Dual inhibition of BRAF for cancer treatment: advances and therapeutic potential

BRAF双重抑制在癌症治疗中的应用:进展与治疗潜力

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Abstract

Functioning as a critical regulatory enzyme within the mitogen-activated protein kinase (MAPK) cascade, BRAF kinase orchestrates fundamental biological mechanisms while exhibiting high mutation prevalence in malignant pathologies, including cutaneous melanoma and colorectal adenocarcinoma. While selective BRAF inhibitors show efficacy, their use is hampered by drug resistance and compensatory pathway activation. Dual-target inhibitors, which simultaneously block BRAF and another oncogenic target, offer a promising strategy to enhance therapeutic effects, reduce resistance, and minimize off-target toxicity. These drugs synergistically disrupt compensatory mechanisms, demonstrating robust antitumor activity in preclinical models. This review highlights the structural characteristics and functional roles of BRAF kinase, elucidating its significance in disease pathogenesis and therapeutic targeting. Furthermore, it investigates emerging trends in pharmacological intervention strategies, particularly focusing on the advancement and clinical potential of dual-target therapeutic approaches within the framework of modern drug discovery. Through critical analysis of recent developments, the discussion extends to evaluating challenges and opportunities in designing multi-target agents from a molecular design standpoint.

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