dr. chirag desai , md, dm (oncology) hemato -oncology clinic, vedanta, ahmedabad
DESCRIPTION
Biotechnology in Fighting Fatal Disease – Cancer National Biotechnology Symposium 2012 Innovations in Biotechnology: From Education to Industry Sep 1, 2012, AMA, Ahmedabad. Dr. Chirag Desai , MD, DM (Oncology) Hemato -oncology Clinic, Vedanta, Ahmedabad. [email protected]. - PowerPoint PPT PresentationTRANSCRIPT
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Biotechnology in Fighting Fatal Disease Cancer
National Biotechnology Symposium 2012Innovations in Biotechnology: From Education to IndustrySep 1, 2012, AMA, Ahmedabad
Dr. Chirag Desai, MD, DM (Oncology)Hemato-oncology Clinic, Vedanta, Ahmedabad
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Metastatic colon cancer (unresectable)1970s Only 5-FU survival of 6 mths1980s Leucovorin/5-FU survival of 9 mths1990s Only 5-FU Addition of oxaliplatin/Irinotecan/capecitabine - survival of 18 mths2000s Avastin - survival of 21 mthsNow Erbitux survival of 25 mthsSurvival
Increased
4 folds
In
30 years
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Breast Cancer stage II1960s Only surgery - 40% cured1970s CMF - 50% cured1980s CMF and Tamoxifen - 60% cured1990s Anthracyclines and taxanes - 67% cured2000s Aromatase inhibitors - 73% curedNow Herceptin - 80% cured ??Cure
Rate
Doubled
In
40
years
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Biotechnology in Cancer:Translational ResearchBench to bedside
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The biological revolution of 20th century totally reshaped all fields of biomedical study -- cancer research being only one of them.
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Biotechnology helps in elucidating the normal cellular functioningAnd the derangements thereof resulting in diseaseIncluding cancer.andThe ways to tackle these derangements
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Chronic Myeloid LeukemiaOne cancerOne geneOne TreatmentOne chromosome
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Most CancersEach cancerMultiplegenesMultipleTreatmentsMultiple chromosomes
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InitiationNormal CellPre-Cancerous CellCancer CellInvasionAngiogenesisMetastasesSignal transductionMigrationSeed/SoilImmune SurveillancePromotion
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Prevention/early detectionDiagnosis/prognosisTreatment
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Biotechnology techniques and processes (Evans, P. R. Biotechnology and Biological Preparations in Encyclopaedia of PT vol. 1, 3rd edn.)
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Growth FactorGrowth Factor receptorSignal Transduction
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Research and development network
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Examples of Biologicals:Growth Factors:
EGFVEGFFGFIGFPDGFReceptors:
EGFRHer-2VEGFRPDGFRER/PRSTIs:
TKIsmTORICDKIFTIsOthers
Mabs:
RituximabAvastinHerceptinErbituxBiomab
clinicaloptions.com/oncologyProviding Personalized Care in an Era of Molecular Medicine
Evolution From Empiric to Personalized Therapy in NSCLCAdapted from Gandara DR, et al. Clin Lung Cancer. 2009;10:148-150.
FactorsAgent AffectedClinicalAsian, never-smoker, femaleErlotinib, gefitinibUntreated CNS metastases, no hemoptysis, uncontrolled hypertensionBevacizumabHistologicAdenocarcinoma Erlotinib, gefitinibNonsquamousBevacizumab, pemetrexedThymidylate synthasePemetrexedMolecularEGFR mutationErlotinib, gefitinibERCC1/RRM1PlatinumRRM1GemcitabineKRAS mutationErlotinib, gefitinib EGFR by FISHErlotinib? Gefitinib? EGFR by IHCCetuximab?EML4-ALK fusionCrizotinib
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Patient Selection Improves Treatment Results in NSCLCMedian survival (months)1970s1980s19902005BSC:24 monthsCisplatin-based regimens: 68 monthsPlatinum-based doublets (3rd gen): 810 months2005Bevacizumab + platinum-based doublet:>12 months282420161284020082008Pemetrexed+ platinum:>12 months
Bevacizumab + platinum:>14 monthsNon-squamousAdeno-onlyAdeno-onlyMolecular selection.EGFR-mut+Erlotinib alone>27 months2009/10No selection Clinical selection
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VEGF in clinicAntibody Bevacezumab (Avastin)Lung Cancer, Colon Cancer, Ovarian Cancer, Renal Cell Carcinoma, Brain Tumors, Breast Cancer
Tyrosine kinase Inhibitors:Sunitinib, Sorafenib, Pazopinib, Axitinib, Dovitinib, others
Renal Cell Cancer, Neuro-endocrine tumors, Liver cancers, GIST, Sarcoma
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Biologicals are effective in:
Lung cancerColon cancerBreast cancerHead and neck cancerLeukemias/LymphomasRenal/Liver cancersOthers
Biologicals help in the treatment of >80% of cancers either curatively or in advanced cancers
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Challenges in the development of biologicals
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RBF Symposium Feb 2011A Nobel Prize by Chance
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Start at the topFormulate testable hypothesisMake the plan / design the study
clinicaloptions.com/oncologyProviding Personalized Care in an Era of Molecular Medicine
Phase I(~ 18 mos)Phase II(~ 18 mos)Phase III(~ 36 mos)Preclinical(~ 18 mos) Total Time~ 90 mosor 7.5 yrsBiomarker IntegrationN = 30N = 300N = 1600DrugApprovalConfirm target
Assay developmentIntegrate biomarker
Assay performancePhases of Development of New Biomarker linked to New DrugBiomarkerinformative?
AssayperformanceClinical validation
CoprimaryendpointClinicalapplicationofbiomarkerGandara D, et al. NCI CAPR Workshop. 2011. Printed with permission.New Therapeutic Agent: Development Phases
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A large number of biologically/molecularly acting drugs are under developmentTraditional end points are less relevantNew end points requiredOS still is a gold standard end pointSurrogate end points need to be re-definedEven though response rate is less important, exact definition of response is criticalOngoing analysis of tissue/blood based biomarkers is critical
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Surrogate End points with targeted Therapies:
TraditionalPFSQoLOSPharmacoeconomicsOthers
ExploratoryTarget inhibitionTissue levelBlood levelPharmacogeneticTissue basedBlood based
clinicaloptions.com/oncologyProviding Personalized Care in an Era of Molecular Medicine
Primary endpoint: 8-wk disease control rate; 30% assumedKim ES, et al. AACR 2010. Abstract LBA1. Reprinted with permission.BATTLE: Phase II NSCLC Biomarker StudyUmbrella protocolCore biopsyEGFRKRAS/BRAF VEGFRXR/CyclinD1Biomarker profileRandomization: Equal AdaptiveErlotinib Equal (n = 25) Adaptive (n = 33)Vandetanib Equal (n = 23) Adaptive (n = 29)Erlotinib + Bexarotene Equal (n = 21) Adaptive (n = 15)Sorafenib Equal (n = 26) Adaptive (n = 72)
clinicaloptions.com/oncologyProviding Personalized Care in an Era of Molecular Medicine
Kim ES, et al. AACR 2010. Abstract LBA1. Reprinted with permission.BATTLE: Phase II NSCLC Biomarker StudyDiscovery Platform
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Who should do this?Academic institutions
Corporate hospitals
Individual practitioners
Medical associations
Collaborative effort
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Who should do this?
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Future:
Tests like Oncotype Dx21 in breast cancerDrugs like Imatinib in CMLOutcome like sequential use of chemo and targeted drugs in myelomaMaking cancer a chronic Disease
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**CNS, central nervous system; FISH, fluorescent in-situ hybridization; IHC, immunohistochemistry; NSCLC, non-small-cell lung cancer.**NSCLC, non-small-cell lung cancer.NSCLC, non-small-cell lung cancer.**