Liao Minru, Zhang Jin, Wang Guan, Wang Leiming, Liu Jie, Ouyang Liang, Liu Bo
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
The Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518107, China.
J Med Chem. 2021 Mar 11;64(5):2382-2418. doi: 10.1021/acs.jmedchem.0c01180. Epub 2021 Mar 2.
Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, but an effective targeted therapy has not been well-established so far. Considering the lack of effective targets, where do we go next in the current TNBC drug development? A promising intervention for TNBC might lie in small-molecule drugs that precisely target different molecular characteristics of TNBC. However, an ideal single-target drug discovery still faces a huge challenge. Alternatively, other new emerging strategies, such as dual-target drug, drug repurposing, and combination strategies, may provide new insight into the improvement of TNBC therapeutics. In this review, we focus on summarizing the current situation of a series of candidate small-molecule drugs in TNBC therapy, including single-target drugs, dual-target drugs, as well as drug repurposing and combination strategies that will together shed new light on the future directions targeting TNBC vulnerabilities with small-molecule drugs for future therapeutic purposes.
三阴性乳腺癌(TNBC)是最具侵袭性的乳腺癌亚型,但迄今为止尚未建立有效的靶向治疗方法。考虑到缺乏有效的靶点,在当前三阴性乳腺癌药物研发中我们接下来该何去何从?三阴性乳腺癌的一种有前景的干预措施可能在于精确靶向三阴性乳腺癌不同分子特征的小分子药物。然而,理想的单靶点药物发现仍面临巨大挑战。另外,其他新兴策略,如双靶点药物、药物再利用和联合策略,可能为改善三阴性乳腺癌治疗提供新的思路。在本综述中,我们着重总结了一系列候选小分子药物在三阴性乳腺癌治疗中的现状,包括单靶点药物、双靶点药物以及药物再利用和联合策略,这些将共同为未来以小分子药物靶向三阴性乳腺癌弱点的治疗目的指明新的方向。