Erkan Topkan¹, Doga Topkan², Efsun Somay³* and Ugur Selek⁴

¹Department of Radiation Oncology, Faculty of Medicine, Baskent University, Adana, Turkey ²Department of Clinical Pharmacy, Faculty of Pharmacy, Marmara University, Istanbul, Turkey ³Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Baskent University, Ankara, Turkey ⁴Department of Radiation Oncology, School of Medicine, Koc University, Istanbul, Turkey

*Corresponding Author: Efsun Somay, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Baskent University, Ankara, Turkey.

Received: October 27, 2025; Published: October 31, 2025

Abstract

Head and neck cancers (HNCs) constitute a heterogeneous group of malignancies with persistently poor survival outcomes despite significant advances in surgery, radiotherapy, and systemic therapy. Therapeutic resistance—both intrinsic and acquired—remains the principal barrier to cure. Mounting evidence implicates Heat Shock Protein 27 (HSP27), a small molecular chaperone encoded by HSPB1, as a critical mediator of resistance across multiple treatment modalities. HSP27 regulates essential cellular processes, including protein folding, apoptosis inhibition, DNA repair, redox homeostasis, and cytoskeletal stabilization, thereby enabling tumor cells to endure cytotoxic stress. Elevated expression and phosphorylation of HSP27 have been consistently associated with poor responses to chemoradiotherapy, enhanced metastatic potential, and inferior survival in patients with HNC. Furthermore, recent studies highlight its emerging role in resistance to targeted therapies and immunotherapy through stabilization of PI3K/AKT and MAPK signaling pathways and modulation of the immune microenvironment. Accordingly, this review aims to synthesize mechanistic, preclinical, and clinical evidence delineating the multifaceted role of HSP27 in HNC pathobiology and treatment resistance. By integrating data across molecular, translational, and therapeutic domains, it aims to elucidate how HSP27 contributes to radio-, chemo-, and immune resistance; evaluate its potential as a prognostic and predictive biomarker; and outline emerging strategies for therapeutic targeting. A deeper understanding of HSP27’s central role in adaptive stress responses may inform biomarker-guided and combinatorial approaches to overcome resistance and improve outcomes in patients with head and neck cancers.

Keywords: Head and Neck Cancer; Heat Shock Protein 27; Treatment Resistance; Radiotherapy; Systemic Therapies

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Citation

Citation: Efsun Somay., et al. “Heat Shock Protein 27 as a Driver of Resistance to Radiotherapy and Systemic Therapies in Head and Neck Cancers: From Mechanisms to Therapeutic Targeting".Acta Scientific Cancer Biology 9.5 (2025): 03-10.

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