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Ribonucleotide reductase regulatory subunit M2 as a macromolecular target bridging small cell lung cancer progression

Hongquan Xing1, Shanshan Cai1, Cong Wu2

  • 1Department of Respiratory Diseases, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China.

International Journal of Biological Macromolecules
|May 11, 2026
PubMed

Insights

Small cell lung cancer (SCLC) patients face increased COVID-19 mortality. Research links aggressive SCLC tumor biology to heightened virus susceptibility, potentially through the RRM2 gene.

Area of Science:

  • Oncology
  • Infectious Diseases
  • Molecular Biology

Background:

  • Small cell lung cancer (SCLC) is aggressive and immunosuppressive.
  • The vulnerability of SCLC patients to COVID-19 and its molecular basis are unknown.
  • Understanding this link is crucial for patient outcomes.

Purpose of the Study:

  • To investigate the relationship between SCLC and COVID-19 vulnerability.
  • To identify molecular mechanisms underlying this association.

Main Methods:

  • Analysis of nationwide epidemiological data (CDC WONDER, SEER).
  • Transcriptomic profiling and molecular docking.
  • In vitro experimental validation of gene expression and drug efficacy.

Main Results:

  • SCLC patients exhibited the highest COVID-19 mortality among lung cancer subtypes.
  • SCLC was confirmed as an independent risk factor for adverse COVID-19 outcomes.
  • Elevated RRM2 expression in SCLC cells correlated with proliferation and migration; RRM2 showed strong binding to SARS-CoV-2 3CLpro.

Conclusions:

  • SCLC patients are highly vulnerable to severe COVID-19.
  • RRM2 may serve as a molecular link connecting SCLC's aggressive nature to increased susceptibility to SARS-CoV-2.
  • RRM2 inhibitors show potential for therapeutic intervention.
Keywords:
Ribonucleotide reductase regulatory subunit M2SARS-CoV-2 infectionSmall cell lung cancer

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