Evolutionary dynamics of cancer in response to targeted combination therapy

A partir de données initiales portant sur 20 patients atteints d'un mélanome traité à l'aide de vemurafenib, puis validée sur un ensemble complémentaire de patients atteints d'un mélanome, d'un cancer du pancréas ou du côlon-rectum, cette étude évalue l'intérêt d'un modèle mathématique permettant de prédire la réponse à une combinaison de deux ou trois thérapies ciblées

Résumé en anglais

In solid tumors, targeted treatments can lead to dramatic regressions, but responses are often short-lived because resistant cancer cells arise. The major strategy proposed for overcoming resistance is combination therapy. We present a mathematical model describing the evolutionary dynamics of lesions in response to treatment. We first studied 20 melanoma patients receiving vemurafenib. We then applied our model to an independent set of pancreatic, colorectal, and melanoma cancer patients with metastatic disease. We find that dual therapy results in long-term disease control for most patients, if there are no single mutations that cause cross-resistance to both drugs; in patients with large disease burden, triple therapy is needed. We also find that simultaneous therapy with two drugs is much more effective than sequential therapy. Our results provide realistic expectations for the efficacy of new drug combinations and inform the design of trials for new cancer therapeutics. - See more at: http://elife.elifesciences.org/content/2/e00747#sthash.JjFDg6Sf.dpuf