Hypoxia-ROS-HSP Triad Axis in Cancer: Mechanisms, Crosstalk, and Therapeutic Implications.
6 affiliations
- 1Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
- 2Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea.
- 3Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
- 4Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul 02453, Republic of Korea.
- 5Department of Medical Zoology, Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Core Research Institute, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
- 6Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Abstract
Cancer remains one of the leading causes of mortality worldwide, accounting for approximately 20% of all deaths and posing a major threat to global health. Mechanistically, tumorigenesis is driven by complex molecular and cellular mechanisms that enable malignant cells to evade current therapeutic interventions, thereby limiting treatment efficacy and contributing to disease progression. Despite extensive efforts to identify and target key molecular regulators and signaling pathways involved in cancer development, effective and durable treatments remain limited for many cancers, underscoring the need for novel treatment strategies. Consequently, diverse therapeutic strategies are being developed to overcome barriers to treatment response, improve clinical outcomes, and extend patient survival. Among emerging therapeutic targets, HSPs have attracted considerable attention because of their critical roles in maintaining proteostasis, promoting tumor cell survival, and facilitating resistance to therapy. In addition to stress adaptation, oxidative stress and hypoxia are key components of the tumor microenvironment that promote malignant progression through extensive crosstalk with oncogenic signaling pathways. Growing evidence indicates that these pathways are highly interconnected and collectively contribute to cancer metastasis and poor clinical outcomes. In this review, we explore the mechanistic interplay among HSPs, reactive oxygen species (ROS), and hypoxia across various cancers, highlight their potential as integrated therapeutic targets, and explore future strategies to develop more effective anticancer interventions.
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BibTeX
@article{singh2026hypoxiaroshsp,
title = {{Hypoxia-ROS-HSP Triad Axis in Cancer: Mechanisms, Crosstalk, and Therapeutic Implications.}},
author = {Manish Kumar Singh and Hyeong Rok Yun and Jyotsna Ranbhise and Sunhee Han and Seung Geun Yeo and Fu-Shi Quan and Bonglee Kim and Sung Soo Kim and Insug Kang},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15191802},
url = {https://europepmc.org/article/MED/42882502},
note = {CC BY},
}
RIS
TY - JOUR
TI - Hypoxia-ROS-HSP Triad Axis in Cancer: Mechanisms, Crosstalk, and Therapeutic Implications.
AU - Manish Kumar Singh
AU - Hyeong Rok Yun
AU - Jyotsna Ranbhise
AU - Sunhee Han
AU - Seung Geun Yeo
AU - Fu-Shi Quan
AU - Bonglee Kim
AU - Sung Soo Kim
AU - Insug Kang
PY - 2026
DA - 2026/10/02
JO - Cells
DO - 10.3390/cells15191802
UR - https://europepmc.org/article/MED/42882502
AB - Cancer remains one of the leading causes of mortality worldwide, accounting for approximately 20% of all deaths and posing a major threat to global health. Mechanistically, tumorigenesis is driven by complex molecular and cellular mechanisms that enable malignant cells to evade current therapeutic interventions, thereby limiting treatment efficacy and contributing to disease progression. Despite extensive efforts to identify and target key molecular regulators and signaling pathways involved in cancer development, effective and durable treatments remain limited for many cancers, underscoring the need for novel treatment strategies. Consequently, diverse therapeutic strategies are being developed to overcome barriers to treatment response, improve clinical outcomes, and extend patient survival. Among emerging therapeutic targets, HSPs have attracted considerable attention because of their critical roles in maintaining proteostasis, promoting tumor cell survival, and facilitating resistance to therapy. In addition to stress adaptation, oxidative stress and hypoxia are key components of the tumor microenvironment that promote malignant progression through extensive crosstalk with oncogenic signaling pathways. Growing evidence indicates that these pathways are highly interconnected and collectively contribute to cancer metastasis and poor clinical outcomes. In this review, we explore the mechanistic interplay among HSPs, reactive oxygen species (ROS), and hypoxia across various cancers, highlight their potential as integrated therapeutic targets, and explore future strategies to develop more effective anticancer interventions.
SN - 2073-4409
ER -