Repurposing of the Macrolide Antibiotic Clarithromycin for the Prevention of Lung Cancer

Authors

Shanshan Deng
Tabish Hussain
Thais F Bartelli
Manu M Sebastian
Melody Zarghooni
Walter V Velasco
Brandon Somerville
Linda Phan
Michelle I Savage
Yurong Song
John L Clifford
Humam Kadara
Florencia McAllister
Powel H Brown
Seyed Javad Moghaddam
C Marcelo Aldaz

Language

English

Publication Date

2-4-2026

Journal

Molecular Cancer Therapeutics

DOI

10.1158/1535-7163.MCT-25-0392

PMID

41024580

PMCID

PMC12598927

PubMedCentral® Posted Date

11-11-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Drug repurposing is the process of reusing existing pharmaceuticals for novel clinical purposes, which offers advantages such as streamlined clinical trial access and reduced drug development costs. Clarithromycin (CAM), a member of the macrolide antibiotics family, is a promising candidate for repurposing in cancer therapy due to its known preclinical and clinical immunomodulatory and anticancer properties. In the current study, we investigated whether CAM could be repurposed as a preventive treatment for KRAS-mutant lung cancer, a subtype of lung adenocarcinoma that is strongly associated with heavy smoking. CCSPCre; LSL-KrasG12D mice at an early stage of tumor development were treated with different doses of CAM for 10 weeks. While exhibiting an excellent safety profile, CAM was able to prevent the development of premalignant and malignant lung lesions in a dose-dependent manner. In addition, CAM significantly reduced the infiltration of neutrophils/polymorphonuclear myeloid-derived suppressor cells and inhibited the mRNA expression of protumor inflammatory cytokines IL-6, TNFα, and IL-1β, as well as M2 macrophage markers Fizz1 and Arginase1 in the lung tumor microenvironment. Moreover, we investigated the effect of CAM in reshaping the intestinal and lung microbiome. Long-term CAM usage decreased intestinal microbiome diversity but, more notably, significantly increased the abundance of the probiotic genus Muribaculaceae while decreasing the abundance of Desulfovibrio, a genus associated with the promotion of various malignancies. Taken together, we conclude that CAM could provide promising cancer prevention efficacy in KRAS-mutant lung cancer due to its immunomodulatory properties on the tumor microenvironment and its regulatory effects on the microbiome.

Keywords

Animals, Lung Neoplasms, Mice, Clarithromycin, Drug Repositioning, Anti-Bacterial Agents, Humans, Tumor Microenvironment

Published Open-Access

yes

Recommended Citation

Deng, Shanshan; Hussain, Tabish; Bartelli, Thais F; et al., "Repurposing of the Macrolide Antibiotic Clarithromycin for the Prevention of Lung Cancer" (2026). Faculty, Staff and Student Publications. 5258.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5258