Ion Channel Biology Lab, Department of Biotechnology, Indian Institute of Technology Hyderabad (IITH), Kandi, Telangana, 502285, India.
Breast Cancer Res Treat. 2019 Jan;173(1):11-21. doi: 10.1007/s10549-018-4970-0. Epub 2018 Sep 21.
The purpose of this review article is to discuss the potential of T-type voltage gated calcium channels (VGCCs) as drug targets in breast cancer. Breast cancer, attributable to the different molecular subtypes, has a crucial need for therapeutic strategies to counter the mortality rate. VGCCs play an important role in regulating cytosolic free calcium levels which regulate cellular processes like tumorigenesis and cancer progression. In the last decade, T-type VGCCs have been investigated in breast cancer proliferation. Calcium channel blockers, in general, have shown an anti-proliferative and cytotoxic effects. T-type VGCC antagonists have shown growth inhibition owing to the inhibition of Ca3.2 isoform. Ca3.1 isoform has been indicated as a tumour-suppressor gene candidate and is reported to support anti-proliferative and apoptotic activity in breast cancer. The distribution of T-type VGCC isoforms in different breast cancer molecular subtypes is diverse and needs to be further investigated. The role of T-type VGCCs in breast cancer migration, metastasis and more importantly in epithelial to mesenchymal transition (EMT) is yet to be elucidated. In addition, interlaced therapy, using a combination of chemotherapy drugs and T-type VGCC blockers, presents a promising therapeutic approach for breast cancer but more validation and clinical trials are needed. Also, for investigating the potential of T-type VGCC blocker therapy, there is a need for isoform-specific agonists/antagonists to define and discover roles of T-type VGCC specific isoforms.
Our article provides a review of the role of T-type VGCCs in breast cancer and also discusses future of the research in this area so that it can be ascertained whether there is any potential of T-type VGCCs as drug targets in breast cancer.
本文旨在探讨 T 型电压门控钙通道（VGCC）作为乳腺癌药物靶点的潜力。乳腺癌因分子亚型不同，急需寻找新的治疗策略来降低死亡率。VGCC 在调节细胞内游离钙水平方面发挥着重要作用，而钙水平的变化又调控着肿瘤发生和癌症进展等细胞过程。在过去十年中，T 型 VGCC 已被用于研究乳腺癌增殖。一般来说，钙通道阻滞剂表现出抗增殖和细胞毒性作用。T 型 VGCC 拮抗剂通过抑制 Ca3.2 同工型显示出生长抑制作用。Ca3.1 同工型已被认为是候选肿瘤抑制基因，并被报道在乳腺癌中支持抗增殖和促凋亡活性。不同乳腺癌分子亚型中 T 型 VGCC 同工型的分布存在差异，需要进一步研究。T 型 VGCC 在乳腺癌迁移、转移，更重要的是在上皮间质转化（EMT）中的作用尚待阐明。此外，联合化疗药物和 T 型 VGCC 阻滞剂的交错治疗为乳腺癌提供了一种很有前途的治疗方法，但需要更多的验证和临床试验。此外，为了研究 T 型 VGCC 阻滞剂治疗的潜力，需要使用同工型特异性激动剂/拮抗剂来定义和发现 T 型 VGCC 特定同工型的作用。
本文综述了 T 型 VGCC 在乳腺癌中的作用，并讨论了该领域未来的研究方向，以确定 T 型 VGCC 是否有可能成为乳腺癌的药物靶点。
