蛋白降解靶向嵌合体技术及其天然产物衍生分子应用于乳腺癌治疗的研究进展

Application and prospect of proteolysis targeting chimeric technology and its natural productderived molecules in breast cancer treatment

摘要:

乳腺癌已成为全球女性发病率最高且发病率呈上升趋势的恶性肿瘤。化疗、内分泌治疗及分子靶向治疗 等传统治疗手段在临床上取得了一定成效，但其耐药性问题严重影响了治疗效果。蛋白降解靶向嵌合体（Proteolysis Targeting Chimeric，PROTAC）技术作为一种新兴的蛋白质降解策略，为治疗耐药性乳腺癌提供了新的可能性，其中天 然产物衍生的PROTAC分子展现出巨大潜力。该文总结了PROTAC技术在乳腺癌治疗中的应用现状、不同分子分型乳 腺癌的关键靶点PROTAC的研究进展，探讨基于天然产物的PROTAC分子设计及其在乳腺癌治疗中的潜在价值及基于 PROTAC技术开发的海洋药物在乳腺癌治疗中的研究前景。

Abstract:

Breast cancer has become the most prevalent malignancy among women globally, with an increasing incidence rate. Traditional treatment modalities such as chemotherapy, endocrine therapy, and molecular targeted therapy have achieved certain clinical successes, but their effectiveness is severely compromised by drug resistance issues. Proteolysis Targeting Chimeric (PROTAC) technology, as an emerging protein degradation strategy, offers new possibilities for treating drug-resistant breast cancer, particularly PROTAC molecules derived from natural products exhibited great potential. This review summarized the current status and future trends of PROTAC technology in breast cancer treatment. It focuses on PROTAC research progress targeting different molecular subtypes of breast cancer, delves into the design of PROTAC molecules based on natural products, and explores their potential value in breast cancer treatment. Additionally, the review provides new insights into the prospects of marine drugs developed based on PROTAC technology in breast cancer treatment.