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Bull Cancer. 2018 Apr;105(4):375-396. doi: 10.1016/j.bulcan.2018.01.009. Epub 2018 Mar 1.

[Precision medicine: A major step forward in specific situations, a myth in refractory cancers?]

[Article in French]

Author information

1
Groupe hospitalier mutualiste de Grenoble, institut de cancérologie Daniel-Hollard, 8, rue Docteur-Calmette, 38028 Grenoble cedex 1, France. Electronic address: n.albin@ghm-grenoble.fr.
2
Université Grenoble-Alpes, CHU de Grenoble, département d'anatomie et de cytologie pathologiques, unité fonctionnelle de pathologie moléculaire, pôle biologie, 38043 Grenoble cedex 9, France.
3
Groupe hospitalier mutualiste de Grenoble, institut de cancérologie Daniel-Hollard, 8, rue Docteur-Calmette, 38028 Grenoble cedex 1, France.

Abstract

In recent years, high-throughput sequencing techniques have been developed for cancerology and many clinical trials are currently structured around biomarkers that can guide specific treatment choices. This approach is characteristic of precision medicine, which is actually a concept initiated several decades ago with, for example, retinoic acid in promyelocytic leukemia. This paper will review the different types of molecular alterations and « -omics » biological analyses, bioinformatics tools, coupled drug/biomarkers already validated, the ethical issues of whole genomic sequencing of an individual as part of an inclusion in a clinical trial and finally the first results of precision medicine trials. The AcSé crizotinib program, supported by the Inca (french Cancer National Institute), is emblematic of a success of this personalized medicine illustrated by 4 points: the discovery of a cohort of patients with lung cancer with a ROS1 rearrangement characteristic of a sensitivity to crizotinib, a rapid availability of this innovation through the implementation of a temporary recommendation for use (ANSM), the obtention of a conditional marketing authorization by the pharmaceutical industry and finally, financial assumption of responsibility by French social security (HAS), despite preliminary and non-comparative data. In the case of cancers refractory to standard chemotherapy, and regarding our system of access to drugs illustrated by the PROFILER clinical trial, this approach allows the access to a therapeutic drug targeting specific biomarkers only in 7% of patients included. This does not bode well for efficient treatment and even less for survival. Allowing patients to be included in trials that identify molecular targets by molecular screening, and not being able to propose the drug of interest is a traumatic event for those patients who live in the hope of an immediate future. In refractory disease we must rethink precision medicine in a more humanistic vision for our patients and not only in a dimension of medico-industrial promotion. The implementation of a new multi-drug/multi-molecular target program could address this issue.

KEYWORDS:

Biomarkers; Biomarqueurs; Cancer; Mutations; Médecine de précision; NGS; Precision medicine

PMID:
29501208
DOI:
10.1016/j.bulcan.2018.01.009
[Indexed for MEDLINE]

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