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Updated: Aug 11, 2026

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

Mycoplasma infection drives EGFR-TKI resistance through convergent transcriptomic reprogramming in non-small cell

Bing Wang1,2, Valentina Donati1,2,3, Alessandro Gregori1,2

  • 1Department of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.

Iscience
|August 10, 2026
PubMed

Insights

Mycoplasma infection causes resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). Clearing the infection and inhibiting mTOR and LDHA can overcome this drug resistance.

Area of Science:

  • Oncology
  • Infectious Disease
  • Molecular Biology

Background:

  • Epidermal growth factor receptor (EGFR) mutations drive non-small cell lung cancer (NSCLC).
  • Resistance to EGFR tyrosine kinase inhibitors (TKIs) is a significant clinical challenge in NSCLC treatment.
  • Mycoplasma infection is a potential, yet understudied, factor influencing cancer therapy outcomes.

Purpose of the Study:

  • To investigate the role of mycoplasma infection in acquired resistance to EGFR TKIs in NSCLC.
  • To elucidate the molecular mechanisms by which mycoplasma infection confers drug resistance.
  • To identify potential therapeutic strategies to overcome mycoplasma-induced TKI resistance.

Main Methods:

  • Utilized EGFR-mutant NSCLC cell lines to model TKI resistance.
  • Assessed the impact of mycoplasma infection on key signaling pathways (ERK, AKT, NF-κB) and receptor internalization.
  • Employed antibiotic treatment to eliminate mycoplasma and evaluated changes in drug sensitivity.
  • Conducted transcriptomic analysis to identify molecular pathways involved in resistance.
  • Investigated the efficacy of combined mTOR and LDHA inhibition.

Main Results:

  • Mycoplasma infection sustained pro-survival signaling, impaired EGFR internalization, and reduced osimertinib sensitivity in EGFR-mutant NSCLC cells.
  • Antibiotic clearance of mycoplasma partially restored sensitivity to EGFR TKIs, confirming a causal link.
  • Transcriptomic data revealed converging pathways related to mycoplasma infection and drug resistance, including impaired receptor internalization and clathrin downregulation.
  • Combined inhibition of mTOR and LDHA significantly enhanced growth suppression in mycoplasma-infected cells.
  • Clinical data showed that mycoplasma infection and elevated LDHA expression correlated with poorer survival in EGFR-TKI-treated NSCLC patients.

Conclusions:

  • Mycoplasma infection is a non-genetic factor causally linked to acquired resistance to EGFR TKIs in NSCLC.
  • Targeting mycoplasma infection with antibiotics, alongside inhibiting mTOR and LDHA, represents a promising therapeutic strategy.
  • These findings highlight the importance of considering infectious agents in cancer treatment resistance and suggest a novel therapeutic approach.
Keywords:
EGFR-TKI resistanceMycoplasmamachine learningnon-small cell lung cancertranscriptomics

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