Artificial intelligence and compUtational biology for pRedicting nOvel immunotheRApeutic strategies in microsatellite stability colon cancer patients - AURORA

Colorectal cancer (CRC) is among the types of cancer that, in recent years, have shown the most significant improvements in survival rates — thanks to prevention, as well as to innovative surgical techniques and new drugs. Among these, immunotherapy has certainly played an important role. However, this type of treatment is effective only in a specific subgroup of tumors — those characterized by microsatellite instability (MSI). To date, there are no highly specific biomarkers to predict the response to immunotherapy; rather, indicators such as PD-L1 expression and microsatellite status (MS) are used.

The AURORA project aims to improve the stratification of CRC patients by analyzing microsatellite status as a continuous variable. The goal is to develop an algorithm capable of predicting the response to immunotherapy in patients who, although classified as microsatellite stable (MSS), present sufficient MSI areas compared to MSS to hypothesize a response to anti-PD1 treatment when administered in combination with a “repurposed” drug — that is, a drug already used in the past for other purposes — which can influence DNA repair systems by inducing an MSI state.

This ambitious project could lead to an increase in the proportion of CRC patients who benefit from immunotherapy, significantly raising the current percentage of responsive patients, which stands at 15% of cases. In an effort to identify experimental solutions that can accelerate the transfer of knowledge gained from the project into clinical practice, the models developed within AURORA will be used to test the repurposed drugs — a strategy that has already proven successful in other fields, since these drugs are well known in clinical settings. Ultimately, the AURORA project could offer new therapeutic opportunities for colorectal cancer patients, with potential economic benefits for the healthcare system.