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Nodal Modulator Regulates Chemo- and Radioresistance in Lung Cancer via the Chk2 Pathway

Hye Min Kim1,2, Ju-Young Kim3,4, Chang Geun Lee1

  • 1Department of Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, Republic of Korea.

Anticancer Research
|October 28, 2025
PubMed
Abstract

Insights

Nodal modulators (NOMO) drive lung cancer resistance to chemotherapy and radiotherapy. Silencing NOMO restores sensitivity by promoting apoptosis and affecting Chk1/Chk2 kinases, suggesting NOMO as a gene therapy target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Lung cancer treatment efficacy is limited by chemo- and radioresistance.
  • Nodal modulators (NOMO1-3) are implicated in radioresistance.
  • NOMO proteins are highly expressed in lung cancer but their function is unclear.

Purpose of the Study:

  • To determine the function of NOMO in lung cancer.
  • To investigate NOMO's role in chemo- and radioresistance.

Main Methods:

  • Utilized human NOMO-specific small interfering RNA (siRNA).
  • Assessed effects of NOMO silencing on tumor cell viability and apoptosis.
  • Employed antibody arrays to analyze protein phosphorylation.

Main Results:

  • NOMO silencing reversed chemo- and radioresistance via caspase-dependent apoptosis.
  • NOMO inhibition increased phosphorylation of checkpoint kinases Chk1 and Chk2.
  • Chk1 and Chk2 modulate chemo- and radioresistance.

Conclusions:

  • NOMO and the Chk2 pathway are key players in lung cancer chemo- and radioresistance.
  • NOMO represents a potential therapeutic target for lung cancer gene therapy.
Keywords:
Chk1Chk2NOMOchemoresistancelung cancerradioresistance

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