Unraveling the triad of hypoxia, cancer cell stemness, and drug resistance

J Hematol Oncol. 2025 Mar 18;18(1):32. doi: 10.1186/s13045-025-01684-4.

Abstract

In the domain of addressing cancer resistance, challenges such as limited effectiveness and treatment resistance remain persistent. Hypoxia is a key feature of solid tumors and is strongly associated with poor prognosis in cancer patients. Another significant portion of the development of acquired drug resistance is attributed to tumor stemness. Cancer stem cells (CSCs), a small tumor cell subset with self-renewal and proliferative abilities, are crucial for tumor initiation, metastasis, and intra-tumoral heterogeneity. Studies have shown a significant association between hypoxia and CSCs in the context of tumor resistance. Recent studies reveal a strong link between hypoxia and tumor stemness, which together promote tumor survival and progression during treatment. This review elucidates the interplay between hypoxia and CSCs, as well as their correlation with resistance to therapeutic drugs. Targeting pivotal genes associated with hypoxia and stemness holds promise for the development of novel therapeutics to combat tumor resistance.

Keywords: Cancer; Cancer stem cell; Drug resistance; Hypoxia.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Hypoxia
  • Drug Resistance, Neoplasm*
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Neoplastic Stem Cells* / drug effects
  • Neoplastic Stem Cells* / metabolism
  • Neoplastic Stem Cells* / pathology

Substances

  • Antineoplastic Agents