Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Clinically Translatable Approaches of Inhibiting TGF-β to Target Cancer Stem Cells in TNBC

Version 1 : Received: 1 September 2021 / Approved: 2 September 2021 / Online: 2 September 2021 (15:58:45 CEST)
Version 2 : Received: 8 September 2021 / Approved: 8 September 2021 / Online: 8 September 2021 (20:53:29 CEST)

A peer-reviewed article of this Preprint also exists.

Sulaiman, A.; McGarry, S.; Chilumula, S.C.; Kandunuri, R.; Vinod, V. Clinically Translatable Approaches of Inhibiting TGF-β to Target Cancer Stem Cells in TNBC. Biomedicines 2021, 9, 1386. Sulaiman, A.; McGarry, S.; Chilumula, S.C.; Kandunuri, R.; Vinod, V. Clinically Translatable Approaches of Inhibiting TGF-β to Target Cancer Stem Cells in TNBC. Biomedicines 2021, 9, 1386.

Journal reference: Biomedicines 2021, 9, 1386
DOI: 10.3390/biomedicines9101386

Abstract

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. In this review, we highlight the complexity of the transforming growth factor-beta family (TGF-β) pathway and discuss how the dysregulation of the TGF-β pathway promotes oncogenic attributes in TNBC which negatively affects patient prognosis. Moreover, we discuss recent findings highlighting TGF-β inhibition as a potent method to target mesenchymal (CD44+/CD24-) and epithelial (ALDHhigh) cancer stem cell (CSC) populations. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to differential signal pathway enrichment and plasticity, these popula-tions remain difficult to target and persist as a major barrier barring successful therapy. This review highlights the importance of TGF-β as a driver of chemoresistance, radioresistance and reduced patient prognosis in breast cancer and discusses novel treatment strategies which modulate TGF-β, impede cancer progression and reduce the rate of resistance generation via targeting the CSC populations in TNBC and thus reducing tumorigenicity. Potential TGF-β inhibitors targeting based on clinical trials are summarized for further investigation which may lead to the development of novel therapies to improve TNBC patient prognosis.

Keywords

Triple Negative Breast Cancer; Cancer Stem Cell; TGF-β

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