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Abstract
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.
