb 2016
42. Validation study to confirm IL-8 in melanoma
Stage 1 Stage 2 Stage 3 Stage 4
H&E staining; 20x
Analysis done:
• Genetic analysis for BRAFV600E/D mutation in genomic DNA from tissue samples
• IL-8 mRNA analysis in tissue samples by in situ hybridisation using bDNA probes
(multiplexing with 12 ERK pathway response transcripts)
• IL-8 protein analysis in tissue samples by immunohistochemistry (in parallel with 4 other
ERK pathway response proteins, Ki67, Tunnel)
• IL-8 protein analysis in matching plasma and serum by IL-8 immunoassay (3 formats:
ELISA, Luminex, Mesoscale; singleplex and multiplex)
• Statistical data analysis
{Source: Alain van Gool, unpubl. data 2010}
42 Alain van Gool, ECPM course, Basel, 1 Feb 2016
43. No change in plasma & serum IL-8 levels in melanoma
Serum IL-8 levels in various Stages of Melanoma
Healthy control (n=10) Melanoma (n=37)
0
20
40
60
80
MeanIL-8levels(pg/ml)
Plasma IL-8 levels in various Stages of Melanoma
Healthy control (n=20) Melanoma (n=59)
0
5
10
15
20
MeanIL-8levels(pg/ml)
No confirmation of literature: no change in IL-8 protein levels in melanoma.
Reason?
Analytics ok ! Literature correct? Sample ok?
{Source: Alain van Gool, unpubl. data 2010}
43 Alain van Gool, ECPM course, Basel, 1 Feb 2016
45. Build biomarker validation pipelines
Standardisation, harmonisation,
knowledge sharing in:
1. Assay development
2. Clinical validation
NL Roadmap Molecular Diagnostics (2012) NL Grant 4.3M Eur (2014)
45 Alain van Gool, ECPM course, Basel, 1 Feb 2016
(Netherlands)
46. Ongoing independent biomarker activities
46
Europe
USA
{Asadullah et al, Nature Reviews Drug Discovery, Dec 2015}
46 Alain van Gool, ECPM course, Basel, 1 Feb 2016
47. The Good Biomarker Practice initiative
Join forces among Europe’s major academic infrastructures + industry to:
1. Establish “Good Biomarker Practice” guidelines
- on translational research, biomarker technologies, biobanking, data stewardship.
2. Efficiently execute high quality biomarker projects
- work together in clinical validation and development of probable biomarkers.
47
47 Alain van Gool, ECPM course, Basel, 1 Feb 2016
48. Take home messages
• Biomarkers have become an integrate part of drug discovery and
development as key drivers of translational medicine and personalized
healthcare
• Planning and execution of Biomarker strategy and development should be
done consistently from early lead compound to clinical proof-of-concept.
• Novel technologies in laboratories and selfmonitoring yield promising
opportunities for new biomarkers and applications
• Mind the biomarker innovation gap!
• Ensure thorough preparation of biomarker discovery, validation and
development and include lessons-learned from others to increase chance of
success
48
48 Alain van Gool, ECPM course, Basel, 1 Feb 2016
49. Acknowledgements
Ron Wevers
Jolein Gloerich
Hans Wessels
Dirk Lefeber
Monique van Scherpenzeel
Leo Kluijtmans
Lucien Engelen
Nathalie Bovy
Paul Smits
Maroeska Rovers
Bas Bloem
and many others
www.radboudumc.nl/personalizedhealthcare
www.radboudumc.nl/research/technologycenters
www.radboudresearchfacilities.nl
alain.vangool@tno.nl
alain.vangool@radboudumc.nl
www.linkedIn.com
www.slideshare.net/alainvangool
Many collaborators and funders
Jan van der Greef
Ben van Ommen
Bas Kremer
Lars Verschuren
Ivana Bobeldijk
Marjan van Erk
Carina de Jongh
Peter van Dijken
Peter Wielinga
Robert Kleemann
Suzan Wopereis
and many others
CarTarDis
49 Alain van Gool, ECPM course, Basel, 1 Feb 2016