Mechanistic modeling of anti-microRNA-155 therapy combinations in lung cancer

Joseph Cave, Vrushaly Shinglot, Joseph D Butner, Vittorio Cristini, Bulent Ozpolat, George A Calin, Prashant Dogra, Zhihui Wang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

To improve treatment outcomes in non-small cell lung cancer (NSCLC), it is crucial to identify treatment strategies with the potential to exhibit drug synergism. This can lower the required effective dose, reducing exposure to drugs and associated toxicities, while improving treatment efficacy. In previous studies, drugs targeting the microRNA-155 or PD-L1 have been promising in restraining NSCLC tumor growth. We have developed a mathematical model that simulates the in vivo pharmacokinetics and pharmacodynamics of the novel nanoparticle-delivered anti-microRNA-155 for potential use with standard-of-care drug atezolizumab for NSCLC. Through modeling and simulation, we identified possible drug synergism between the two drugs that holds promise to improve tumor response at reduced drug exposure.Clinical Relevance-Identifying the possibility of drug synergism for an anti-microRNA-155 based nanotherapeutic with standard-of-care immunotherapy to improve lung cancer treatment outcomes.

Keywords

  • Humans
  • Lung Neoplasms/drug therapy
  • Carcinoma, Non-Small-Cell Lung/drug therapy
  • Antibodies, Monoclonal/pharmacology
  • Treatment Outcome
  • Immunotherapy
  • MicroRNAs

ASJC Scopus subject areas

  • General Medicine

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