Metformin Plus/Minus Fasting Mimicking Diet to Target the Metabolic Vulnerabilities of LKB1-inactive Lung Adenocarcinoma
Status:
Recruiting
Trial end date:
2023-09-10
Target enrollment:
Participant gender:
Summary
Lung adenocarcinoma with inactive LKB1 has emerged as a particularly aggressive form of lung
cancer, with poor response to immune checkpoint inhibitors. Recent preclinical evidences have
demonstrated that LKB1-inactive lung adenocarcinoma is characterized by specific metabolic
vulnerabilities, which make it hypersensitive to energetic crisis. For instance, by
inhibiting mitochondrial metabolism and reducing ATP availability to cancer cells, the
antidiabetic compound metformin has anticancer activity and prevents acquired resistance to
cisplatin in lung adenocarcinoma with inactive LKB1. Similarly to metformin, glucose
starvation, which can be recapitulated in vivo by cyclic fasting or fasting-mimicking diet
(FMD), can cause metabolic crisis in these neoplasms. In this trial, the investigators will
assess for the first time the efficacy of combining standard-of-care platinum-based
chemoimmunotherapy with metformin plus/minus FMD in patients with LKB1-inactive, advanced
lung adenocarcinoma.