From molecular Biology to clinical trials. Towards a personalized colorectal cancer terapy

EZEQUIEL LACUNZA

Neuquén

Jornada; X Jornadas FOPA VI Jornadas Oncológicas Hospitalarias; 2016

Abstract: Over the last years, molecular studies through high-throughputtechnologies have led to the confirmation of critical alterations incolorectal cancer (CRC) and the discovery of some new ones, ranging frommutations, DNA-methylations and structural chromosomal changes. Thesegenomic alterations may act in concert to dysregulate specific signalingpathways that normally exert their functions on critical cell phenotypes,including the regulation of cellular metabolism, proliferation,differentiation, and survival. Targeted therapy against key components ofaltered signaling pathways has allowed an improvement in CRC treatment.However, there is a significant percentage of CRC and metastatic CRCpatients that do not benefit from these targeted therapies, thereby beingrestricted to systemic chemotherapy. Mechanisms of resistance have beenassociated with specific gene alterations. To fully understand the natureand significance of the genetic and epigenetic defects in CRC that mayfavor a tumor to evade a given therapy, much work remains to be done.Therefore, a dynamic link between the basic molecular research andpreclinical studies, which ultimately constitute the prelude tostandardized therapies, is very important to have better and effectivetreatments against CRC disease. We present here an updated revision ofthe main molecular features of CRC and their associated therapiescurrently underway in clinical trials. Moreover, we performed anunsupervised classification of CRC clinical trials with the aim ofobtaining an overview of the future perspectives of preclinical studies.