Mir Manzoor A, Qayoom Hina, Mehraj Umar, Nisar Safura, Bhat Basharat, Wani Nissar A
Department of Bioresources, School of Biological Sciences, University of Kashmir, Srinagar, India.
Curr Cancer Drug Targets. 2020;20(8):586-602. doi: 10.2174/1570163817666200518081955.
Triple negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer accounting for 15-20% of cases and is defined by the lack of hormonal receptors viz., estrogen receptor (ER), progesterone receptor (PR) and expression of human epidermal growth receptor 2 (HER2). Treatment of TNBC is more challenging than other subtypes of breast cancer due to the lack of markers for the molecularly targeted therapies (ER, PR, and HER-2/ Neu), the conventional chemotherapeutic agents are still the mainstay of the therapeutic protocols of its patients. Despite, TNBC being more chemo-responsive than other subtypes, unfortunately, the initial good response to the chemotherapy eventually turns into a refractory drug-resistance. Using a monotherapy for the treatment of cancer, especially high-grade tumors like TNBC, is mostly worthless due to the inherent genetic instability of tumor cells to develop intrinsic and acquired resistance. Thus, a cocktail of two or more drugs with different mechanisms of action is more effective and could successfully control the disease. Furthermore, combination therapy reveals more, or at least the same, effectiveness with lower doses of every single agent and decreases the likelihood of chemoresistance. Herein, we shed light on the novel combinatorial approaches targeting PARP, EGFR, PI3K pathway, AR, and wnt signaling, HDAC, MEK pathway for efficient treatment of high-grade tumors like TNBC and decreasing the onset of resistance.
三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌亚型之一，占病例的15%-20%，其定义为缺乏激素受体，即雌激素受体（ER）、孕激素受体（PR）以及人表皮生长受体2（HER2）的表达。由于缺乏分子靶向治疗的标志物（ER、PR和HER-2/Neu），TNBC的治疗比其他乳腺癌亚型更具挑战性，传统化疗药物仍然是其患者治疗方案的主要支柱。尽管TNBC比其他亚型对化疗更敏感，但不幸的是，最初对化疗的良好反应最终会转变为难治性耐药。使用单一疗法治疗癌症，尤其是像TNBC这样的高级别肿瘤，由于肿瘤细胞固有的基因不稳定性会产生内在和获得性耐药，大多是没有价值的。因此，两种或更多种具有不同作用机制的药物联合使用更有效，并且可以成功控制疾病。此外，联合治疗显示出更高的疗效，或者至少与单一药物低剂量使用时相同，并且降低了化疗耐药的可能性。在此，我们阐述了针对PARP、EGFR、PI3K通路、AR和wnt信号通路、HDAC、MEK通路的新型联合治疗方法，以有效治疗像TNBC这样的高级别肿瘤并减少耐药的发生。
