Key points are not available for this paper at this time.
Introduction/Background Study of genetic alterations practical interests Understanding the molecular mechanisms of carcinogenesis Genetic risks (hereditary) Inherited mutations: BRCA1, BRCA2, PALB2... Biomarkers in clinical oncology screening diagnostic assistance prognosis prediction of response to treatment Development of new therapeutic approaches (targeted therapies) Methodology Biomarkers : Ability of the test to measure the biomarker with reliability and reproducibility Clinical utility Treatment decision can be based on test result (prospective study with test/objective) Clinical validity Ability of test to correlate with prognosis and/or response prediction (statistical significance) Molecule (protein or gene (DNA or RNA)) that influences tumor cell behavior and can predict prognosis and/or sensitivity/resistance to a specific treatment. Results PERSONALIZED MEDICINE PREVENTIVE STRATEGY personalized screening (example: predisposition to cancer) Prognostic criterion: -Which patient will do well without further treatment (natural history) example: chemo in breast cancer if risk of relapse Predictive criterion: -Which patient will do well with which type of treatment (example: hormone receptor positive and hormone therapy ) Therapeutic target: What molecular abnormality of the tumor can be targeted (example: HER2 overexpression and anti-HER2)? Biomarkers: genomic signatures -early breast cancer RH+/HER2- Prognostic value demonstrated Clinical validity: confirmed in large retrospective cohorts: Clinical utility: prospective evaluation of prognostic value and impact on therapeutic decisions (indication for adjuvant chemotherapy): Predictive criteria Predictive of what? Predictive of treatment efficacy Assumes that the treatment 'works' in certain subgroups and not in others: 'interaction' between the predictive factor and the treatment effect. Examples: Hormone receptors and hormone therapy HER2 and anti-HER2 Conclusion biomarkers Thanks to the development of molecular biology and high-throughput analysis, more and more markers are available to predict treatment efficacy. The 'mapping' of gene anomalies (overexpression, gene mutations) to predict efficacy or resistance to a given targeted therapy is the basis of personalized medicine in oncology. A large number of targeted therapies are thus inseparable from their 'companion' test, a predictor of their possible effect... The measurement of certain predictive 'biomarkers' can be repeated over time (iterative biopsies and/or 'liquid' biopsies) Disclosures The authors declare no conflict of interest.
Moctar et al. (Fri,) studied this question.