Biomarkers have a diversified role in diagnosis, prognostication and risk stratification. This presentation aims to compile the basic information and new literature on various biomarkers pertaining to cancer care.
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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What is biomarker?
What is the purpose of biomarker
Processes of biomarker development?
Types of Biomarkers
What is biomarker testing for cancer treatment?
Uses of Biomarkers in Cancer Medicine
Uses of Biomarkers in Cancer Drug Discovery
A wonderful slide for tumor markers in GI surgery. Cancer biomarkers are often used in monitoring response in cancer.
Tumor marker, biomarkers in common practice.
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
Follow our social media accounts:
Twitter - https://twitter.com/survivornetca
Facebook - https://www.facebook.com/CanadianSurvivorNet
Pinterest - https://www.pinterest.com/survivornetwork
YouTube - https://www.youtube.com/user/Survivornetca
What is biomarker?
What is the purpose of biomarker
Processes of biomarker development?
Types of Biomarkers
What is biomarker testing for cancer treatment?
Uses of Biomarkers in Cancer Medicine
Uses of Biomarkers in Cancer Drug Discovery
A wonderful slide for tumor markers in GI surgery. Cancer biomarkers are often used in monitoring response in cancer.
Tumor marker, biomarkers in common practice.
Liquid Biopsy Overview, Challenges and New Solutions: Liquid Biopsy Series Pa...QIAGEN
A liquid biopsy is often described as a sensitive and specific blood test to detect circulating tumor cells (CTCs). CTCs, shed by both the primary and metastasized tumors, carry specific information about their origins and markers that will enable us to discover new diagnosis, prognosis and therapeutic targets. This slidedeck gives an overview of the recent progress in exploring the predictive potential of circulating biomarkers, including circulating tumor cells, circulating tumor DNA, microRNAs, long non-coding RNAs (lncRNAs) and exosomes. Addressing both biological and technical aspects, we detail the isolation and characterization of circulating biomarkers. Challenges and solutions are also featured.
Introduction to Targeted Therapies in OncologyMohamed Abdulla
Describes the molecular background which represents the core for developing targeted therapies against specific biological events in malignant cellular clones.
How can immunotherapy be used to treat metastatic breast cancer? Ian Krop, MD, PhD, discusses the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 and hosted by the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
Breast cancer & biomarkers, their types, novelty of breast cancer biomarkers. Detailed study of her2, p53, BRCA1, BRCA2, DPD, 21-Gene signature, 70-Gene signature, cd106, vcam1, nlr, bFGF, mammaglobin, ER, PR, CEA. Pthological samples for biomarkers test, Ranges of various biomarkers, breast cancer diagnosis, prognosis, occurance, selection of breast caner treatment like targeted therapy.
Tumour Markers are substances present in the tumour, produced by the tumour or by the host as a response to the presence of the tumour, providing information about biological characteristics of the tumour. these tumour markers may specific for the tissue but often get elevated in neoplastic as well non-neoplastic lesions, further Various analytical platforms available for serum tumour markers lack standardisation. These factors add to interpretative challenges in serum tumour markers
This ppt will provide you a brief yet effective information about major types of biomarkers, their definitions, their significance in disease dignosis & treatment, how they are being & are developed to be used as an effective dignostic tool for Cancer & their other future implications in other fields of medicine.
Liquid Biopsy Overview, Challenges and New Solutions: Liquid Biopsy Series Pa...QIAGEN
A liquid biopsy is often described as a sensitive and specific blood test to detect circulating tumor cells (CTCs). CTCs, shed by both the primary and metastasized tumors, carry specific information about their origins and markers that will enable us to discover new diagnosis, prognosis and therapeutic targets. This slidedeck gives an overview of the recent progress in exploring the predictive potential of circulating biomarkers, including circulating tumor cells, circulating tumor DNA, microRNAs, long non-coding RNAs (lncRNAs) and exosomes. Addressing both biological and technical aspects, we detail the isolation and characterization of circulating biomarkers. Challenges and solutions are also featured.
Introduction to Targeted Therapies in OncologyMohamed Abdulla
Describes the molecular background which represents the core for developing targeted therapies against specific biological events in malignant cellular clones.
How can immunotherapy be used to treat metastatic breast cancer? Ian Krop, MD, PhD, discusses the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 and hosted by the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
Breast cancer & biomarkers, their types, novelty of breast cancer biomarkers. Detailed study of her2, p53, BRCA1, BRCA2, DPD, 21-Gene signature, 70-Gene signature, cd106, vcam1, nlr, bFGF, mammaglobin, ER, PR, CEA. Pthological samples for biomarkers test, Ranges of various biomarkers, breast cancer diagnosis, prognosis, occurance, selection of breast caner treatment like targeted therapy.
Tumour Markers are substances present in the tumour, produced by the tumour or by the host as a response to the presence of the tumour, providing information about biological characteristics of the tumour. these tumour markers may specific for the tissue but often get elevated in neoplastic as well non-neoplastic lesions, further Various analytical platforms available for serum tumour markers lack standardisation. These factors add to interpretative challenges in serum tumour markers
This ppt will provide you a brief yet effective information about major types of biomarkers, their definitions, their significance in disease dignosis & treatment, how they are being & are developed to be used as an effective dignostic tool for Cancer & their other future implications in other fields of medicine.
Tumor Biomarkers For Screening, Progression and Prognosis Vivek Misra
Tumor markers are substances that can be found in the body (usually in the blood or urine) when cancer is present. Along with other tests, tumor markers can be used to help show if cancer is present, to determine the type of cancer, and in some cases to help show if treatment is working. Some of the more common tumor markers are discussed here.
As of June 2014, Apple announced there were 1.2 million apps available to download in their iOS app store. In such a crowded and growing marketplace it’s hard for apps to stand out. Hundreds of thousands of apps remain buried in the depths of the App Store, unused, un-downloaded and unloved.
Everyone wants to be the next Uber, Instagram or Candy Crush.
So… what’s their secret to success?
Part of their secret is creating a great product that is integrated into the lives of its users.
But, what a lot of people forget is how difficult it can be to find & acquire loyal app users. We believe that’s the second half of the secret.
While there’s no specific formula for success, we’ve created a guide for successfully marketing your mobile app.
Based on our past experience and brand and mobile expertise we’ve put together a guide for marketing mobile apps. In this toolkit, we share 8 things that every mobile app processes, resources and recommendations that we’re confident will guide your app to success.
2014 11-27 ODDP 2014 course, Amsterdam, Alain van GoolAlain van Gool
Presentation as part of a comprehensive oncology drug development course, to discuss a pharmaceutical approach to identify, validate and develop biomarkers for personalized medicine for melanoma.
2015 11-26 ODDP2015 Course Oncology Drug Development, Amsterdam, Alain van GoolAlain van Gool
Tutorial lecture explaining real case stories of oncology drug development, passing on lessons learned from my pharma days to an audience of research professionals.
The Journal of Biomarkers in Drug Development (JBDD) promotes rigorous research that makes a significant contribution in advancing knowledge for Biomarkers in Drug Development. JBDD includes all major themes pertaining to Biomarkers used in Drug Development.
Tumor markers
Many cancers are associated with the abnormal production of some molecules which can be measured in plasma. These molecules are known as tumor markers.
A good tumor maker should have those properties:
1. A tumor marker should be present in or produced by tumor itself.
2. A tumor marker should not be present in healthy tissues.
3. Plasma level of a tumor marker should be at a minimum level in healthy subjects and in benign conditions.
4. A tumor marker should be specific for a tissue, it should have different immunological properties when it is synthesized in other tissues.
5. Plasma level of the tumor marker should be in proportion to the both size of the tumor and the activity of the tumor.
6. Half-life of a tumor should not be very long
7. A tumor marker should be present in plasma at a detectable level, even though tumor size is very small
In the recent years, knowledge about cancer biomarkers has increased tremendously
providing great opportunities for improving the management of cancer patients by
enhancing the efficiency of detection and efficacy of treatment.
• Recent technological advancement has enabled the examination of many
potential biomarkers and renewed interest in developing new biomarkers.
• Biomarkers of cancer could include a broad range of biochemical entities, such as nucleic
acids, proteins, sugars, lipids, and small metabolites, cytogenetic and cytokinetic
parameters as well as whole tumour cells found in the body
fluid. A COMPREHENSIVE UNDERSTANDING OF THE RELEVANCE
OF EACH BIOMARKER WILL BE VERY IMPORTANT NOT
ONLY FOR DIAGNOSING THE DISEASE RELIABLY, BUT ALSO
HELP IN THE CHOICE OF MULTIPLE THERAPEUTIC
ALTERNATIVES CURRENTLY AVAILABLE THAT IS LIKELY TO
BENEFIT THE PATIENTS.• Measure or evaluate the normal biological process, pathogenic processes, or
pharmacological response to a therapeutic interventions.
• Includes ~ diagnostic test and imaging technology
• “ Cancer is clusters disease involving alterations in status and expression of
multiple genes that confer a survival advantage & diminished proliferative
potential to somatic or germinal cells"
Specific to tumor
• Level change in response to tumor size
• No fluctuations in level
• Low level in healthy individual
• Predict recurrence
• Test should be cost effective
DNA methylation
2. Alteration pattern of histone modification
3. Alterations in chromatin condensation
The presentation aims to be of introductory level. Classification of tumor markers along with brief description of selected tumor markers are provided.Applications and methods are listed but not discussed at length.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
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ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
2. Definition
• “A biological molecule found in blood, other body fluids, or tissues
that is a sign of a normal or abnormal process, or of a condition or
disease
• Tumor markers: types of biomarkers that can be found in the body
when cancer is present
• Require special assay that is beyond routine clinical, radiographic,
or pathologic examination
“Biomarker"NCI Dictionary of Cancer Terms. National Cancer Institute
4. 4
In colon cancer KRAS mutation determines response
to EGFR therapy
Mutant KRAS
+EGFR
-EGFR
Wild type KRAS
+EGFR
-EGFR
Amado et al. J Clin Oncol; 26:1626-1634 2008
KRAS mut PIK3CA mut
BRAF mut
5. Types
Prognostic
biomarker
Predictive
biomarker
Disease
related
Drug related
Course of disease irrespective
of treatment used e.g
-Presence of involved local-
regional lymph nodes
Response to a particular treatment e.g.
-KRAS mutations and antiepidermal growth factor
receptor [EGFR] antibody therapies
Many are mixed biomarkers i.e. carry both prognostic and predictive value e.g HER2 neu:
• Amplification or overexpression of HER2 is associated with worse prognosis in
absence of therapy
• HER2 favorable predictive factor for some types of therapy, e.g anthracycline or
taxane-based chemotherapy, and anti-HER2 therapies (trastuzumab and lapatinib)
In NSCLC
• High expression of excision repair cross-complementation gene-1 (ERCC1) associated
with decreased response to platinum-based chemotherapy, but with better overall
prognosis
• Ribonucleotide reductase M1 (RRM1) overexpression correlates with better de
novo prognosis but resistance to gemcitabine
Olaussen KA et al. N Engl J Med 2006;355:983
6. Specimen
• Measured at multiple levels:
– DNA
• Gene mutations, deletions, amplifications, or methylation
– RNA
• Micro RNA,mRNA
– Protein
• Overexpression, under expression, or qualitative abnormalities
– Cells or Tissue
• Presence of cells outside their milieu e.g in circulation
• Demonstration of neovascularization in tissue specimen
7. Clinical Usefulness
• Risk determination
– Adjust risk categorization for individual not affected by disease
– E.g. BRCA 1 & 2 mutation analysis
• Screening
– Prostate specific antigen for carcinoma prostate
• Differential diagnosis
– Analysis of circulating α-fetoprotein (AFP) or β–human chorionic
gonadotropin (β-hCG) in males with poorly differentiated malignancies
of uncertain origin
• Prognosis
– Presence of involved local-regional lymph nodes associated with
subsequent distant recurrence
• Prediction
– Estrogen-receptor content for endocrine therapy
• Monitoring
8. Some General Points About Tumor Biomarkers
• No serum marker in current use is specific for malignancy
• Generally, serum marker levels are rarely elevated in patients with
early malignancy
– With a few exceptions, high levels are usually found only when
patients have advanced disease.
• No cancer marker has absolute organ specificity
– PSA relatively specific for prostate tissue, but not for prostate
cancer
9. General Points…..
• No marker is elevated in 100% of patients with particular malignancy
– Exception: hCG in choriocarcinoma
• Requesting of multiple markers (such as CEA and the CA series of antigens)
in an attempt to identify metastases of unknown primary origin is rarely of use
• Tumour markers assays should not be carried out on biological fluids e.g
(peritoneal fluids, pancreatic juice and ovarian cystic fluids) as reliable
reference ranges currently unavailable
10. General Points…
• Reference ranges for cancer markers are not well defined and are used only
for guidance
• Level below the reference range does not exclude malignancy while
concentrations above the reference range does not necessary mean the
presence of cancer
• Changes in levels over time are likely to be more clinically useful than
absolute levels at one point in time
• As many tumour markers lack agreed International Reference Preparations
(e.g CA125, CA15-3, CA19-9), different assay kits may give different
results for the same sera
• Laboratories carrying out tumour marker tests should state the assay used
on their report form
11. Ideal Tumor Markers
• Be specific to the tumor
• Level should change in response to tumor size
• Abnormal level should be obtained in presence of micrometastases
• Level should not have large fluctuations that are independent of changes in
tumor size
• Levels in healthy individuals are at much lower concentrations than those
found in cancer patients
• Predict recurrences before they are clinically detectable
• Test should be cost effective
13. Alpha Feto Protein
• 70 kDa glycoprotein homologous to albumin
• Forms in serum:
– Exhibits micro heterogeneity due to varying levels of
glycosylation
– AFP produced by malignancies more highly fucosylated than
formed by normal tissues
– Existing assay do not differentiate between various forms
• Half life: 5-7 days
14. Alfa Feto Protein
• Mainly confined to 3 malignancies, i.e.
a. Germ cell tumours (NSGCT) of testis, ovary and other sites
b. Hepatocellular carcinoma (HCC)
c. Hepatoblastoma (in children, extremely rare in adults)
• Benign conditions
– Hepatitis
– Cirrhosis
– Biliary tract obstruction
– Alcoholic liver disease
– Ataxia telangiectasia
– Hereditary tyrosinaemia
Physiological conditions
with elevated levels:
• Pregnancy
• 1st year of life
15. AFP: Clinical Applications
• In combination with hCG, for monitoring patients with NSGCT
• Independent prognostic marker for NSGCT (e.g. of the testis)
• Diagnostic aid for HCC and hepatoblastoma.
– In patients with cirrhosis and a focal lesion > 2 cm with arterial
hypervascularization, an AFP level >200 µg/L is suggestive of HCC,
and AFP>400 µg/L is strongly suggestive of HCC
• Screening for HCC in high risk populations (e.g. in patients with cirrhosis
due to hepatitis B or C)
– 6-monthly AFP measurement and abdominal ultrasound, with AFP>200
µg/L and rising
Not a useful marker for liver metastases
16. CA125
• Protein detected by this antibody is Muc16
• Physiological function: None established
• Malignancies with elevated levels:
– Epithelial ovarian cancer; 80 - 85% of all cases; but increased in only
half of early (stage 1) cancer
– May be elevated in any adenocarcinoma with advanced disease
• Benign conditions with elevated levels:
– Endometriosis
– Acute pancreatitis
– Cirrhosis
– Peritonitis
– Inflammatory pelvic disease
– Presence of ascites (of non-malignant origin)
Physiological conditions with elevated
levels:
• Menstruation & pregnancy (usually
< 100 kU/L)
17. CA-125
• Reference range: 0 - 35 kU/L (most frequently used range)
• Half life : Approx. 5-7 days
• Clinical application:
– Measurement in postmenopausal patients with pelvic masses may help
differentiate malignant from benign lesions
– Rate of decline during initial therapy is an independent prognostic
indicator in ovarian carcinoma
– Monitoring treatment with chemotherapy
– Surveillance following initial treatment
• Unclear impact on survival
18. CA 19-9
• Mucin reacting with monoclonal antibody 111 6 NS 19-9
• Physiological function: Involved in cell adhesion
• Reference range : Very variable, from 0 - 37 kU/L to 0 - 100 kU/L
• Half life in serum: Approx. 1 day (can vary from <1 day to 3 days)
19. CA-19-9
• Malignancies with elevated levels
– Most pancreatic adenocarcinomas
– Approx. 50% of gastric carcinomas
– approx. 30% of colorectal carcinomas.
• Benign conditions with elevated levels
– Acute and chronic pancreatitis
– Hepatocellular jaundice ;Cirrhosis
– Acute cholangitis
• Main clinical applications
– As diagnostic aid for pancreatic carcinoma
• Inadequate sensitivity & specificity limit the use in early diagnosis
– Monitoring treatment of patients with pancreatic adenocarcinoma
– Diagnostic aid in gastric and cholangio carcinomas
20. CA 15-3
• Transmembrane glycoprotein encoded by MUC1 gene
– Defined by reactivity with 2 monoclonal antibodies, i.e., DF3
and 115D8 in sandwich immunoassay
• Physiological function: Involved in cell adhesion & cancer
pathogenesis
• Reference range :0 – 25 to 0 – 40 kU/L
• Half life in serum :Unknown
21. CA15-3
• Malignancies with elevated levels :
– Breast adenocarcinomas, especially with distant metastasis
• Rarely elevated in patients with local breast cancer
• Benign diseases with elevated levels
– Benign liver disease
– Benign breast disease (possibly)
• Main clinical applications:
– Preclinically detecting recurrences in asymptomatic patients with
diagnosed breast cancer
• Controversial
– For monitoring the treatment of patients with advanced breast
cancer
22. CEA
• 200 kDa (approx.) glycoprotein
• Physiological function: Role in cell adhesion & inhibition of
apoptosis
• Reference range: 0 - 3.5 µg/L to 0 - 5.0 µg/L.
• Half life in serum :Approx. 3 days but can vary from 1 to 5 days
23. CEA
• Malignancies with elevated levels
– Elevated in almost any advanced adenocarcinoma, i.e., where distant
metastases present
• Almost never elevated in early malignancy
• Benign diseases with elevated levels:
– Involving liver :Hepatitis, cirrhosis, alcoholic liver disease
– Obstructive jaundice
– Ulcerative colitis, Crohn’s disease
– Pancreatitis
– Bronchitis, emphysema
– Mildly elevated in smokers
• Main clinical applications
– In surveillance following curative resection of colorectal cancer
– In monitoring therapy in advanced colorectal cance
24. Human Chorionic Gonadotropin (hCG)
• Heterodimer composed of 2 glycosolated sub-units (alpha & beta chains)
– Alpha chain is almost identical to alpha chain in TSH, FSH & LH
– Beta chain is distinct from corresponding chains
• Distinctive 24 amino acid carboxy-terminal extension
• Forms in serum: Multiple forms
– Intact 2-chain peptide
– Free alpha and beta chains
– Various degradation products (e.g., beta core fragment)
• Physiological function: to maintain progesterone production by corpus
luteum during early pregnancy
– Can be detected as early as one week after conception
25. hCG
• Malignancies with elevated levels
– Virtually all patients with gestational trophoblastic disease (GTD)
(i.e., complete and partial molar pregnancy, choriocarcinoma and placental
site trophoblastic tumours)
– Non-seminomatous germ cell tumours (NSGCT)
– Seminomatous germ cell tumours of testis (approx. 20%).
• Benign Diseases with elevated levels
– Ectopic pregnancy
– Pituitary adenoma
• Main clinical applications
– For monitoring patients with GTD
– In conjunction with AFP, for determining prognosis and monitoring
patients with NSGCT of testis, ovary and other sites
26. hCG
• Type of sample for assay
– Serum or urine
• Reference range : Serum: 0 - 5 IU/L
• Half life in serum: Approx. 16 - 24 hours; decline may be biphasic
with a second half life of 13 days
27. Prostate Specific Antigen (PSA)
• 28.4 kDa single chain chymotrypsin-like serine protease containing 237
amino acids
• Forms in serum
– PSA complexed with
• A1antichymotrypsin (PSA-ACT) (major)
• A1 -antitrypsin (trace quantity)
• A2 -macroglobulin (undetectable by current immunoassays)
• Non-complexed free form (fPSA) represents 5 - 40% of the “total”
PSA
• Physiological function
– Partially responsible for the liquefaction of semen to promote the
release and motility of spermatozoa
28. PSA…..
• 5-alpha-reductase inhibitors used to treat BPH reduce PSA levels by approx.
50%
• Half life in serum: Approximately 2.5 days after radical prostatectomy; after
radiotherapy may be many months
• Reference range: 0 - 4 µg/L (most frequently used)
Effects of urological manipulations on PSA levels
• DRE: May cause minor increases ; rarely of clinical significance.
• Prostate massage: May cause minor elevations
• TURP: Increases PSA levels significantly. Wait >/=6 weeks before testing
• Needle Biopsy: Increases PSA levels significantly. Wait >/=6 weeks before testing
• Cystoscopy: No change by flexible cystoscopy but rigid cystoscopy may increase levels
29. Prostate Specific Antigen (PSA)
• Main clinical applications
– In combination with digital rectal examination PSA can aid diagnosis
of prostate cancer
– Determining prognosis in patients with prostate cancer
– Surveillance following diagnosis of prostate cancer
– Monitoring therapy in patients with diagnosed prostate cancer
– As screening tool : Controversial
– No significant reduction in mortality from prostate cancer1
– 20% reduction in mortality but at expense of overdiagnosis2
1)Andriole GL.N Engl J Med 2009;360:1310-1319.
2)Schröder FH.N Engl J Med 2009;360:1320-1328
• PSA Density - Normalized to prostate volume
• PSA Velocity - Change in PSA over time (e.g., more than 15% per year)
• Free PSA/Total PSA - lower ratio suggests cancer, since more free PSA from
normal prostate is degraded (< 10% - biopsy)
30.
31. Cancer Marker
Breast Tissue ER, PgR (some uterine and lung cancers are
weakly positive)
Gross cystic disease protein
Colon/intestine Tissue CDX2
Lung Tissue TTF1 (also positive in thyroid cancer, but
thyroid also positive for thyroglobulin)
Melanoma Tissue S100, Melan-A, HMB45, MITF
Ovarian WT1
Prostate Circulating or tissue PSA, urinary PCA3
Male germ cell Tissue or circulating α-fetoprotein, β–human chorionic
gonadotropin (β-hCG)
Tissue PLAP
Accepted Biomarkers Useful for Differential
Diagnosis of Common Solid Malignancies
32. Accepted Biomarkers Useful as Predictive Factors
for Treatment in Common Solid Malignancies
Cancer Marker Treatment
Breast ER Endocrine
HER2 Trastuzumab; lapatinib
Colon KRAS mutations Cetuximab; panitumumab
Lung EGFR mutations
ALK positive
Tyrosine kinase inhibitors
(erlotinib, gefitinib)
Crizotinib
33. Accepted Biomarkers Useful for Monitoring
of Common Solid Malignancies
Cancer Marker Specific Situation
Breast CA 15-3, CA 27.29
Circulating Tumor Cells
Monitor selected patients with metastatic disease
Colon CEA Monitor patients after primary and systemic adjuvant
chemotherapy to detect resectable relapse
Monitor selected patients with metastatic disease
Lung None
Melanoma None
Ovarian CA 125 Monitor patients after primary and adjuvant chemotherapy
for relapse
Monitor patients with metastatic disease
HE-4 Monitor patients with metastatic disease who are CA
125 negative
Prostate PSA Monitor patients after primary and adjuvant chemotherapy
for relapse
Monitor patients with metastatic disease
Male germ line
malignancy
β-hCG; AFP Monitor patients after primary and adjuvant chemotherapy
for relapse
Monitor patients with metastatic disease
Female
choriocarcinoma
β-hCG Monitor patients after primary and adjuvant chemotherapy
for relapse
Monitor patients with metastatic disease
34. Guidelines For Ordering/
Interpreting Tumor Marker Tests
• Never rely on result of single test
• Order every test from the same laboratory
• Consider half-life of the tumor when interpreting result
• Consider how the Tumor Marker is removed or metabolized
36. OVA1
• First FDA-cleared protein-based in vitro diagnostic multivariate index assay
• Test 5 proteins in blood sample
– β2-microglobulin, transferrin, apolipoprotein A1, transthyretin
– CA125
• Indicate the likelihood of benign or malignant
• OVA1 identified additional patients with potential malignancies
• Help to guide surgical decisions in patients with pelvic masses
Giede KC et al. Gynecol oncol. 205;99:447-461
38. Conclusions
Five-gene signature is closely associated with relapse-free and overall survival
among patients with NSCLC.
Dual-specificity phosphatase 6 (DUSP6),
monocyte-to-macrophage differentiation associated protein (MMD),
signal transducer and activator of transcription 1 (STAT1),
v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3 (ERBB3), lymphocyte-
specific protein tyrosine kinase (LCK).
39. Oncotype Dx
• Quantifies the likelihood of disease recurrence in women with early-stage
hormone ER positive only breast cancer
• Development of a high-throughput, real time, RT-PCR method to quantify
gene expression from fixed tumor tissue samples
• Selection of 250 candidate genes
• Testing the relationship between the 250 candidate genes and risk of
recurrence in a series of 447 pts from three clinical studies
Published literature
Genomic databases
DNA array-based experiments
16 cancer-related genes + 5 reference genes → Oncotype DX (recurrence score)
Paik et al. NEJM. 2004.
40. RS = + 0.47 x HER2 Group Score
- 0.34 x ER Group Score
+ 1.04 x Proliferation Group Score
+ 0.10 x Invasion Group Score
+ 0.05 x CD68
- 0.08 x GSTM1
- 0.07 x BAG1
PROLIFERATION
Ki-67
STK15
Survivin
Cyclin B1
MYBL2
ESTROGEN
ER
PR
Bcl2
SCUBE2
INVASION
Stromelysin 3
Cathepsin L2
HER2
GRB7
HER2
BAG1 GSTM1
REFERENCE
Beta-actin
GAPDH
RPLPO
GUS
TFRC
CD68
Paik et al. N Engl J Med. 2004;351:2817-26.
16 cancer genes and 5 reference genes make up the Oncotype DX
gene panel. The expression of these genes is used to calculate the
recurrence score:
Oncotype DX 21-gene recurrence score
42. Oncotype DXTM
– Low RS associated with minimal chemotherapy benefit
– High RS associated with large chemotherapy benefit
– The Oncotype DX Recurrence Score provides precise,
quantitative information for individual patients on prognosis
across and statistically independent of information on patient age,
tumor size, and tumor grade.
44. MicroRNA Profile in Diagnosis and Prognosis
• miRNAs are small non-coding RNAs which play
key roles in regulating translation & degradation of
mRNAs
• Genetic and epigenetic alteration may affect
miRNA expression, thereby leading to aberrant
target gene(s) expression in cancers
Yanaihara et al, Cancer Cell, 2006:
- miRNA profiles of 104 pairs of primary
lung cancers and corresponding non-
cancerous lung tissues were analyzed by
miRNA microarrays
- High hsa-mir-155 a expression correlated with
poor survival
Yanaihara et al .Cancer Cell. 2006 Mar;9(3):189-98
45. The role of microRNAs in cancer diagnosis
• With the application of in situ RT-PCR, it was shown that the
aberrantly expressed miR-221, miR-301 and miR-376a were
localized to pancreatic cancer cells but not to stroma or normal
acini or ducts.
• Aberrant miRNA expression offered new clues to pancreatic
tumorigenesis and might provide diagnostic biomarkers for
pancreatic cancer.
Lee EJ, et al. Expression profiling identifies microRNA signature in pancreatic cancer.
Int J Cancer 2007, 120:1046-1054.
Cho WC. MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy.
Int J Biochem Cell Biol 2010.
Cho WC. MicroRNAs in cancer - from research to therapy. Biochim Biophys Acta - Rev Cancer
2010;1805(2):209-217.
46. The role of microRNAs in cancer prognosis
• The expression pattern of miRNAs in pancreatic cancer were
compared with those of normal pancreas and chronic
pancreatitis using miRNA microarrays.
• Differentially expressed miRNAs were identified which could
differentiate pancreatic cancer from normal pancreas, chronic
pancreatitis, or both.
• High expression of miR-196a-2 was found to predict poor
survival of more than 24 months.
Bloomston M, et al. MicroRNA expression patterns to differentiate pancreatic
adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA 2007,
297:1901-1908.
47. The role of microRNAs in cancer prognosis
• Expression of let-7 miRNA was frequently reduced in
human lung cancers, and that reduced let-7 miRNA
expression was significantly associated with shorter
postoperative survival.
• Overexpression of let-7 miRNA in A549 lung
adenocarcinoma cell line inhibited lung cancer cell
growth in vitro.
Takamizawa J, et al. Reduced expression of the let-7 microRNAs in human
lung cancers in association with shortened postoperative survival. Cancer Res
2004, 64:3753-3756.
48. microRNAs Tumorigenesis Diagnosis Prognosis
miR-9 Neuroblastoma
miR-10b Breast cancer
miR-15, miR-15a Leukemia, pituitary adenoma
miR-16, miR-16-1 Leukemia, pituitary adenoma
miR-17-5p, miR-17-92 Lung cancer, lymphoma
miR-20a Lymphoma, lung cancer
miR-21 Breast cancer, cholangiocarcinoma, head & neck
cancer, leukemia
Pancreatic
cancer
miR-29, miR-29b Leukemia, cholangiocarcinoma
miR-31 Colorectal cancer
miR-34a Pancreatic cancer Neuroblastoma
miR-96 Colorectal cancer
miR-98 Head & neck cancer
miR-103 Pancreatic cancer
miR-107 Leukemia, pancreatic cancer
miR-125a, miR-125b Neuroblastoma, breast cancer
miR-128 Glioblastoma
miR-133b Colorectal cancer
miR-135b Colorectal cancer
miR-143 Colon cancer
miR-145 Breast cancer, colorectal cancer
miR-146 Thyroid carcinoma
49. Markers of Pharmacogenomics
• Difference due to :
– Inherited, germ-line differences in genes either responsible for
• Metabolism of drugs
• Target of drugs
– Play important role in assessing benefits & risks for specific
therapeutic strategies
50. Some Examples
Drug Enzyme /genes Effect
5 fluorouracil/capecitabine dihydropyrimidine
dehydrogenase (DPD)
Increased side-effects if
defective enzymes
6-mercaptopurine, 6-
thioguanine, azathioprine
Thiopurine
methyletransferase (TPMT)
Increased side-effects if
defective enzymes
Tamoxifen CYP2D6 Lack of efficacy
Irinotecan UGT1A1 Increased side-effects if
defective enzymes
Gemcitabine, Ara-C NT5C3, FKBP5 (genes) Increased expression
associated with better
response
Li et.al. Cancer Research 2008; 68: (17). Sept. 1, 2008
51. Prognosis
Cell Search
• To detect circulating tumor cells (CTC) in blood
– Nucleated cells ≥ 4 µm in diameter
• Captured from bloodstream using antibodies against EpCAM (epithelial cell
adhesion molecule)
• Before start of chemotherapy for CRPC, detection of ≥ 5 CTCs associated
with inferior OS
• Drop in CTCs to <5 on chemotherapy associated with improvement in OS
• Limitation: lack of detection of CTCs in many men with progressive,
metastatic CRPC
De Bono JS,et al. Clin Cancer Res October 1, 2008:14; 6302
53. Conclusion
• Marked development in the field of cancer biomarker
• Incorporation of technologies eg. Proteomics, genomics and
metabolomics to search and validate newer biomarkers
• However , a tumor marker which reliably separates normal from
abnormal and can be detected even in early stages is still missing
• Pharmacogenomics: potential tool for individualized therapy
55. Roche Chip for Cytochrome P450
Genes: CYPC19 and CYP2D6
Xie and Frueh, , Personalized Medicine 2005, 2, 325-337
• Comprehensive detection of gene variations
• Genotyping of two Cytochrome P450 genes
& provides predictive phenotype of
associated enzymatic activities, using DNA
purified from human blood
• Assay distinguishes 29 known
polymorphisms in CYP2D6 gene, including
gene duplication & gene deletion, & two
major polymorphisms in CYP2C19 gene
• Aids in treatment choice & individualizing
treatment dose