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Colorectal cancer (CRC) is among the most prevalent malignancies globally, and advancements in molecular oncology have demonstrated that genetic alterations significantly influence its behaviour and therapeutic responses. KRAS, NRAS, and BRAF mutations are very relevant since they have a direct effect on treatment plans, prognosis, and whether or not a person can access targeted therapy.

Mutations in KRAS and NRAS

They make proteins that control the RAS-MAPK signalling pathway, which regulates how cells grow and divide. Changes in these genes, which are most often seen in exons 2, 3, and 4, keep the pathway active all the time, which causes cancer cells to grow out of control. KRAS mutations affect about 40–50% of individuals with metastatic CRC, while NRAS mutations affect about 3–5%. These changes are signs that a person is resistant to anti-EGFR monoclonal antibodies like cetuximab and panitumumab. Their presence means that it is important to test for them before starting these types of treatments.
Mutations in BRAF

This mutation is linked to aggressive tumour biology, rapid growth, and a lower chance of survival than other subtypes. BRAF V600E mutations are different from KRAS/NRAS mutations in that they can also be used to predict adverse outcomes.
Effect on Treatment

Instead, chemotherapy regimens like FOLFOX or FOLFIRI are used, often with VEGF inhibitors like bevacizumab. Studies have demonstrated enhanced results in BRAF V600E-mutated cases with combination treatments that include a BRAF inhibitor (e.g., encorafenib), a MEK inhibitor (e.g., binimetinib), and an EGFR inhibitor.
Testing molecules and precision oncology

Finding out the mutation status of KRAS, NRAS, and BRAF is now a common part of the workup for metastatic CRC. Next-generation sequencing (NGS) or PCR-based technologies can be used to undertake molecular testing. Oncologists can make a personalised treatment plan by identifying these mutations early. This helps them avoid medications that don't work and focus on therapies that are most likely to work.

Prognosis and Research Directions

Patients with KRAS or NRAS mutations typically have a prognosis comparable to that of wild-type patients, contingent upon the selection of suitable targeted therapy. However, BRAF-mutated CRC often has a worse prognosis, which shows how important it is to try new treatments and participate in clinical trials. Current research is investigating combinations of immunotherapy, sequences of targeted therapy, and new medicines to surmount resistance mechanisms.
Conclusion
KRAS, NRAS, and BRAF mutations are important biomarkers in colorectal cancer that help doctors decide which targeted medicines to use and how to treat the disease as a whole. All advanced CRC patients should undergo comprehensive molecular profiling to guarantee appropriate, individualised therapy, resulting in enhanced survival rates and an improved quality of life.