三阴性乳腺癌(TNBC)细胞缺乏雌激素受体(ER),孕激素受体(PRs),和人表皮生长因子受体2(HER2),它(TNBC)占所有乳腺癌的10-15%。TNBC是高度侵入性的,具有更快的生长速度和更高的转移和复发风险。尽管如此,化疗是治疗TNBC的广泛应用选择之一.本研究综述了TNBC亚型的组织学和分子特征,异常表达的信号通路,靶向这些途径的小分子,作为单一药物或与其他治疗剂如化疗剂的组合,免疫治疗,和抗体-药物缀合物;它们的作用机制,挑战,并回顾了未来的前景。使用从SciFinder收集的文献进行了详细的分析审查,PubMed,ScienceDirect,谷歌学者,ACS,Springer,Wiley数据库发现几种小分子抑制剂是治疗TNBC的治疗剂。研究了小分子的作用机制和发挥其作用的不同信号通路,包括临床试验,如果报告。这些小分子抑制剂包括布帕利西,依维莫司,Vandetanib,阿帕替尼,奥拉帕利,红景天苷,等。参与TNBC的一些信号通路,包括VEGF,PARP,STAT3,MAPK,EGFR,P13K,和SRC路径,进行了讨论。由于缺乏这些生物标志物,治疗TNBC的药物开发具有挑战性,化疗是主要的治疗药物。然而,化疗与化疗耐药性和对健康细胞的高毒性有关。因此,对于特异性靶向在TNBC中异常表达的几种信号通路的小分子抑制剂存在持续的需求。我们试图包括该领域的所有最新发展。任何遗漏都是无意的。
Triple-negative breast cancer (TNBC) cells are devoid of estrogen receptors (ERs), progesterone receptor (PRs), and human epidermal growth factor receptor 2 (HER2), and it (TNBC) counts for about 10-15% of all breast cancers. TNBC is highly invasive, having a faster growth rate and a higher risk of metastasis and recurrence. Still, chemotherapy is one of the widely used options for treating TNBC. This study reviewed the histological and molecular characterization of TNBC subtypes, signaling pathways that are aberrantly expressed, and small molecules targeting these pathways, as either single agents or in combination with other therapeutic agents like chemotherapeutics, immunotherapeutics, and antibody-drug conjugates; their mechanisms of action, challenges, and future perspectives were also reviewed. A detailed analytical review was carried out using the literature collected from the SciFinder, PubMed, ScienceDirect, Google Scholar, ACS, Springer, and Wiley databases. Several small molecule inhibitors were found to be therapeutics for treating TNBC. The mechanism of action and the different signaling pathways through which the small molecules exert their effects were studied, including clinical trials, if reported. These small molecule inhibitors include buparlisib, everolimus, vandetanib, apatinib, olaparib, salidroside, etc. Some of the signaling pathways involved in TNBC, including the VEGF, PARP, STAT3, MAPK, EGFR, P13K, and SRC pathways, were discussed. Due to the absence of these biomarkers, drug development for treating TNBC is challenging, with chemotherapy being the main therapeutic agent. However, chemotherapy is associated with chemoresistance and a high toxicity to healthy cells as side effects. Hence, there is a continuous demand for small-molecule inhibitors that specifically target several signaling pathways that are abnormally expressed in TNBC. We attempted to include all the recent developments in this field. Any omission is truly unintentional.