Opinion statement
One of the great challenges in digestive oncology is choosing the optimal therapy for RAS-mutated metastatic colorectal cancer (mCRC). Even though the RAS genes and accompanying pathway were identified decades ago and extensive knowledge exists on their role in carcinogenesis, it has proven challenging to translate these insights into new therapies and clinical benefit for patients. However, recently, new drugs targeting this pathway (for example, KRASG12C inhibitors) have shown promising results in clinical trials, as monotherapy or in combination regimens. Although resistance remains an important issue, more knowledge on adaptive resistance and feedback loops in the RAS-pathway has led to strategical combination regimens to overcome this problem. In the past year, many encouraging results have been published or presented at conferences. Even though some of the data is still preliminary, these studies may bring practice-changing results and can lead to a clinical benefit for patients over the coming years. Because of these recent developments, the treatment of RAS-mutated mCRC has become a topic of great interest. Therefore, in this review, we will summarize the standard of care and discuss the most important emerging therapies for this patient population.
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Dr. Janssens, dr. Lambrechts, dr. Geerinckx, dr. Oliveres, dr. Op de Beeck, and dr. Van Camp have nothing to disclose. Dr. Prenen reports personal fees from Amgen, personal fees from Roche, personal fees from Sanofi, personal fees from Astra Zeneca, personal fees from Bayer, outside the submitted work. Dr. Vandamme reports grants and non-financial support from Novartis, grants, personal fees and non-financial support from Ipsen, personal fees from Eisai, personal fees from Roche, personal fees from Bayer, personal fees and non-financial support from Servier, personal fees from Elmedix, outside the submitted work. Dr. Peeters reports other from Amgen, Bayer, Ipsen, Merck, MSD, Qurin, Remedus, Sanofi, Sirtex, Terumo, personal fees from Amgen, Bayer, BMS, Merck, MSD, Roche, Sanofi, Servier, Sirtex, grants from Amgen (Inst.), Bayer (Inst.), BMS (Inst.), Ipsen (Inst.), Novartis (Inst.), Roche (Inst.), outside the submitted work.
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Janssens, K., Lambrechts, C., Geerinckx, B. et al. New Developments in Treating RAS-Mutated Metastatic Colorectal Cancer. Curr. Treat. Options in Oncol. 24, 965–987 (2023). https://doi.org/10.1007/s11864-023-01095-y
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DOI: https://doi.org/10.1007/s11864-023-01095-y