Recent technological advances have provided powerful insights into the molecular determinants of human tumours. In many cases, tumour regression has been the result of blocking a single mutant protein responsible for both the initiation and maintenance of the cancer, called an oncogenic driver mutation. Often oncogenic driver mutations are found in the very genes responsible for the production of the proteins that maintain normal cell growth, division and survival.
However, many new, important technological advances have not been translated into effective treatments very quickly. This is due to the difficulty in predicting how the complex mutational background and the adaptive resilience of cancer cells influence the activity of the main oncogene and modify the response to therapies. Sophisticated models of the disease and specialist research teams can quicken this process.
The Translational Cancer Medicine unit of the Instituto di Candiolo (University of Turin School of Medicine) explores the mechanisms of tumour dependency on oncogenic drivers and how this dependency is affected by genomic or functional modifiers, with an emphasis on colorectal cancer (CRC).
UNITO’s experimental pipeline interrogates multi-dimensional data for discovery and hypothesis validation then follows on with cell-based mechanistic investigations and preclinical validation in patient-derived organoids, or tumouroids. Tumouroids are models of cancer created from fragments of human tumour tissue or suspensions of disassociated tumour cells cultured in a gel-like three-dimensional environment. These models are used to test the efficacy of anti-tumour molecules and therapies in a living organism. Through this approach, the Translational Cancer Medicine unit has made significant contributions to the finding that the hyperactivation of many treatment-responding oncogenic products correlates with resistance to cetuximab and panitumumab (two anti-EGFR cancer treatments). Pharmacologic inhibition of such resistance mechanisms re-sensitises cancer cells to anti-EGFR therapy, thus broadening therapeutic options for people with colorectal cancer. Livio Trusolino, M.D. PhD, Professor at the University of Torino Medical School: “Our studies provide a systematic functional approach to evaluate response to targeted therapies in human cancers, highlight new mechanisms of responsiveness to anti-EGFR therapies, and provide a new vocabulary for the molecular management of colorectal cancer with immediate clinical implications.” In COLOSSUS the team at UNITO are bringing their expertise to bear testing novel combinatorial treatment strategies for MSS RAS mt mCRC COLOSSUS subtypes.
Livio Trusolino, M.D. PhD, Professor at the University of Torino Medical School: “Our studies provide a systematic functional approach to evaluate response to targeted therapies in human cancers, highlight new mechanisms of responsiveness to anti-EGFR therapies, and provide a new vocabulary for the molecular management of colorectal cancer with immediate clinical implications.”
In COLOSSUS the team at UNITO are bringing their expertise to bear testing novel combinatorial treatment strategies for MSS RAS mt mCRC COLOSSUS subtypes.