Small molecule Mcl-1 inhibitor for triple negative breast cancer therapy

Front Cell Dev Biol. 2024 Sep 20:12:1408107. doi: 10.3389/fcell.2024.1408107. eCollection 2024.

Abstract

Apoptosis is an evolutionarily conserved cell death pathway that plays a crucial role in maintaining tissue homeostasis, orchestrating organismal development, and eliminating damaged cells. Dysregulation of apoptosis can contribute to the pathogenesis of malignant tumors and neurodegenerative diseases. Anticancer drugs typically possess the capacity to induce apoptosis in tumor cells. The Bcl-2 protein family, consisting of 27 members in humans, serves as the key regulator of mitochondrial function. This family can be divided into two functional groups: anti-apoptotic proteins (e.g., Bcl-2, Bcl-xl, Mcl-1) and pro-apoptotic proteins (e.g., Bad, Bax). Mcl-1 exerts its function by binding pro-apoptotic Bcl-2 proteins thereby preventing apoptosis induction. Overexpression of Mcl-1 not only correlates closely with tumorigenesis but also associates significantly with resistance towards targeted therapy and conventional chemotherapy. Effective induction of apoptosis can be achieved through inhibition or interference with Mcl-1. Thus, this mini review discusses existing Mcl-1 inhibitors.

Keywords: apoptosis; cancer; drug; inhibitor; therapy.

Publication types

  • Review

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by HSCNO-2019-LIFT-002 from LSU Leveraging Innovation for Technology Transfer (LIFT2) Grant. Our research is also supported by grants Nos 2023R5247 and 2024C03010, Zhejiang Provincial Department of Science and Technology.