Oncotarget

Reviews:

Signaling pathway dysregulation in breast cancer

Dinara Ryspayeva _, Attila A. Seyhan, William J. MacDonald, Connor Purcell, Tyler J. Roady, Maryam Ghandali, Nataliia Verovkina, Wafik S. El-Deiry, Martin S. Taylor and Stephanie L. Graff

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Oncotarget. 2025; 16:168-201. https://doi.org/10.18632/oncotarget.28701

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Abstract

Dinara Ryspayeva1,2,3,4, Attila A. Seyhan1,2,3,4,5, William J. MacDonald1,2,3,4, Connor Purcell1,2,3,4, Tyler J. Roady1,2,3,4,5, Maryam Ghandali1,2,3,4, Nataliia Verovkina1,2,3,4, Wafik S. El-Deiry1,2,3,4,5,7, Martin S. Taylor2,3,4,5,6 and Stephanie L. Graff4,7

1 Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, RI 02903, USA

2 Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, RI 02903, USA

3 Joint Program in Cancer Biology, Lifespan Health System and Brown University, RI 02903, USA

4 Legorreta Cancer Center at Brown University, RI 02903, USA

5 Pathobiology Graduate Program, Brown University, RI 02903, USA

6 Brown Center on the Biology of Aging, Brown University, RI 02903, USA

7 Department of Medicine, Hematology/Oncology Division, Lifespan Health System and Brown University, RI 02903, USA

Correspondence to:

Dinara Ryspayeva, email: [email protected]

Keywords: breast cancer; oncogenic pathways; signal dysregulation in cancer; therapeutic approaches; clinical trials

Received: December 20, 2024     Accepted: March 03, 2025     Published: March 13, 2025

Copyright: © 2025 Ryspayeva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

This article provides a comprehensive analysis of the signaling pathways implicated in breast cancer (BC), the most prevalent malignancy among women and a leading cause of cancer-related mortality globally. Special emphasis is placed on the structural dynamics of protein complexes that are integral to the regulation of these signaling cascades. Dysregulation of cellular signaling is a fundamental aspect of BC pathophysiology, with both upstream and downstream signaling cascade activation contributing to cellular process aberrations that not only drive tumor growth, but also contribute to resistance against current treatments. The review explores alterations within these pathways across different BC subtypes and highlights potential therapeutic strategies targeting these pathways. Additionally, the influence of specific mutations on therapeutic decision-making is examined, underscoring their relevance to particular BC subtypes. The article also discusses both approved therapeutic modalities and ongoing clinical trials targeting disrupted signaling pathways. However, further investigation is necessary to fully elucidate the underlying mechanisms and optimize personalized treatment approaches.


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