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Review

At the Intersection of Cardiology and Oncology: TGFβ as a Clinically Translatable Therapy for TNBC Treatment and as a Major Regulator of Post-Chemotherapy Cardiomyopathy

1
Department of Basic Science, Kansas City University, 1750 Independence Ave, Kansas City, MO 64106, USA
2
Schulich School of Medicine, Western University, London, ON N6A5C1, Canada
3
Children’s Mercy Hospital Kansas City, 2401 Gillham Rd, Kansas City, MO 64108, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Moorthy P. Ponnusamy
Cancers 2022, 14(6), 1577; https://doi.org/10.3390/cancers14061577
Received: 3 February 2022 / Revised: 13 March 2022 / Accepted: 17 March 2022 / Published: 19 March 2022
(This article belongs to the Special Issue Signalling Pathways of Cancer Stem Cells)
Specific/targeted therapies have been shown to be effective in the treatment of certain cancers. Unfortunately, there is currently no targeted therapy for the treatment of triple-negative breast cancer (TNBC), which is why this subtype of breast cancer is associated with poor patient prognosis. While there is an immense focus on the development of new therapies, the issue of cardiotoxicity following chemotherapeutic treatment is commonly overlooked, despite its role as a leading cause of mortality in cancer survivors. This review aims to discuss the connection of TGF-β signaling and its role in modulating cardiac fibrosis and remodeling, as well as its role in TNBC tumor progression, cancer stem cell enrichment, chemoresistance and relapse. Together, we highlight the modulation of TGF-β as a method to target two of the greatest causes of morbidity and mortality in breast cancer patients.
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. While there is immense focus on the development of novel therapies for TNBC treatment, a persistent and critical issue is the rate of heart failure and cardiomyopathy, which is a leading cause of mortality and morbidity amongst cancer survivors. In this review, we highlight mechanisms of post-chemotherapeutic cardiotoxicity exposure, evaluate how this is assessed clinically and highlight the transforming growth factor-beta family (TGF-β) pathway and its significance as a mediator of cardiomyopathy. We also highlight recent findings demonstrating TGF-β inhibition as a potent method to prevent cardiac remodeling, fibrosis and cardiomyopathy. We describe how dysregulation of the TGF-β pathway is associated with negative patient outcomes across 32 types of cancer, including TNBC. We then highlight how TGF-β modulation may be a potent method to target mesenchymal (CD44+/CD24) and epithelial (ALDHhigh) cancer stem cell (CSC) populations in TNBC models. CSCs are associated with tumorigenesis, metastasis, relapse, resistance and diminished patient prognosis; however, due to plasticity and differential regulation, these populations remain difficult to target and continue to present a major barrier to successful therapy. TGF-β inhibition represents an intersection of two fields: cardiology and oncology. Through the inhibition of cardiomyopathy, cardiac damage and heart failure may be prevented, and through CSC targeting, patient prognoses may be improved. Together, both approaches, if successfully implemented, would target the two greatest causes of cancer-related morbidity in patients and potentially lead to a breakthrough therapy. View Full-Text
Keywords: TNBC TGF-β; cardiology; oncology; CSC TNBC TGF-β; cardiology; oncology; CSC
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MDPI and ACS Style

Sulaiman, A.; Chambers, J.; Chilumula, S.C.; Vinod, V.; Kandunuri, R.; McGarry, S.; Kim, S. At the Intersection of Cardiology and Oncology: TGFβ as a Clinically Translatable Therapy for TNBC Treatment and as a Major Regulator of Post-Chemotherapy Cardiomyopathy. Cancers 2022, 14, 1577. https://doi.org/10.3390/cancers14061577

AMA Style

Sulaiman A, Chambers J, Chilumula SC, Vinod V, Kandunuri R, McGarry S, Kim S. At the Intersection of Cardiology and Oncology: TGFβ as a Clinically Translatable Therapy for TNBC Treatment and as a Major Regulator of Post-Chemotherapy Cardiomyopathy. Cancers. 2022; 14(6):1577. https://doi.org/10.3390/cancers14061577

Chicago/Turabian Style

Sulaiman, Andrew, Jason Chambers, Sai C. Chilumula, Vishak Vinod, Rohith Kandunuri, Sarah McGarry, and Sung Kim. 2022. "At the Intersection of Cardiology and Oncology: TGFβ as a Clinically Translatable Therapy for TNBC Treatment and as a Major Regulator of Post-Chemotherapy Cardiomyopathy" Cancers 14, no. 6: 1577. https://doi.org/10.3390/cancers14061577

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