Optimized Bexarotene Aerosol Formulation Inhibits Major Subtypes of Lung Cancer in Mice. Nano Lett 2019 Apr 10;19(4):2231-2242
Date
03/16/2019Pubmed ID
30873838DOI
10.1021/acs.nanolett.8b04309Scopus ID
2-s2.0-85063522412 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
Bexarotene has shown inhibition of lung and mammary gland tumorigenesis in preclinical models and in clinical trials. The main side effects of orally administered bexarotene are hypertriglyceridemia and hypercholesterolemia. We previously demonstrated that aerosolized bexarotene administered by nasal inhalation has potent chemopreventive activity in a lung adenoma preclinical model without causing hypertriglyceridemia. To facilitate its future clinical translation, we modified the formula of the aerosolized bexarotene with a clinically relevant solvent system. This optimized aerosolized bexarotene formulation was tested against lung squamous cell carcinoma mouse model and lung adenocarcinoma mouse model and showed significant chemopreventive effect. This new formula did not cause visible signs of toxicity and did not increase plasma triglycerides or cholesterol. This aerosolized bexarotene was evenly distributed to the mouse lung parenchyma, and it modulated the microenvironment in vivo by increasing the tumor-infiltrating T cell population. RNA sequencing of the lung cancer cell lines demonstrated that multiple pathways are altered by bexarotene. For the first time, these studies demonstrate a new, clinically relevant aerosolized bexarotene formulation that exhibits preventive efficacy against the major subtypes of lung cancer. This approach could be a major advancement in lung cancer prevention for high risk populations, including former and present smokers.
Author List
Zhang Q, Lee SB, Chen X, Stevenson ME, Pan J, Xiong D, Zhou Y, Miller MS, Lubet RA, Wang Y, Mirza SP, You MMESH terms used to index this publication - Major topics in bold
Administration, OralAerosols
Animals
Anticarcinogenic Agents
Carcinoma, Squamous Cell
Disease Models, Animal
Drug Compounding
High-Throughput Nucleotide Sequencing
Humans
Hypercholesterolemia
Lung
Lymphocytes, Tumor-Infiltrating
Mice
Signal Transduction
