SPP1 promotes cancer stemness and reduces osimertinib sensitivity in non-small cell lung cancer through interactions

Hong Bi1, Lewei He1, Liyan Wang1

  • 1Department of Pulmonary and Critical Care Medicine, The First People's Hospital of Kunming City and Affiliated Calmette Hospital of Kunming Medical University, Kunming, 650224, Yunnan Province, China.

Cancer Cell International
|January 15, 2026
PubMed

Insights

SPP1 interaction with CD44 drives osimertinib resistance in non-small cell lung cancer (NSCLC) by regulating cancer stem cells (CSCs). Understanding this mechanism is crucial for developing effective NSCLC treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Non-small cell lung cancer (NSCLC) is a major global health concern.
  • Osimertinib is a primary treatment for NSCLC, but acquired resistance limits its long-term efficacy.
  • Mechanisms underlying osimertinib resistance require elucidation to optimize therapeutic strategies.

Purpose of the Study:

  • To investigate the role of SPP1 in the development of osimertinib resistance in NSCLC.
  • To identify the molecular interactions contributing to treatment resistance.
  • To provide a basis for novel therapeutic approaches against resistant NSCLC.

Main Methods:

  • Evaluation of cancer stem cell (CSC) properties, including cell activity, spheroid formation, and cloning efficiency.
  • Assessment of stem cell marker molecule expression.
  • In vivo sensitivity testing of SPP1 in mouse models of NSCLC treated with osimertinib.

Main Results:

  • SPP1 was identified as a key regulator of CSCs.
  • SPP1 interacts with CD44 to promote the generation of osimertinib-resistant CSCs.
  • The SPP1-CD44 axis contributes significantly to acquired resistance against osimertinib.

Conclusions:

  • The SPP1-CD44 interaction is a critical mechanism driving osimertinib resistance in NSCLC.
  • Targeting the SPP1-CD44 pathway may represent a viable strategy to overcome drug resistance.
  • These findings support further clinical investigation for improved NSCLC treatment.

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