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

Abirami Rajendiran1, Gayathri Ramakrishnan2, Takbum Ohn3

  • 1Texas Tech University Health Sciences Center, El Paso, TX 79911, USA.

Cancers
|January 28, 2026
PubMed

Insights

Stress granules (SGs), crucial for cell survival, paradoxically promote cancer therapy resistance. Targeting SG dynamics offers a promising strategy for precision oncology to overcome treatment failure.

Area of Science:

  • Cell Biology
  • Oncology
  • Biochemistry

Background:

  • Stress granules (SGs) are dynamic, membraneless organelles involved in cellular stress responses, translational control, and RNA metabolism.
  • In cancer, SGs are implicated in mediating resistance to therapies, facilitating immune evasion, and metabolic reprogramming.

Purpose of the Study:

  • To review the mechanistic and clinical insights into SG kinetics in healthy versus cancer cells.
  • To explore the role of SGs in cancer therapy resistance and their potential as therapeutic targets in precision oncology.

Main Methods:

  • Literature review integrating current knowledge on SG formation triggers in cancer.
  • Analysis of evidence on altered SG kinetics across tumor types and their interaction with the tumor microenvironment.
  • Discussion of emerging therapeutic strategies targeting SGs.

Main Results:

  • Chemotherapeutic agents, oncogenic signaling, and tumor microenvironmental stressors promote SG formation.
  • Upregulation of SG components influences cancer cell behavior, adaptability, and resistance.
  • Crosstalk between SGs and other biomolecular condensates contributes to therapeutic resistance.

Conclusions:

  • Stress granules are central mediators of cancer therapy resistance, influencing apoptosis, metabolism, and immune responses.
  • Targeting SG dynamics and components presents a promising avenue for novel cancer therapies.
  • SGs represent tractable vulnerabilities within the tumor microenvironment for precision oncology strategies.
Keywords:
biomolecular condensatescell survivaldrug resistancemetastasisstress granulesstress response

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