The past, present, and future treatment of BRAF V600‑mutant metastatic colorectal cancer: A comprehensive review
Combination therapy with BRAF inhibitors, EGFR inhibitors, and sometimes MEK inhibitors is now the standard of care for BRAF V600‑mutant metastatic colorectal cancer and is being tested as first‑line treatment.
BRAF V600‑mutant metastatic colorectal cancer comprises a biologically distinct and clinically aggressive subset of metastatic colorectal cancer. Early attempts to apply single‑agent BRAF V600 inhibition failed because of rapid acquired resistance and reactivation of mitogen‑activated protein kinase signaling. Over the last decade, rational combinations (BRAF inhibitors and epidermal growth factor receptor inhibitors with or without mitogen‑activated protein kinase kinase inhibitors) have become the standard of care in the refractory setting and are now being evaluated upfront, whereas a wave of next‑generation approaches (extracellular signal‑regulated kinase and SHP2 inhibitors, receptor tyrosine kinase‑targeted agents, and immunotherapy combinations) aims to prevent or overcome resistance.
Understanding and overcoming resistance to BRAF‑targeted therapy is critical for improving outcomes in patients with this aggressive subset of metastatic colorectal cancer.
Evidence level: Klinikai vizsgálat. Formális klinikai vizsgálati eredmény.
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