• Consensus on precision medicine for metastatic cancers: A report from the MAP conference.

      Swanton, C; Soria, J; Bardelli, A; Biankin, A; Caldas, C; Chandarlapaty, S; de Koning, L; Dive, Caroline; Feunteun, J; Leung, S; et al. (2016-05-03)
      Recent advances in biotechnologies have led to the development of multiplex genomic and proteomic analyses for clinical use. Nevertheless, guidelines are currently lacking to determine which molecular assays should be implemented in metastatic cancers. The 1(st) MAP conference was dedicated to exploring the use of genomics to better select therapies in the treatment of metastatic cancers. 16 consensus items were covered. While there was a consensus that new technologies like next-generation sequencing (NGS) of tumors and of ddPCR on circulating free DNA have convincing analytical validity, further work needs to be undertaken to establish both the clinical utility of liquid biopsies and the added clinical value of expanding from individual gene tests into large gene panels. Experts agreed that standardized bioinformatics methods for biological interpretation of genomic data are needed and that Precision Medicine trials should be stratified based on the level of evidence available for the genomic alterations identified.
    • Cyclooxygenase-dependent tumor growth through evasion of immunity.

      Zelenay, Santiago; van der Veen, A; Böttcher, J; Snelgrove, K; Rogers, N; Acton, S; Chakravarty, P; Girotti, Maria Romina; Marais, Richard; Quezada, S; et al. (2015-09-10)
      The mechanisms by which melanoma and other cancer cells evade anti-tumor immunity remain incompletely understood. Here, we show that the growth of tumors formed by mutant Braf(V600E) mouse melanoma cells in an immunocompetent host requires their production of prostaglandin E2, which suppresses immunity and fuels tumor-promoting inflammation. Genetic ablation of cyclooxygenases (COX) or prostaglandin E synthases in Braf(V600E) mouse melanoma cells, as well as in Nras(G12D) melanoma or in breast or colorectal cancer cells, renders them susceptible to immune control and provokes a shift in the tumor inflammatory profile toward classic anti-cancer immune pathways. This mouse COX-dependent inflammatory signature is remarkably conserved in human cutaneous melanoma biopsies, arguing for COX activity as a driver of immune suppression across species. Pre-clinical data demonstrate that inhibition of COX synergizes with anti-PD-1 blockade in inducing eradication of tumors, implying that COX inhibitors could be useful adjuvants for immune-based therapies in cancer patients.