28IN - New molecular classification of colorectal cancer

Date 28 September 2014
Event ESMO 2014
Session Advances in precision medicine of metastatic colorectal cancer
Topics Colon Cancer
Rectal Cancer
Pathology/Molecular Biology
Presenter Krisztian Homicsko
Citation Annals of Oncology (2014) 25 (suppl_4): iv12-iv13. 10.1093/annonc/mdu296
Authors K. Homicsko
  • -, Centre Multidisciplinaire d'Oncologie-CePo, - - Lausanne/CH

Abstract

Body

Abstract:

Colorectal cancer (CRC) is a heterogeneous disease, and currently only Ras mutation status is available to predict treatment responses for a small fraction of CRC patient populations who are treated with the epidermal growth factor receptor–targeted drug, cetuximab. Hence, it is necessary to develop biomarkers that stratify CRC patients into different subtypes based on the distinctive tumor biology in subsets of patient samples such that personalized/precise treatment strategies using various drugs can be designed. Cancer subtypes are well established in breast cancer, however, it is in its infancy in gastrointestinal tumors. Our classification of pancreatic ductal adenocarcinomas (Nat Med. 2011 Apr;17 (4):500-3) with distinct drug sensitivity and prognosis paved the way to the identification of colorectal cancer subtypes. We have shown (Nat Med. 2013 May;19(5):619-25) that CRC, both primary and metastatic tumors, can be subdivided into five distinct subtypes using gene expression profiles from 1,290 CRC tumors and consensus-based unsupervised clustering. One of the resulting subtypes was subdivided into two sub-subtypes based on their bimodal response to the cetuximab treatment using 80 patient samples. Interestingly, Filamin-A expression delineates one of the sub-subtypes and predicts resistance to cetuximab and sensitivity to Met tyrosine kinase receptor inhibitors. Overall, we identified six clinically relevant CRC subtypes with distinct cellular phenotypes and signaling mechanisms. Moreover, these subtypes show different disease-free prognoses after initial surgical resection with three subtypes showing better prognosis. On the other hand, the other two subtypes with poor and intermediate disease free survival are associated with sensitivity to the FOLFIRI chemotherapy regimen. Together these data strongly support that patients with CRC should be stratified according to tumor subtypes, however, further studies are required to validate our suggested subtype specific personalized therapeutic options.

Disclosure:

All authors have declared no conflicts of interest.