Using somatic mutations to guide treatment decisions: Context matters
Cet article passe en revue les travaux récents suggérant l'intérêt de prendre en compte des informations sur le contexte cellulaire pour mieux orienter un choix thérapeutique à partir d'informations sur les mutations somatiques
Mutations and other somatic genomic abnormalities are commonly used to inform treatment decisions. Such molecularly based personalized treatment strategies were until recently limited to an assortment of rare tumor types or molecularly defined subtypes of common cancers. Lately, these strategies have expanded to other tumor types, in particular lung cancer and melanoma. Although the approach to genomic-based treatment decisions has been broadly embraced, provision of a targeted agent to a patient whose cancer harbors the genomic target rarely leads to cure, and sometimes responses are incomplete. Also, opportunity costs for patients and the expenses of ineffective treatments are great; therefore, improvements are needed in the effective clinical use of mutation data. Although patients do benefit from today’s approach to interpreting mutation data, we propose that interpretive strategies considering both cellular and genomic context of mutations will provide a more accurate rationale for treatment decisions (Figure). Cellular context accounts for histologic etiology and how cell type–specific differences in cellular signaling impact treatment success. Genomic context includes 3 distinct considerations: (1) clonal diversity of cancer cell populations and resulting evolution induced by treatment, (2) the presence of resistance mutations or other genomic features that preclude effective targeting of a mutation treatment efficacy barriers), and (3) the driver or activation status of the mutation at the time of treatment.
JAMA Oncology , article en libre accès, 2014