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10/01/2017

Recent review calls for a multi-molecular approach to developing novel anti-colorectal cancer therapies based on established subtypes

Published online last week in Nature Reviews Cancer, lead co-authors of the review, Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer, Josep Tabernero, Director of VHIO, and Rodrigo Dienstmann, Principal Investigator of VHIO´s Oncology Data Science (ODysSey) Group, and Research Scientist, Computational Oncology Group, Sage Bionetworks (Seattle, USA), explore the current scenario of translational research in CRC firmly set within the context of precision medicine.

Commencing with the mapping of the early beginnings aimed at unravelling the various mechanisms implicated in the development and progression of CRC, the review goes on to trace the genomic-based successes in furthering insights into the molecular make-up of CRC. Discussing the complex heterogeneity across the recently defined four consensus molecular subtypes (CMS) of this disease*, the authors expertly underline both the challenges and opportunities that lie ahead in ultimately putting the brakes on the molecular culprits that drive tumor initiation, development, and growth in each individual CMS group.

Just some of those opportunities under the lens in the review surround the advent of positive predictive markers for targeted therapies including infrequent genomic events as well as promising biomarkers for novel immune checkpoint inhibitors including microsatellite instability and POLE mutations in CRC.

Commenting for VHIO Communications, Rodrigo Dienstmann observes, “To more effectively deliver transformative medicine against colorectal cancer we must continue to finely tune and more thoroughly validate these newly identified molecular subclasses of disease as well as better develop, match, and measure novel therapies according to the specificities and predictors of each of these molecular subtypes”.

“High-throughput genomic technologies and cutting-edge platforms, coupled with big data generated through international consortia of excellence as well as the open sharing of information have tremendously advanced our understanding of the molecular drivers and subtyping of colorectal cancer. Only by collaborating together, across borders, will we succeed in accelerating the translation of molecular subclasses and biomarkers into benefits at patient level, concludes Josep Tabernero, Director of VHIO and co-first author of the review.


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*Guinney J, Dienstmann R, Wang X, de Reyni├Ęs A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21(11):1350-6.

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