School of Science, STEM College, RMIT University, Melbourne, VIC 3001, Australia.
Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia.
Int J Mol Sci. 2021 Sep 8;22(18):9722. doi: 10.3390/ijms22189722.
Targeted chemotherapy has become the forefront for cancer treatment in recent years. The selective and specific features allow more effective treatment with reduced side effects. Most targeted therapies, which include small molecules, act on specific molecular targets that are altered in tumour cells, mainly in cancers such as breast, lung, colorectal, lymphoma and leukaemia. With the recent exponential progress in drug development, programmed cell death, which includes apoptosis and autophagy, has become a promising therapeutic target. The research in identifying effective small molecules that target compensatory mechanisms in tumour cells alleviates the emergence of drug resistance. Due to the heterogenous nature of breast cancer, various attempts were made to overcome chemoresistance. Amongst breast cancers, triple negative breast cancer (TNBC) is of particular interest due to its heterogeneous nature in response to chemotherapy. TNBC represents approximately 15% of all breast tumours, however, and still has a poor prognosis. Unlike other breast tumours, signature targets lack for TNBCs, causing high morbidity and mortality. This review highlights several small molecules with promising preclinical data that target autophagy and apoptosis to induce cell death in TNBC cells.
近年来，靶向化疗已成为癌症治疗的前沿。其选择性和特异性的特点使得治疗更加有效，副作用更小。大多数靶向治疗药物包括小分子，作用于肿瘤细胞中改变的特定分子靶点，主要是在乳腺癌、肺癌、结直肠癌、淋巴瘤和白血病等癌症中。随着药物开发的最近呈指数级增长，程序性细胞死亡，包括细胞凋亡和自噬，已成为一个有前途的治疗靶点。研究确定针对肿瘤细胞补偿机制的有效小分子药物可以缓解耐药性的出现。由于乳腺癌的异质性，人们进行了各种尝试来克服化疗耐药性。在乳腺癌中，三阴性乳腺癌（TNBC）因其对化疗的异质性反应而特别引人关注。然而，TNBC 约占所有乳腺癌肿瘤的 15%，但其预后仍然较差。与其他乳腺癌不同，TNBC 缺乏特征性靶点，导致发病率和死亡率高。这篇综述强调了几种具有有前途的临床前数据的小分子药物，这些药物通过靶向自噬和细胞凋亡来诱导 TNBC 细胞死亡。
