Colorectal cancer in the era of precision medicine

Colorectal cancer is a major public health issue. The incidence of colorectal cancer is increasing in people under the age of 50. The treatment of these cancers is a model in which the integration of medicine targeting molecular alterations in cancer with chemotherapy has led to considerable progress. The treatment of these cancers also represents a challenge for the organisation of care, given the need for patients to have early access to expert centres with medical teams skilled in precision medicine and surgical teams specialising in metastasis surgery. The genomic characterisation of colorectal cancer now makes it possible to consider this disease in terms of the molecular anomalies that characterise its prognosis and predict the effectiveness of the various therapies. The treatment of colorectal cancer has thus entered the era of precision medicine. Twenty percent of localised colorectal cancers and 5% of metastatic disease present a deficit in the repair of DNA mismatches. These cancers are therefore geneti-cally unstable and accumulate a large number of alterations in their genome that are a source of neoantigens. Immunotherapy is now the leading treatment option for these patients. Ten percent of colorectal cancers are associated with the presence of activating mutations in the Braf gene. The presence of a Braf mutation confers a poor prognosis on colorectal cancers. The BRAF proteins produced in the presence of such a mutation are constitutively activated and support the proliferation, invasion and survival of tumour cells. Specific inhibitors (targeted therapies) are currently being used to treat this entity, with better results than chemotherapy. Enzymes in the RAS family can also be activated by specific mutations. Such abnormalities are identified in 40% of colorectal cancers and also underpin cancer progression and a poor progno-sis. Specific inhibitors of activated RAS proteins are currently being developed. In the absence of instability, chemotherapy remains the first-line treatment. Antibodies that neutralise epi-thelial growth factors (in the absence of mutations in the Ras or BRaf genes) or neutralising angiogenesis are used in combination with chemotherapy. Prescribing an treatment for metas-tatic colorectal cancer is a major challenge. It is now possible to obtain significant therapeutic responses in more than 60% of cases when the treatment is appropriate. For some of these patients, medical and surgical teams can proceed to surgery to remove residual metastases, making it possible to cure cancers metastatic cancer.(c) 2023 Published by Elsevier Masson SAS on behalf of l'Acad ' emie nationale de m ' edecine.