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January 16, 2026Cancers5 citationsOpen Access

Stress Granule-Driven Resistance in Cancer: Mechanisms and Emerging Strategies

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ARAbirami RajendiranGRGanesh RamakrishnanTOTakbum Ohn

Key Points

  • The central aim is to explore the role of stress granules in cancer therapy resistance and emerging strategies to target them.
  • Review of existing literature on stress granule formation and function in cancer cells.
  • Analysis of chemotherapeutic agents and their effects on stress granule kinetics.
  • Discussion of oncogenic signaling pathways that influence stress granule dynamics.
  • Stress granules enable cancer cells to avoid apoptosis and adapt to therapeutic stress.
  • Chemotherapeutic agents and tumor microenvironment stressors significantly promote stress granule formation.
  • Targeting stress granules with kinase inhibitors demonstrates potential in addressing therapy resistance.

Abstract

Stress granules (SGs) are dynamic, membraneless organelles that form in response to stress and play pivotal roles in translational control, RNA metabolism, and cell survival. In cancer, SGs are increasingly recognized as central mediators of therapy resistance, enabling malignant cells to evade apoptosis, reprogram metabolism, and modulate immune responses. Understanding the mechanistic and clinical insights into SG kinetics in healthy versus cancer cells holds significant potential for targeting them in precision oncology. This review integrates current knowledge on how chemotherapeutic agents, oncogenic signaling pathways, and tumor microenvironmental stressors promote SG formation, as well as evidence of altered SG kinetics across tumor types. We further highlight how the upregulation of SG components within the tumor microenvironment shapes cancer cell behavior and adaptability, and how crosstalk between SGs and other biomolecular condensates could contribute to resistance. Finally, we discuss emerging therapeutic strategies targeting SGs, including kinase inhibitors and modulators of SG dynamics, and propose that SGs represent tractable vulnerabilities in precision oncology. By bridging mechanistic insights with clinical implications, this review positions SGs as a promising frontier in overcoming cancer therapy resistance.

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Cite This Study

Rajendiran et al. (2026) studied this question.

synapsesocial.com/papers/6969d518940543b97770a08dhttps://doi.org/10.3390/cancers18020260
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