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Dr. Sewanti Limaye

Although colorectal cancer remains a prominent cause of mortality, the last few decades have seen a significant improvement in the overall survival rates. This is, in part, due to enhanced screening measures, early diagnosis, and aggressive surgical techniques. The progress made in understanding active cancer pathways and developing novel therapeutic options have also helped.

Prevention of colorectal cancer with diets, supplements, preventive medications such as aspirin, and early methods of detection such as screening blood tests and stool tests is being studied. In the early stages, the disease is mostly treated with surgical resection. Genomic tests are being developed to predict the specific risk of recurrence and prognosis for patients.

Combining chemotherapy with targeted therapy helps improve outcomes in advanced stages, and pathway analysis is critical to planning treatment. Mutations in KRAS, APC, TP53 and extended RAS panels are some of the commonly studied alterations. The Cancer Genome Atlas Network and other research teams have identified newer set of genes that could be mutated in colorectal cancer, thereby contribute to treatment resistance. They could also serve as potential targets for therapy and drug development such as BRAF PIK3CA, ERBB2, PTEN, IGF2 mutations and TRK fusions.

Approximately 5% of advanced colorectal cancers are found to be MSI –H, which is the biological footprint of mismatch repair deficiency (dMMR). These cells are more visible to the immune system and have shown excellent response to immunotherapy with PD-L1 inhibitors alone or a combination of PD-L1 inhibitor with CTLA-4 antibody.

Targeted therapies and immunotherapy are personalized treatment options for colorectal cancer. More research is underway to enable novel therapies and combinations and brings hope of improved survival for patients.

This article has been written by Dr. Sewanti Limaye, MBBS, MD (USA), MS (USA), Consultant, Medical Oncology, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, and Ex-Consultant Medical Oncology, Dana Farber Cancer Institute, Harvard Med School and Columbia University Medical Center, US.