Small molecule agents for triple negative breast cancer: Current status and future prospects

• Published in: Translational oncology Vol. 41; p. 101893
• Main Authors: Ou, Yan, Wang, Mengchao, Xu, Qian, Sun, Binxu, Jia, Yingjie
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2024; Neoplasia Press; Elsevier
• Subjects: Review; Small molecule drugs; Targeted therapies; Triple-negative breast cancer; Targeted therapies; Small molecule drugs; Triple-negative breast cancer
• ISSN: 1936-5233; 1936-5233
• DOI: 10.1016/j.tranon.2024.101893

•A comprehensive summary of small molecule drugs targeting TNBC.•Clinical trial progress, resistance mechanisms and solutions for each of the small molecule drugs for TNBC are listed by target.•No previous articles have listed every small molecule drug for triple negative breast cancer by target.•Offers other new ideas for treating TNBC. Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis. The number of cases increased by 2.26 million in 2020, making it the most commonly diagnosed cancer type in the world. TNBCs lack hormone receptor (HR) and human epidermal growth factor 2 (HER2), which limits treatment options. Currently, paclitaxel-based drugs combined with other chemotherapeutics remain the main treatment for TNBC. There is currently no consensus on the best therapeutic regimen for TNBC. However, there have been successful clinical trials exploring large-molecule monoclonal antibodies, small-molecule targeted drugs, and novel antibody-drug conjugate (ADC). Although monoclonal antibodies have produced clinical success, their large molecular weight can limit therapeutic benefits. It is worth noting that in the past 30 years, the FDA has approved small molecule drugs for HER2-positive breast cancers. The lack of effective targets and the occurrence of drug resistance pose significant challenges in the treatment of TNBC. To improve the prognosis of TNBC, it is crucial to search for effective targets and to overcome drug resistance. This review examines the clinical efficacy, adverse effects, resistance mechanisms, and potential solutions of targeted small molecule drugs in both monotherapies and combination therapies. New therapeutic targets, including nuclear export protein 1 (XPO1) and hedgehog (Hh), are emerging as potential options for researchers and become integrated into clinical trials for TNBC. Additionally, there is growing interest in the potential of targeted protein degradation chimeras (PROTACs), degraders of rogue proteins, as a future therapy direction. This review provides potentially valuable insights with clinical implications. [Display omitted]