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Personalized medicine and oncosurgery

Personalized medicine and oncosurgery. O .Topolčan, V. Třeška. Teaching Hospital Plzeň, Faculty of Medicine in Plzeň, Charles University in Prague Czech Republic. Presentation structure. Personalized medicine and cancer Clinical use of biomarke r s assessment Our results

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Personalized medicine and oncosurgery

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  1. Personalized medicine and oncosurgery O.Topolčan, V. Třeška Teaching Hospital Plzeň, Faculty of Medicine in Plzeň, Charles University in PragueCzech Republic

  2. Presentation structure • Personalizedmedicineandcancer • Clinical use of biomarkers assessment • Our results • Conclusions for clinical practice • Final goal

  3. Todays x personalized • Todaysdiagnostics • Fromsymptoms to diagnosis • Empiricorcausaltherapy Personalizedmedicine • Moleculardiagnostic – biomarkers, genomic, • - omixmethod • Therapystratifed - individualised

  4. Impact of MolecularDiagnostics on theManegement of Cancer • Clasficacation of cancer • Risk assesmentandprognosis • Prediction of response to treatment • Guide to therapeutics

  5. Clasification of cancer • Analysis of RNA splicingevent in cancer • Cancerclassificationusingmicroarrays • Cancerstratificationbased on methlation markers • Analysis of chromosomalalteration of cancercells • Detection of loss of hererozigosity (LOH) • Diagnosis of cancer of anunkownprimary • Diagnosticsfordetection of minimalresidualdisease

  6. Risk asesmentandprognosis • Cancerprognosis • Detection of mutationsfor risk asessmetandprevention

  7. Prediction of responce to treatment • Biopsytesting of tumorsforchemotherapy sensitivity • Genomicanalysis of tumor biopsies to predict response to treatment • Serumnucleosides as indicators of sensitivity as chemotherapy • Testingmicrosatelliteinstabililityforrespose to chemotherapy • Prediction of response to radiationtherapy

  8. Guide to therapeutics • Diagnosticsfordetection of Multidrugresistency • Detection of resistence to chemotherapy • Moleculardiagnosticscombinedwithcancertherapeutics • Drugdiscoveryanddevelopment • Design of futurecancertherapies • Screeningforpersonalizedanticancerdrug • Pharmacogenomic test forstratification of clinicaltrials

  9. Current status • Routine • Biomarkers = tumor markers • High PPV, Low NPV, Low sensitivity andspecicifity • Indication • Follow-up of cancer disease

  10. Ourreults Metastatic proces in Liver

  11. New ourapproachforClinical use of biomarkers • Targetquestionandtargetbiomarkers • Multidiscplinedapproach • Multiparametrdiagnostics • Multiplex andOptimal therapy choice of surgery procedure

  12. Metastasisresection • Preoperativandpooperativfor prognosis: • Tumor markers CEA, CA 19-9, cytokeratins, • AngiogenoticfactorOPR, OPN, PRL, VEGF, • GrowthfactorHGF, IGF -1, IGFBP 3, 7 • MMP 7, 9 TIMP-1 • Gene expression K-ras, p53, HER-2 neu, TIMP-1, MMP 7, 9 Predictionforprogresion • CEA, circulating cancer cells or circulating DNA • D vitamine

  13. RFA • Preoperativandpooperativfor prognosis: • Tumor markers CEA, CA 19-9, cytokeratins, • AngiogenoticfactorOPR, OPN, PRL, VEGF, • GrowthfactorHGF, IGF -1, IGFBP 3, 7 • MMP 7, 9 TIMP-1 • Gene expression K-ras, p53, HER-2 neu, TIMP-1, MMP 7, 9 Predictionforprogresion • CEA, circulating cancer cells or circulating DNA • D vitamine cytokeratine

  14. Portalveinembolism • Aimfor vyšetření – predictterapeuticeffect • goodresponce – regeneration • poorresponce - minimalgrowth • Tumor progresion

  15. Portalveinembolism • Imaing technik – expensiv, slowchangis • Markes – research – in ourlaboratory • Cytokeratins • Cytokains – inflamatory IL • Angiogenetics – OPG, OPN • Growth IGF-1

  16. IGF -1 • Anti-apoptotic activity • Mitotic activity • MMP-7 activation • IGFBP3 inhibition • Correlation between IGF1 and Multidrug Resistance-Associated Protein-1 (MDR -1) • Inverse correlation with adiponectin

  17. Adiponectin • Breast cancer • MMP-7 inhibition, favorable prognosis • Anti-angiogenetic effect • Gastric cancer • Angiogenesis inhibition, • apoptosis activation, favorable prognosis • Prostate cancer • Controversial results

  18. Prolactin • Angiogenesis stimulation • Adhesion molecules stimulation • Metastatic potentiating of tumor • CRC - unfavorable prognosis

  19. Why do we need this knowledge • Prevention • Diagnostics • Prognosis estimation • Follow-up • Therapy • Optimal therapy choice • New therapy choice – personalized medicine

  20. Prevention Targeted prevention • Active screening of patients for the risk of cancer occurence • Stratificationpopulation • Targeted prevention method • Targeted prevention monitoring

  21. Diagnosis ! Not (so far) ? Hopefully in future ??

  22. Prognosis a prediction • Prognosis preoprativfor DFI and OS • Prediction of surgeryeffectfordiferent type operationion • Residual • Postoperativchekingandprognosisfor DFI and OS • Follow-upandpredictionrelaps • Early detection of disease progression

  23. Final goal • Improvement to the quality of life of cancer patients • DFI and OS extension

  24. Thank you for your attention

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