Unleashing the Power of Yes-Associated Protein in Ferroptosis and Drug Resistance in Breast Cancer, with a Special Focus on Therapeutic Strategies

Author:

Malla RamaRao1ORCID,Kundrapu Durga Bhavani1,Bhamidipati Priyamvada1,Nagaraju Ganji Purnachandra2ORCID,Muniraj Nethaji3ORCID

Affiliation:

1. Cancer Biology Laboratory, Department of Biochemistry and Bioinformatics, GITAM School of Science, GITAM (Deemed to be University), Visakhapatnam 530045, Andhra Pradesh, India

2. Department of Hematology and Oncology, Heersink School of Medicine, University of Alabama, Birmingham, AL 35233, USA

3. Center for Cancer and Immunology Research, Children’s National Hospital, 111 Michigan Avenue NW, Washington, DC 20010, USA

Abstract

The YAP protein is a critical oncogenic mediator within the Hippo signaling pathway and has been implicated in various cancer types. In breast cancer, it frequently becomes activated, thereby contributing to developing drug-resistance mechanisms. Recent studies have underscored the intricate interplay between YAP and ferroptosis within the breast tumor microenvironment. YAP exerts a negative regulatory effect on ferroptosis, promoting cancer cell survival and drug resistance. This review offers a concise summary of the current understanding surrounding the interplay between the YAP pathway, ferroptosis, and drug-resistance mechanisms in both bulk tumor cells and cancer stem cells. We also explore the potential of natural compounds alone or in combination with anticancer therapies for targeting the YAP pathway in treating drug-resistant breast cancer. This approach holds the promise of enhancing the effectiveness of current treatments and paving the way for developing novel therapeutics.

Funder

GITAM

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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