Optimized Bexarotene Aerosol Formulation Inhibits Major Subtypes of Lung Cancer in Mice

Nano Lett. 2019 Apr 10;19(4):2231-2242. doi: 10.1021/acs.nanolett.8b04309. Epub 2019 Mar 21.


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.

Keywords: Squamous cell carcinoma; adenocarcinoma; aerosol; bexarotene; preclinical.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma of Lung / drug therapy*
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / pathology
  • Administration, Oral
  • Aerosols / administration & dosage*
  • Animals
  • Anticarcinogenic Agents / administration & dosage
  • Anticarcinogenic Agents / adverse effects
  • Bexarotene / administration & dosage*
  • Bexarotene / adverse effects
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Disease Models, Animal
  • Drug Compounding
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Hypercholesterolemia / chemically induced
  • Hypercholesterolemia / pathology
  • Hypercholesterolemia / prevention & control
  • Lung / drug effects
  • Lung / pathology
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Mice
  • Signal Transduction / drug effects


  • Aerosols
  • Anticarcinogenic Agents
  • Bexarotene