This document discusses the need for targeted cancer therapeutics to be tested in patient populations matched to the drug's mechanism of action. It notes that evaluating the HER2-targeted drug trastuzumab in all breast cancer patients, rather than just HER2-positive patients, would not have shown its benefits. The document also describes an emerging need for biobanks that provide well-annotated specimens and molecular analysis capabilities to support biomarker validation.
This document discusses the need for targeted cancer therapeutics and companion diagnostics. It summarizes TriStar's capabilities in providing access to annotated clinical samples and molecular analysis platforms to support biomarker validation. Key capabilities include access to over 2.5 million archived tumor samples and clinical data, as well as analytical services like IHC, FISH, and gene expression analysis. TriStar uses tissue microarrays to study tumor heterogeneity and biomarker prognostic relevance at a large scale.
Chemotherapy for Advanced
Peritoneal Mesothelioma presented by Robert N. Taub, MD, PhD of Columbia University at the Mesothelioma Applied Research Foundation conference in New York, NY on September 28, 2012. www.curemeso.org
The document discusses how tumor cells differ from normal cells in their dependence on extracellular matrix attachment for survival and proliferation. It describes how tumor cells can survive and grow independently of attachment to matrix, while detachment of normal cells from matrix leads to apoptosis. Several models are presented for studying the anchorage independence of tumor cells, including culturing normal mammary epithelial cells in suspension or embedded in 3D basement membrane cultures, and comparing their signaling and survival pathways under these different conditions.
1) Positron emission tomography (PET), especially using radiotracers like methionine (MET) and fluoroethyltyrosine (FET), has higher sensitivity and specificity than MRI for differentiating tumor recurrence from radiation necrosis in high-grade gliomas. MET-PET and FET-PET can detect larger tumor volumes than contrast-enhanced MRI.
2) Studies have found MET-PET and FET-PET to have near 100% sensitivity and 70-100% specificity for diagnosing recurrence, while MRI sensitivity is lower at 60-93.5% with low specificity of 22-50%.
3) PET may allow for more accurate surgical resection margins compared to MRI and avoid unnecessary re-
Current Chemotherapy and the
Future of Targeted Therapies presented by Lee Krug, MD, of Memorial Sloan-Kettering Cancer Center at the Mesothelioma Applied Research Foundation's conference in New York, NY on September 28, 2012. www.curemeso.org
A 49-year-old female presented with a recurrent brain lesion on MRI after initial radiotherapy for a hypothalamus tumor. 18F-FDG PET and SPECT with 201Tl, 99mTc-MIBI, and 99mTc-ECD showed increased uptake, suggesting the lesion was a tumor recurrence rather than radiation necrosis. A second course of radiotherapy was given. Follow-up found the right frontal lesion had progressed while a new left temporal lesion was detected, both indicative of recurrence based on imaging characteristics.
This document discusses expanding the use of radiation therapy for malignant pleural mesothelioma. It summarizes the current approaches and outcomes for three scenarios: post-pneumonectomy radiation, post-pleurectomy radiation, and radiation for unresectable disease. For each scenario, intensity modulated radiation therapy (IMRT) to the pleura is presented as a way to improve local tumor control and survival rates compared to conventional radiation techniques, though there are risks of fatal pneumonitis that require careful patient selection and planning. Overall the document evaluates the potential benefits of pleural IMRT across different disease stages while also acknowledging toxicity challenges.
Exploring the neuroblastoma epigenome: perspectives for improved prognosisMaté Ongenaert
EXPLORING THE NEUROBLASTOMA EPIGENOME: PERSPECTIVES FOR THE DISCOVERY OF PROGNOSISTIC BIOMARKERS
M. Ongenaert, A. Decock, J. Vandesompele, F. Speleman
Center for Medical Genetics, Ghent University, Ghent, Belgium (mate.ongenaert@ugent.be)
Neuroblastoma (NB) is a childhood tumor originating from sympathetic nervous system cells. Although recently new insights into genes involved in NB have emerged, the molecular basis of neuroblastoma development and progression still remains poorly understood. The best-characterized genetic alterations include amplification of the proto-oncogene MYCN, ALK activating mutations or amplification, gain of chromosome arm 17q and losses of 1p, 3p, and 11q. Epigenetic alterations have been described as well: caspase-8 (CASP8) and RAS-association domain family 1 isoform A (RASSF1A) DNA-methylation are important events for the development and progression of neuroblastoma. In total, there are about 75 genes described as epigenetically affected in NB cell lines and/or NB primary samples.
Most of these methylation markers are found using ‘candidate gene’ approaches and the methylation frequencies are usually very low. In order to find novel methylation markers that can be used for improved prognosis, we applied a whole-genome methylation screen. This technique relies on capturing with the MBD2 protein, containing a methyl-binding domain (MBD), with a very high affinity towards methylated genomic regions. In an initial phase, MBD2-seq was performed on 8 NB cell lines (where we also had micro-array data of, before and after treatment with DAC). As these results are promising, we will explore the complete methylomes of 45 primary NB tumors.
Based on an integrative analysis (re-expression results, expression micro-arrays, MBD2-sequencing on cell lines), 48 MSP (Methylation Specific PCR) assays were tested on 89 primary neuroblastoma patients of different risk categories. The results of this validation study demonstrate the power of epigenetic biomarkers as several assays are informative for prognosis and survival.
This document discusses the need for targeted cancer therapeutics and companion diagnostics. It summarizes TriStar's capabilities in providing access to annotated clinical samples and molecular analysis platforms to support biomarker validation. Key capabilities include access to over 2.5 million archived tumor samples and clinical data, as well as analytical services like IHC, FISH, and gene expression analysis. TriStar uses tissue microarrays to study tumor heterogeneity and biomarker prognostic relevance at a large scale.
Chemotherapy for Advanced
Peritoneal Mesothelioma presented by Robert N. Taub, MD, PhD of Columbia University at the Mesothelioma Applied Research Foundation conference in New York, NY on September 28, 2012. www.curemeso.org
The document discusses how tumor cells differ from normal cells in their dependence on extracellular matrix attachment for survival and proliferation. It describes how tumor cells can survive and grow independently of attachment to matrix, while detachment of normal cells from matrix leads to apoptosis. Several models are presented for studying the anchorage independence of tumor cells, including culturing normal mammary epithelial cells in suspension or embedded in 3D basement membrane cultures, and comparing their signaling and survival pathways under these different conditions.
1) Positron emission tomography (PET), especially using radiotracers like methionine (MET) and fluoroethyltyrosine (FET), has higher sensitivity and specificity than MRI for differentiating tumor recurrence from radiation necrosis in high-grade gliomas. MET-PET and FET-PET can detect larger tumor volumes than contrast-enhanced MRI.
2) Studies have found MET-PET and FET-PET to have near 100% sensitivity and 70-100% specificity for diagnosing recurrence, while MRI sensitivity is lower at 60-93.5% with low specificity of 22-50%.
3) PET may allow for more accurate surgical resection margins compared to MRI and avoid unnecessary re-
Current Chemotherapy and the
Future of Targeted Therapies presented by Lee Krug, MD, of Memorial Sloan-Kettering Cancer Center at the Mesothelioma Applied Research Foundation's conference in New York, NY on September 28, 2012. www.curemeso.org
A 49-year-old female presented with a recurrent brain lesion on MRI after initial radiotherapy for a hypothalamus tumor. 18F-FDG PET and SPECT with 201Tl, 99mTc-MIBI, and 99mTc-ECD showed increased uptake, suggesting the lesion was a tumor recurrence rather than radiation necrosis. A second course of radiotherapy was given. Follow-up found the right frontal lesion had progressed while a new left temporal lesion was detected, both indicative of recurrence based on imaging characteristics.
This document discusses expanding the use of radiation therapy for malignant pleural mesothelioma. It summarizes the current approaches and outcomes for three scenarios: post-pneumonectomy radiation, post-pleurectomy radiation, and radiation for unresectable disease. For each scenario, intensity modulated radiation therapy (IMRT) to the pleura is presented as a way to improve local tumor control and survival rates compared to conventional radiation techniques, though there are risks of fatal pneumonitis that require careful patient selection and planning. Overall the document evaluates the potential benefits of pleural IMRT across different disease stages while also acknowledging toxicity challenges.
Exploring the neuroblastoma epigenome: perspectives for improved prognosisMaté Ongenaert
EXPLORING THE NEUROBLASTOMA EPIGENOME: PERSPECTIVES FOR THE DISCOVERY OF PROGNOSISTIC BIOMARKERS
M. Ongenaert, A. Decock, J. Vandesompele, F. Speleman
Center for Medical Genetics, Ghent University, Ghent, Belgium (mate.ongenaert@ugent.be)
Neuroblastoma (NB) is a childhood tumor originating from sympathetic nervous system cells. Although recently new insights into genes involved in NB have emerged, the molecular basis of neuroblastoma development and progression still remains poorly understood. The best-characterized genetic alterations include amplification of the proto-oncogene MYCN, ALK activating mutations or amplification, gain of chromosome arm 17q and losses of 1p, 3p, and 11q. Epigenetic alterations have been described as well: caspase-8 (CASP8) and RAS-association domain family 1 isoform A (RASSF1A) DNA-methylation are important events for the development and progression of neuroblastoma. In total, there are about 75 genes described as epigenetically affected in NB cell lines and/or NB primary samples.
Most of these methylation markers are found using ‘candidate gene’ approaches and the methylation frequencies are usually very low. In order to find novel methylation markers that can be used for improved prognosis, we applied a whole-genome methylation screen. This technique relies on capturing with the MBD2 protein, containing a methyl-binding domain (MBD), with a very high affinity towards methylated genomic regions. In an initial phase, MBD2-seq was performed on 8 NB cell lines (where we also had micro-array data of, before and after treatment with DAC). As these results are promising, we will explore the complete methylomes of 45 primary NB tumors.
Based on an integrative analysis (re-expression results, expression micro-arrays, MBD2-sequencing on cell lines), 48 MSP (Methylation Specific PCR) assays were tested on 89 primary neuroblastoma patients of different risk categories. The results of this validation study demonstrate the power of epigenetic biomarkers as several assays are informative for prognosis and survival.
The document discusses MAGE genes, which code for tumor antigens recognized by cytotoxic T lymphocytes. It provides background on MAGE genes, including that they were first identified in melanoma in 1991. MAGE genes are expressed in various cancers but not most normal tissues. The expression of certain MAGE genes has been associated with prognosis in cancers like lung and prostate cancer. Immunotherapies targeting MAGE antigens show potential for cancer treatment by activating CD8+ T cells against tumor cells. However, the tumor microenvironment can also induce immune suppression, presenting a barrier to the clinical efficacy of cancer vaccines.
This document discusses genomic signatures that can predict the risk of metastasis in breast cancer. Specifically, it summarizes that the 70-gene MammaPrint profile and intrinsic subtypes can predict metastasis risk and guide adjuvant therapy. Additionally, these genomic profiles are often maintained throughout the metastatic process, from the primary tumor to distant metastases in various sites. However, while profiles predict metastasis risk, they cannot predict the specific site of metastasis. Intrinsic subtypes show non-random associations with certain metastasis sites.
The incidence of malignant pleural mesothelioma in Europe will peak between 2015-2020. Key molecular alterations involve inactivation of tumor suppressors p16 INK4A/p14ARF and NF2. Pemetrexed plus cisplatin is standard first-line chemotherapy. Vinorelbine may be used second-line. Selected patients benefit from multimodality therapy including neoadjuvant chemotherapy, extrapleural pneumonectomy, and potentially radiotherapy, though novel targeted agents have shown limited success so far.
MPI/Uni Cologne 8002 ,61-41 tpeS 8002 ,61-41 tpeS m ohkcotS ,ssergnoC OMSE dr33 mllohkcotS ,ssergnoC OMSE dr33 KU ,retsehcnaM KU ,retsehcnaM ertneC gn gamI ra uce oM nosf oW ertneC gniigamI rallucelloM nosflloW z ohreH raK zllohreH llraK Imaging of glioma provides essential information for diagnosis, grading, treatment planning, and monitoring through techniques such as MRI, CT, PET, and MRS which characterize
FDG PET/CT Characteristics of Adrenal Benignand Malignant LesionsNicholas Plaxton
1. FDG PET/CT can help distinguish between benign and malignant adrenal lesions based on characteristics like size, Hounsfield units, and SUV. Lesions larger than 6 cm, with irregular shapes and heterogeneous uptake are more likely to be malignant.
2. Common primary malignant adrenal tumors include pheochromocytoma and leiomyosarcoma. Adrenal metastases are more common from lung cancer, breast cancer, renal cell carcinoma, and melanoma.
3. Benign adrenal lesions include adenomas, cysts, hyperplasia, myelolipomas, and lipomas which typically have lower Hounsfield units and SUVs than malignant lesions. However, characteristics can be variable so tissue
The Role of Surgery in Malignant
Pleural Mesothelioma presented by Harvey Pass, MD of NYU at the Mesothelioma Applied Research Foundation's conference in New York, NY on September 28, 2012. www.curemeso.org
The document summarizes a study comparing a new bombesin peptide antagonist (JMV4168) to agonists for targeting gastrin releasing peptide receptors (GRPR) overexpressed on prostate and breast cancers. In vitro assays showed JMV4168 bound primarily to the surface of prostate cancer cells, while agonists were more internalized. In vivo studies in mice found JMV4168 had high tumor uptake and fast clearance from GRPR-rich pancreas and background tissues, indicating its potential as a safer agent than agonists for clinical imaging and therapy of GRPR-overexpressing cancers.
Interpretare i risultati NIPT: i mosaicismi feto-placentari e le implicazioni sulla scelta tra amniocentesi o villocentesi come test di conferma dopo un risultato NIPT ad alto rischio / Interpreting NIPT results: feto-placental mosaicism and the implication on choice between confirmatory amniocentesis or CVS after a positive cfDNA testing result (F. R. Grati)
The document discusses high content genotoxicity screening using the IN Cell Analyzer 1000. It describes regulatory genotoxicity tests and an in vitro micronucleus assay that allows quantification of micronuclei induction, apoptosis, and cell proliferation in one well. The assay uses automated imaging and analysis for fast, objective scoring of micronuclei. It also discusses criteria for identifying micronuclei and compares automated and manual scoring. Finally, it compares two micronucleus assay formats and how they assess cytotoxicity.
Dr. masciotra shear wave elastography and more in a clinical case of multip...antonio pio masciotra
This is the presentation of a clinical case of Multiple Myeloma with a thorough discussion on many aspects of the disease and on applications of Shear Wave Elastography.
pleomorphic, sarcomatoid or
sarcomatous elements
The document discusses lung cancer (carcinoma pulmonar) and highlights several issues:
1) Lung cancer is stigmatized as being "self-inflicted" due to its strong association with tobacco use.
2) It receives little coverage in the media about treatment advances and attracts little celebrity interest.
3) Patients and families receive poor support from organizations and have pessimistic views of treatment outcomes held by doctors, patients, and families.
4) The document examines how oncologists treating lung cancer would choose to be treated themselves, finding increasing acceptance of chemotherapy over time.
Dr Ludmil B. Alexandrov - Carcinogenesis Young Investigator Award 2016Oxford University Press
The document discusses mutational processes in human cancer and methods for analyzing mutational signatures. It describes extracting 30 mutational signatures from the mutation catalogs of 12,023 cancer cases across 40 cancer types using non-negative matrix factorization. Certain signatures are found to dominate in specific cancer types, such as Signature 1 and Signature 5 in breast cancer. Clock-like mutational signatures accumulate with age and are present across individuals.
Protein Nanotube based Probes for Cancer Cell Imaging was the lecture delivered by Dr. H. S. Atreya at the one day seminar on Molecular Imaging conducted by Molecular Imaging Society of India 9-March-2014
This document discusses maintenance therapy options for patients with metastatic lung cancer. It summarizes several key clinical trials that evaluated continuation or switch maintenance strategies with drugs such as bevacizumab, pemetrexed, and erlotinib. Histology and molecular markers like EGFR mutations and ALK translocations are predictive of response to certain drugs. Ongoing trials are further exploring predictive biomarkers and sequential testing strategies to select the most effective treatment based on a patient's tumor characteristics. While maintenance therapy may delay tumor progression, it is still unclear if it provides a true survival benefit over second-line treatment administered at the optimal time.
This document discusses glioblastoma multiforme in a 67-year-old male patient. Key details include:
- The patient presented with a 4-week history of headaches and memory loss as well as right-sided weakness.
- MRI showed features consistent with a high-grade glioma such as necrosis, microvascular proliferation, and contrast enhancement.
- Glioblastoma is the most common and aggressive primary brain tumor, typically affecting adults around age 45-70. Median survival is less than 12 months even with optimal treatment.
- Treatment involves maximal surgical resection followed by radiation and chemotherapy with temozolomide, which has been shown to improve outcomes modestly. Ongoing
Sample Acquisition With Annotated Clinical Information: A Critical Success Factor In Biomarker Validation
The document discusses how sample acquisition with annotated clinical information is critical for biomarker validation and targeted drug development. It notes that most drugs fail due to lack of efficacy because they are not tested in targeted patient populations. Access to well-annotated specimens and analytical capabilities is an unmet need. The challenges of tumor heterogeneity are also discussed. Sample acquisition with clinical data allows for better understanding of targets and more effective clinical trials of companion diagnostics and targeted therapies.
Audio and slides for this presentation are available on YouTube: http://youtu.be/e_KVYJX2GTs
Have you ever wondered about your genetic predisposition to cancer? How cancer evolves in families? Or how cancer cells differ from normal cells in your body? Join Judy Garber, MD, MPH, director of the Center for Cancer Genetics and Prevention at Dana-Farber Cancer Institute, as she explores the basics of cancer genetics, DNA mutations, genetic screening, management, and more.
Dr. Charles Geyer, Jr., President & CMO of the Statewide Clinical Trials Network of Texas (CTNeT) discusses CTNeT (Statewide Clinical Trials Network of Texas) and its role in Building Texas' Life Sciences Infrastructure; Getting the Most Promising Science to the Most People at the 2012 CPRIT Innovation in Cancer Conference
The document discusses epigenetics and DNA methylation in oncology. It provides an introduction to epigenetics and how epigenetic modifications can regulate gene expression without changing DNA sequence. It then discusses using DNA methylation as an epigenetic biomarker for cancer, including prostate and bladder cancers. Specific methylated genes are highlighted as biomarkers for bladder cancer detection in urine samples from patients with hematuria. Validation study results show the biomarkers can accurately detect bladder cancer with high sensitivity and negative predictive value, reducing unnecessary cystoscopies.
This document provides an overview of breast cancer therapy. It discusses trends in breast cancer incidence in the United States, declining mortality rates, and treatment approaches for early stage disease including local and systemic therapies guided by risk assessment. Key aspects of risk assessment using tools like Oncotype DX are outlined. The roles of endocrine therapy and chemotherapy in adjuvant treatment are summarized, including evolving regimens and trial results demonstrating improved outcomes. Potential toxicities of different systemic therapies are also highlighted.
NSCLC: diagnóstico molecular, pronóstico y seguimiento; CTCMauricio Lema
Lo nuevo en diagnóstico molecular, pronóstico y seguimiento en NSCLC, y el impacto pronóstico de las Células Tumorales Circulantes. Para evento de cirugía de tórax, Hotel Intercontinental, Medellín, 22.05.2018 (se complementa con las la presentación de lo nuevo en terapia sistémica en NSCLC).
The document discusses MAGE genes, which code for tumor antigens recognized by cytotoxic T lymphocytes. It provides background on MAGE genes, including that they were first identified in melanoma in 1991. MAGE genes are expressed in various cancers but not most normal tissues. The expression of certain MAGE genes has been associated with prognosis in cancers like lung and prostate cancer. Immunotherapies targeting MAGE antigens show potential for cancer treatment by activating CD8+ T cells against tumor cells. However, the tumor microenvironment can also induce immune suppression, presenting a barrier to the clinical efficacy of cancer vaccines.
This document discusses genomic signatures that can predict the risk of metastasis in breast cancer. Specifically, it summarizes that the 70-gene MammaPrint profile and intrinsic subtypes can predict metastasis risk and guide adjuvant therapy. Additionally, these genomic profiles are often maintained throughout the metastatic process, from the primary tumor to distant metastases in various sites. However, while profiles predict metastasis risk, they cannot predict the specific site of metastasis. Intrinsic subtypes show non-random associations with certain metastasis sites.
The incidence of malignant pleural mesothelioma in Europe will peak between 2015-2020. Key molecular alterations involve inactivation of tumor suppressors p16 INK4A/p14ARF and NF2. Pemetrexed plus cisplatin is standard first-line chemotherapy. Vinorelbine may be used second-line. Selected patients benefit from multimodality therapy including neoadjuvant chemotherapy, extrapleural pneumonectomy, and potentially radiotherapy, though novel targeted agents have shown limited success so far.
MPI/Uni Cologne 8002 ,61-41 tpeS 8002 ,61-41 tpeS m ohkcotS ,ssergnoC OMSE dr33 mllohkcotS ,ssergnoC OMSE dr33 KU ,retsehcnaM KU ,retsehcnaM ertneC gn gamI ra uce oM nosf oW ertneC gniigamI rallucelloM nosflloW z ohreH raK zllohreH llraK Imaging of glioma provides essential information for diagnosis, grading, treatment planning, and monitoring through techniques such as MRI, CT, PET, and MRS which characterize
FDG PET/CT Characteristics of Adrenal Benignand Malignant LesionsNicholas Plaxton
1. FDG PET/CT can help distinguish between benign and malignant adrenal lesions based on characteristics like size, Hounsfield units, and SUV. Lesions larger than 6 cm, with irregular shapes and heterogeneous uptake are more likely to be malignant.
2. Common primary malignant adrenal tumors include pheochromocytoma and leiomyosarcoma. Adrenal metastases are more common from lung cancer, breast cancer, renal cell carcinoma, and melanoma.
3. Benign adrenal lesions include adenomas, cysts, hyperplasia, myelolipomas, and lipomas which typically have lower Hounsfield units and SUVs than malignant lesions. However, characteristics can be variable so tissue
The Role of Surgery in Malignant
Pleural Mesothelioma presented by Harvey Pass, MD of NYU at the Mesothelioma Applied Research Foundation's conference in New York, NY on September 28, 2012. www.curemeso.org
The document summarizes a study comparing a new bombesin peptide antagonist (JMV4168) to agonists for targeting gastrin releasing peptide receptors (GRPR) overexpressed on prostate and breast cancers. In vitro assays showed JMV4168 bound primarily to the surface of prostate cancer cells, while agonists were more internalized. In vivo studies in mice found JMV4168 had high tumor uptake and fast clearance from GRPR-rich pancreas and background tissues, indicating its potential as a safer agent than agonists for clinical imaging and therapy of GRPR-overexpressing cancers.
Interpretare i risultati NIPT: i mosaicismi feto-placentari e le implicazioni sulla scelta tra amniocentesi o villocentesi come test di conferma dopo un risultato NIPT ad alto rischio / Interpreting NIPT results: feto-placental mosaicism and the implication on choice between confirmatory amniocentesis or CVS after a positive cfDNA testing result (F. R. Grati)
The document discusses high content genotoxicity screening using the IN Cell Analyzer 1000. It describes regulatory genotoxicity tests and an in vitro micronucleus assay that allows quantification of micronuclei induction, apoptosis, and cell proliferation in one well. The assay uses automated imaging and analysis for fast, objective scoring of micronuclei. It also discusses criteria for identifying micronuclei and compares automated and manual scoring. Finally, it compares two micronucleus assay formats and how they assess cytotoxicity.
Dr. masciotra shear wave elastography and more in a clinical case of multip...antonio pio masciotra
This is the presentation of a clinical case of Multiple Myeloma with a thorough discussion on many aspects of the disease and on applications of Shear Wave Elastography.
pleomorphic, sarcomatoid or
sarcomatous elements
The document discusses lung cancer (carcinoma pulmonar) and highlights several issues:
1) Lung cancer is stigmatized as being "self-inflicted" due to its strong association with tobacco use.
2) It receives little coverage in the media about treatment advances and attracts little celebrity interest.
3) Patients and families receive poor support from organizations and have pessimistic views of treatment outcomes held by doctors, patients, and families.
4) The document examines how oncologists treating lung cancer would choose to be treated themselves, finding increasing acceptance of chemotherapy over time.
Dr Ludmil B. Alexandrov - Carcinogenesis Young Investigator Award 2016Oxford University Press
The document discusses mutational processes in human cancer and methods for analyzing mutational signatures. It describes extracting 30 mutational signatures from the mutation catalogs of 12,023 cancer cases across 40 cancer types using non-negative matrix factorization. Certain signatures are found to dominate in specific cancer types, such as Signature 1 and Signature 5 in breast cancer. Clock-like mutational signatures accumulate with age and are present across individuals.
Protein Nanotube based Probes for Cancer Cell Imaging was the lecture delivered by Dr. H. S. Atreya at the one day seminar on Molecular Imaging conducted by Molecular Imaging Society of India 9-March-2014
This document discusses maintenance therapy options for patients with metastatic lung cancer. It summarizes several key clinical trials that evaluated continuation or switch maintenance strategies with drugs such as bevacizumab, pemetrexed, and erlotinib. Histology and molecular markers like EGFR mutations and ALK translocations are predictive of response to certain drugs. Ongoing trials are further exploring predictive biomarkers and sequential testing strategies to select the most effective treatment based on a patient's tumor characteristics. While maintenance therapy may delay tumor progression, it is still unclear if it provides a true survival benefit over second-line treatment administered at the optimal time.
This document discusses glioblastoma multiforme in a 67-year-old male patient. Key details include:
- The patient presented with a 4-week history of headaches and memory loss as well as right-sided weakness.
- MRI showed features consistent with a high-grade glioma such as necrosis, microvascular proliferation, and contrast enhancement.
- Glioblastoma is the most common and aggressive primary brain tumor, typically affecting adults around age 45-70. Median survival is less than 12 months even with optimal treatment.
- Treatment involves maximal surgical resection followed by radiation and chemotherapy with temozolomide, which has been shown to improve outcomes modestly. Ongoing
Sample Acquisition With Annotated Clinical Information: A Critical Success Factor In Biomarker Validation
The document discusses how sample acquisition with annotated clinical information is critical for biomarker validation and targeted drug development. It notes that most drugs fail due to lack of efficacy because they are not tested in targeted patient populations. Access to well-annotated specimens and analytical capabilities is an unmet need. The challenges of tumor heterogeneity are also discussed. Sample acquisition with clinical data allows for better understanding of targets and more effective clinical trials of companion diagnostics and targeted therapies.
Audio and slides for this presentation are available on YouTube: http://youtu.be/e_KVYJX2GTs
Have you ever wondered about your genetic predisposition to cancer? How cancer evolves in families? Or how cancer cells differ from normal cells in your body? Join Judy Garber, MD, MPH, director of the Center for Cancer Genetics and Prevention at Dana-Farber Cancer Institute, as she explores the basics of cancer genetics, DNA mutations, genetic screening, management, and more.
Dr. Charles Geyer, Jr., President & CMO of the Statewide Clinical Trials Network of Texas (CTNeT) discusses CTNeT (Statewide Clinical Trials Network of Texas) and its role in Building Texas' Life Sciences Infrastructure; Getting the Most Promising Science to the Most People at the 2012 CPRIT Innovation in Cancer Conference
The document discusses epigenetics and DNA methylation in oncology. It provides an introduction to epigenetics and how epigenetic modifications can regulate gene expression without changing DNA sequence. It then discusses using DNA methylation as an epigenetic biomarker for cancer, including prostate and bladder cancers. Specific methylated genes are highlighted as biomarkers for bladder cancer detection in urine samples from patients with hematuria. Validation study results show the biomarkers can accurately detect bladder cancer with high sensitivity and negative predictive value, reducing unnecessary cystoscopies.
This document provides an overview of breast cancer therapy. It discusses trends in breast cancer incidence in the United States, declining mortality rates, and treatment approaches for early stage disease including local and systemic therapies guided by risk assessment. Key aspects of risk assessment using tools like Oncotype DX are outlined. The roles of endocrine therapy and chemotherapy in adjuvant treatment are summarized, including evolving regimens and trial results demonstrating improved outcomes. Potential toxicities of different systemic therapies are also highlighted.
NSCLC: diagnóstico molecular, pronóstico y seguimiento; CTCMauricio Lema
Lo nuevo en diagnóstico molecular, pronóstico y seguimiento en NSCLC, y el impacto pronóstico de las Células Tumorales Circulantes. Para evento de cirugía de tórax, Hotel Intercontinental, Medellín, 22.05.2018 (se complementa con las la presentación de lo nuevo en terapia sistémica en NSCLC).
The document discusses how life translates genetic information from the genome into an organism's phenotype given its environment. It states that the organism computes its phenotype from its genotype in a specific environment. Genome information is translated into the observable characteristics of an organism.
Cetuximab was evaluated as:
1) Monotherapy for recurrent/metastatic SCCHN after platinum failure
2) In combination with radiotherapy for locally advanced SCCHN
3) In combination with chemotherapy as first-line treatment for recurrent/metastatic SCCHN
The document discusses circulating tumor cells (CTCs) in lung cancer and summarizes some key challenges and applications. It notes that CTCs can be detected and enumerated using the FDA-approved CellSearch system, but this only captures EpCAM+ CTCs. Emerging technologies like ISET aim to detect a broader range of CTC subtypes. Studies show CTC counts correlate with stage and prognosis in lung cancer and may serve as pharmacodynamic biomarkers of treatment response. Characterizing CTC phenotypes like epithelial-mesenchymal transition could provide insights into metastasis. Circulating tumor microemboli are also detected in some patients and may help tumor cells survive in circulation.
Microarrays allow researchers to examine gene expression patterns across thousands of genes simultaneously. A microarray contains probes for known genes that are used to detect complementary mRNA in a biological sample. Microarrays can be used to study gene expression differences between normal and diseased tissues, classify tumor subtypes, and diagnose cancers. They also show promise for personalized cancer treatment by predicting patient prognosis and response to therapy.
This document discusses thyroid cancer, the most common endocrine malignancy. It accounts for about 3% of cancers and is six times more common in women. The prognosis is excellent for most patients, with an overall 10-year survival rate of 85%. Differentiated thyroid cancers including papillary, follicular, and Hurthle cell carcinomas comprise over 90% of cases and have very favorable outcomes. Despite their generally good prognosis, local recurrence occurs in up to 20% of patients and distant metastases in about 10% at 10 years. Initial management involves surgical removal of the thyroid gland followed by radioactive iodine in most cases.
The document discusses how cancer genomics is transforming cancer diagnosis. Next-generation sequencing technologies are enabling whole genome and exome sequencing of tumors at lower costs. This allows comprehensive genomic profiling of cancers to detect mutations, rearrangements, and biomarkers that provide diagnostic, prognostic and treatment information. However, challenges remain around technology, costs, data analysis and clinical integration. Pathologists will need to adapt training and integrate genomic data into diagnostic reporting to realize the potential of cancer genomics.
Alain Toledano : Test and genomic profile : what future in breast cancer trea...breastcancerupdatecongress
This document summarizes a study that used whole-genome sequencing and molecular pathological analysis to track the evolution of the lethal prostate cancer cell clone in a patient who died from metastatic prostate cancer. The analyses revealed that the lethal clone arose from a small, relatively low-grade cancer focus in the primary tumor, not the bulkier higher-grade primary tumor or a lymph node metastasis removed during prostatectomy. This highlights the importance of molecular markers to better predict cancer progression and underscores the need to longitudinally sample metastatic lesions to understand clonal evolution during disease progression. Similar comprehensive studies of additional prostate cancer cases are needed.
This document summarizes prostate cancer detection, prognosis, treatment options, and future directions. It discusses standard therapies including surgery, radiation, hormone therapy, chemotherapy, and bone-targeted therapy. Emerging immunotherapies and clinical trials of new agents such as abiraterone and MDV3100 are also reviewed. The disease continuum moves from localized to advanced disease, and treatments aim to target different stages from non-metastatic to castration-resistant prostate cancer.
The document summarizes a presentation on bioinformatics case studies focusing on epigenetics and personal genomics. It discusses DNA methylation and its role in cancer development. It also describes how next-generation sequencing can be used to identify epigenetic biomarkers for clinical use. Finally, it addresses issues around personal and recreational genomics, including increasing access, educating users, and protecting individual privacy and rights.
1) Traditional breast cancer classification uses pathology and immunohistochemistry to assess grade, receptors, and proliferation, while molecular classification analyzes subtypes using gene, epigenetic, RNA, and protein expression data.
2) Integrating multiple types of omics data provides more comprehensive characterization of tumors and can identify clinically targetable pathways for personalized treatment.
3) For triple negative breast cancer, molecular subtyping further divides patients into basal, luminal, and claudin-low subgroups with differences in prognosis, drug sensitivity, and immune context.
This document summarizes new approaches for head and neck cancer, including robotic surgery, proton radiotherapy, biomarkers like HPV and PD-L1 status, genomic profiling, and immunotherapy like nivolumab and pembrolizumab. It shows that immunotherapy such as nivolumab has better outcomes for HPV-positive head and neck cancer patients compared to standard chemotherapy. PD-L1 expression is also associated with better outcomes from pembrolizumab and nivolumab treatment. Combining cetuximab with chemotherapy improves survival compared to chemotherapy alone in recurrent/metastatic head and neck cancer. Pembrolizumab demonstrates superior overall survival compared to standard of care for recurrent/metastatic head and neck
Cancer-associated VTE is a critical complication in patients with cancer. However the pathological findings of VTE are limited. Here are investigated the histopathological features of cancer-associated VTE in human autopsy cases.
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TriStar Technology Group Corporate Presentation
1. Sample Acquisition With
Annotated Clinical Information
A Critical Success Factor In Biomarker Validation
TriStar
Technology Group
9700 Great Seneca Highway, suite 401
Rockville, MD 20850
(E) info@tristargroup.us
(P) 301-792-633
(W) www.tristargroup.us
2. the need for targeted therapeutics
with companion diagnostics
Development of targeted therapeutics requires testing in targeted populations
matched to a drug’s mechanism of action
Evaluation of Trastuzamab in “all comer” breast cancer patients (25% HER+,
75% HER2-) would not have shown significant benefit in clinical trials
Early proof of concept in the right patient population is crucial
Potentially shorter time to market
3. An emerging unmet need in oncology drug
development today is service providers
that offer both access to well-annotated
specimens and sophisticated molecular
analytical capabilities
4. Rockville, MD Hamburg, Germany
TMA Repository
Array Manufacturing
Contract Research
Madrid, Spain Rome & Catania, Italy
TMA Repository TMA Repository & Contract Research
Cancer Stem Cell Research
5. tristar provides
Access to 2.5 million archived samples & clinical data
Access to patients (prospective collection projects)
Fit-for-purpose analytical platforms & services (IHC, FISH, qRT-
PCR etc.)
Collaboration for Solid tissue biomarker development
6. ethical considerations
Informed Donor Consent
IRB/EC Approval
Fully Anonymized
Compliant with Current International & EU Regulations
Blocks That Are in Excess of Diagnostic Sample Only
Team of 17 Pathologists & 5 Oncologists for Clinical Data Review
7. product groups
Archived Human Tissue Repository
>2.5 million samples (FFPE & Frozen). 70% Oncology, 30% CNS, GI etc.
High-Density Tissue Micro Arrays
>100,000 donor samples with outcome data
Outcome Data
Treatment, Response rates, disease –free survival (DFS), overall survival (OS)
Molecular Data
ER/PR/HER2, p53, BRAF, KRAS, EGFR, PIK3CA etc.
Blocks & Large sections
With matching RNA, DNA
Cancer Stem Cell Arrays
Lysates & RNA
8. our services
Protein Expression
IHC (Antibody protocol development, automated or manual staining, reading & interpretation)
Large-Scale Analysis of Prognostic markers (500-3500 donor samples)
(500-3500 donor samples)
Gene Expression
RT-PCR
Gene copy number
FISH/CISH
Gene sequencing
DNA sequencing
Cross-Reactivity Screening in Normal Tissue
(GLP)
9. quality control
Samples are fixed/frozen within 2 – 10 minutes of
Excision
OCT embedded sample
Snap frozen sample
Formalin fixed sample
10. quality control
10% Buffered formalin, 10-12 hrs. fixation time
Morphology (H&E) & IHC Markers for
immunogenicity
RNA & DNA Quality (Agilent 2100 Bioanalyzer)
RIN can be checked & provided upon request
11. primary tumors
with matched mets
Primary Tumors Matched Mets Approximate number
Nodal 2000
Breast Distant 20
Bone 200
CRC Nodal 2000
Liver 150
Prostate Nodal 500
Bone 300
Lung (NSCLC) Nodal 300
Bone 100
Pancreatic Nodal 100
Head & Neck Nodal/Soft tissue 100
Gastric Nodal, liver etc 200
Melanoma Nodal 50
12. samples with outcome data
tumor type data approximate number
5 yr survival 5000
Breast 10 yr. survival 300
Herceptin 400 (responders & non-responders)
3-5 yr survival 4000
CRC
Bevacizumab, Cetuximab 500 (responders & non-responders)
Prostate, 10 yr survival 5000
Breast, CRC, Ovarian SOC Chemotherapy 1500 (responders & non-responders)
3-5 yr survival 2000
Lung (NSCLC)
Docetaxel, Gemcitabine 400
Pancreatic Survival 350
Head & Neck Treatment/survival 200
Gastric Survival 250
NHL Survival 200
Ovarian 3-5 yr. survival 300
Bladder Survival 500
13. tissue microarrays
Morphology
Formalin Fixed
Paraffin Embedded
RNA/Protein/DNA
Frozen OCT Embedded DNA
14. tissue microarrays to study tumor
heterogeneity
The whole tumor is sectioned Cores are taken from each constituent tumor
into 8-10 constituent blocks block and transferred to a TMA.
The exact localization of each
block is recorded
15. tissue microarrays to study tumor
heterogeneity
An optimal way to measure intratumoral heterogeneity
Allows for an overview of the whole tumor
Matched Nodal Total number of
Tumor Type Primary tumors Blocks per tumor Blocks per met
Mets TMA Cores
NSCLC 146 8 66 4 1432
Breast 147 8 32 4 1304
CRC 140 8 42 4 1288
Prostate 190 10 - - 1900
Bladder 147 8 - - 1176
16. EGFR amplification is often
heterogeneous in lung cancer
Heterogeneity found in 7/13 (54%) EGFR amplified NSCLC
Different areas Different matched
of the primary cancer lymph node metastases
Case
#1
EGFR FISH Result
#2
#3 amplification
#4 polysomy
#5
normal
#6
#7 n.a.
17. heterogeneity TMA: co-analysis of ERG and
PTEN in prostate cancer
35 ERG+PTEN
10 PTEN only
4 ERG only
PTEN linked to ERG
31 tumors PTEN+ERG
21 ERG precedes PTEN
0 PTEN precedes
PTEN deletions are late events developing ERG earlier
preferentially in ERG positive prostate
cancers PTEN + ERG
PTEN only
ERG only
P<p<0.0001
18. prostate cancer progression &
prognosis analysis
Frequency of PTEN deletion is strongly linked to prostate cancer
progression (n >2200 donor samples)
50.0 p<0.0001
45.0
40.0
fraction of tumors (%)
35.0 PTEN homozygous
30.0
25.0 PTEN hemizygous
20.0
15.0
10.0
5.0
0.0
PIN (n=29) BPH (n=20) pT2 pT3a pT3b pT4 (n=24) HR (n=54)
(n=1085) (n=360) (n=227)
19. tissue micro arrays to study
tumor heterogeneity
The level of heterogeneity of therapy target genes may be relevant for
diagnosis and response
HER2 is homogenous in breast cancer but heterogeneous in colon cancer
Tumor heterogeneity is clinically important and can be optimally addressed
by heterogeneity TMAs
20. molecular epidemiology
Most oncology drugs in development are expected to be active only
in sub-sets of patients
How frequent is expression in human cancer?
Specific cancer subtypes or biological properties?
-prognostic relevance
What normal tissues do express target?
Option 1: Option 2:
Review the Perform
literature own studies
21. TriStar: a new dimension in
tissue biomarker analysis
Prognosis TMA-Based Target Evaluation Strategy (IHC)
Multi-Tumor Tissue Array Normal Tissue Array Tumor Cell Line Array
3,500 donor samples 600 donor samples 140 Cell Lines
All Cancer Types 532 Cell Types Including NCI 60
√ Expression in cancer types (including niche cancers)
√ Complete normal tissue expression information
√ Cell lines identified for functional studies/drug screening
Cancer – Specific Prognosis TMA Analaysis
Prostate Cancer Breast Cancer Lung Cancer Bladder Cancer
(3,000 donors) (2,000 donors) (1,400 donors) (1,100 donors)
Colon Cancer Pancreatic Cancer Ovarian Cancer NHL
(1,400 donors) (300 donors) (200 donors) (200 donors)
Relationship of Molecular Target to Prognosis, Histological Sub-type,
Response to Treatment etc
23. HER2 Expression and Amplification
in Human Cancers
Tapia et al., Modern Pathology, 20(2), 192–198 (2007)
IHC FISH
Urinary bladder cancer
Pancreatic cancer
Endometrial cancer
Gall bladder cancer
Ovarian cancer
0.0 5.0 10.0 15.0 20.0
Fraction of HER2-amplified samples (%)
33. study: sequencing of all 10 PTEN exons in
100 prostate cancer samples
a) c.1067_1070del c) c.1623G>T e) c.352C>T
G C AG AAAC AAAAG G GATGTTTGAAACTAT GCTTTGTCAAGATCA
b) c.2007G>A d) c.1981_1984del
- 5% Mutations
GCAACATGATTGTCA TAAAGTAAGTACTAG
- Mutation Unrelated To Deletion
ABI3100, 16 capillaries tumor type data approx. # p value
Eppendorf pipetting robot PTEN not deleted 95.4% 4.6% 0.3096*
Laser capture micro dissection
(if necessary) PTEN hemizygous
deleted 17 11.8%
UKE data FISH not analyzable 18 0.0%
34. sample data fields
Breast Cancer with Herceptin Treatment & Response Information
LOCALISATION REF# ORGAN UNIQUE ID AGE DATE OF SURGERY DIAGNOSIS
METS POST SURGERY
GRADE T N M (TIME 0) STAGE HER2 ER (%) PR (%) SITE OF MET. METS DIAGNOSIS BY
(MONTHS)
PREV. START TREAT 1 END START TREAT 2 FOLLOW UP
SETTING END TREAT 2 FOLLOW UP 1 FOLLOW UP 2 SURVIVAL
CHEMOTH. TREAT 1 DETAILS TREAT 1 TREAT 2 DETAILS 3
35. sample prospective
collection projects
Prospective collection of formalin fixed samples of mantle cell lymphoma from
lymph node sites only with 5-10ug matching RNA per sample
Prospective collection of Frozen OCT & FFPE samples of IBD & Ulcerative Colitis,
recently diagnosed, diseased + adjacent normal. Matched Serum & Whole Blood
with Clinical Labs
Prospective collection of formalin fixed & OCT samples of metastatic NSCLC
(adenocarcinoma & SCC) with matched nodal mets, serum & RNA
Prospective collection of formalin fixed & OCT samples of esophageal
adenocarcinoma, serum & RNA
36. overview
Complexity of translational biomarker research supporting drug & diagnostic
development increasingly requires knowledge-based services/partnerships that
go beyond the traditional fee-for-service model
Service providers must offer a range of services, histology labs, analytical
platforms, top academic opinion leaders etc.
TriStar’s service platform is sustainable, scalable, flexible & cost-effective
Very large product offering, standardized QC, top-notch scientific capabilities
37. contact us
TriStar Technology Group LLC
9700 Great Seneca Highway
Rockville, MD 20852
For more information please visit our
website at www.tristargroup.us
p. 1-866-851-STAR
f. 1-509-471-1765
e. info@tristargroup.us
Editor's Notes
To change the grid imageOpen the file “home_image.psd”, add your photo, save as pngReturn to Power Point - select the photo, Right Click – Change Picture – Select the new photo
To change the team image1. Inside the group select the circle – Right Click > Format Picture/shape > Fill > Select option “Picture or texture fill” > select your photo and close!
To change the team image1. Inside the group select the circle – Right Click > Format Picture/shape > Fill > Select option “Picture or texture fill” > select your photo and close!
To change the team image1. Inside the group select the circle – Right Click > Format Picture/shape > Fill > Select option “Picture or texture fill” > select your photo and close!