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The Role of Mesenchymal Stem Cells in Drug Resistance in Lung Neoplasms

Dongho Kang1, Eunhee Yeon1, Sunyoung Kim1

  • 1WINDBIO, Seoul, Korea.

Journal of Cancer Prevention
|October 20, 2025
PubMed

Insights

Mesenchymal stem cells (MSCs) in the tumor microenvironment promote lung cancer drug resistance by driving epithelial-mesenchymal transition (EMT). Targeting MSC paracrine signaling or extracellular vesicles may restore sensitivity to therapies.

Area of Science:

  • Oncology
  • Cell Biology
  • Cancer Research

Background:

  • The tumor microenvironment (TME) significantly influences lung cancer treatment outcomes and drug resistance.
  • Mesenchymal stem cells (MSCs) within the TME are key regulators of cancer progression through paracrine signaling.
  • MSC-derived factors promote epithelial-mesenchymal transition (EMT), enhancing cancer cell motility, invasiveness, and stemness.

Purpose of the Study:

  • To review the mechanisms by which MSCs induce EMT and contribute to drug resistance in lung cancer.
  • To explore translational strategies targeting MSC-mediated resistance for improved lung cancer therapy.

Main Methods:

  • Literature review synthesizing current mechanistic insights into MSC-mediated EMT-driven resistance.
  • Analysis of key signaling pathways (e.g., STAT3, PI3K/AKT, Wnt/β-catenin) activated by MSC-secreted factors.
  • Discussion of therapeutic strategies including paracrine signaling inhibition and extracellular vesicle (EV) engineering.

Main Results:

  • MSC-derived cytokines, growth factors, and EVs drive EMT in lung cancer cells.
  • EMT confers resistance to EGFR tyrosine kinase inhibitors and platinum-based chemotherapy.
  • MSC-induced EMT activates oncogenic signaling pathways and remodels immune surveillance, supporting residual tumor cell survival.

Conclusions:

  • Understanding the MSC-lung cancer cell interplay within the TME is crucial for developing effective lung cancer treatments.
  • Targeting MSC paracrine signaling and EVs offers promising strategies to overcome drug resistance and restore therapeutic sensitivity in lung cancer.
Keywords:
Drug resistanceEpithelial-mesenchymal transitionLung neoplasmsMesenchymal stem cellsneoplasm

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