Targeting Glucose Reliance of Lung Squamous Cell Carcinoma
Abstract
Cancer biologists have made tremendous efforts to provide a safer and more effective treatment option for lung cancer patients. Their efforts have led to development of a new treatment paradigm designed to target the unique molecular abnormalities of cancer cells that significantly reduces the occurrence of drug resistance and the toxic side effects associated with conventional chemotherapies. However, not all lung cancer patients are benefitting from this “targeted cancer therapy.” In particular, if a cancer patient is diagnosed with squamous cell carcinoma, a type of lung cancer that accounts for 20 to 30% of all lung cancer and is linked more strongly with cigarette smoking than any other types of lung cancer, there are limited available targeted therapies for their treatment options. Given that the treatment outcome of squamous cell carcinoma with conventional chemotherapies is very poor, it is imperative to identify and validate targetable susceptibilities that are uniquely associated with squamous cell carcinoma. Through rigorous characterization of a patient-derived lung cancer model system and a publicly available human cancer database, as well as human lung cancer samples, we revealed that a protein called glucose transporter 1, which is involved in the uptake of glucose, as well as a panel of proteins that are also involved in sugar metabolism, are remarkably elevated in lung squamous cell carcinoma compared to other types of lung cancer. Accordingly, squamous cell carcinoma is uniquely addicted to high sugar consumption. This renders squamous cell carcinoma vulnerable to inhibition of sugar metabolism and dietary or pharmacological sugar restriction. This study will rigorously evaluate the unique sugar addiction of squamous cell carcinoma as a potential novel treatment strategy for lung squamous cancers by determining whether restriction of sugar uptake and utilization can stop the growth of this dismal disease. In particular, we will employ an innovative approach by testing a type 2 diabetic drug that is both Food and Drug Administration-approved and widely used in diabetic patients as a new treatment option for lung squamous cancer patients. If successful, this study will open new avenues to designing a strategy for targeted therapy of squamous cell carcinoma with a rapid clinical translation.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810439
Entities
People
- Jung-whan Kim
Organizations
- United States Army
- University of Texas at Dallas