Finding treatments for small cell lung cancer (SCLC), which is the most aggressive form of lung cancer, is crucial, but so is determining which patients will most benefit from these treatments. Work from the Cancer Research UK Manchester Institute and AstraZeneca focused on both aspects, with positive results.
Dr. Caroline Dive, a co-investigator on the study, stated the importance of their work in an article on the Daily Mail by Stephanie Linning entitled, “Lung cancer breakthrough as scientists discover new drug which could treat most aggressive form of the disease,” saying, “More targeted therapies are needed to help those patients whose tumors become resistant to chemotherapy.”
The team’s targeted therapy is based on energy production in tumor cells. Cancer cells rely mainly on glycolysis because it requires little energy in order to make energy. During the process of glycolysis, cells produce lactate as a by-product and excrete it using monocarboxylate transporters (MCTs). The drug in question, AZD3695 from AstraZeneca, targets MCT1 molecules on lung cancer cells.
To evaluate the utility of AZD3965, the research team tested seven SCLC cell lines in conditions of normoxia (normal oxygen) and hypoxia (low oxygen), as well as an animal model implanted with tumor cells. After treating tumor cells with AZD3965, the researchers found an increased level of lactate that inhibited growth. The animal tumor model had less tumor growth when treated with AZD3965. These results were published in Clinical Cancer Research.
Beginning the translation to humans, the team also studied tissue explants from 78 SCLC patients. A tissue microarray identified a high level of MCT1 expression in patients with poor prognoses. Dr. Dive stated, “We propose that this drug will be most useful in this subset of patients who have elevated MCT1 levels and need more effective treatments. Our laboratory results are promising and certainly provide encouragement to test this treatment clinically in patients with SCLC.”
Added Susan Galbraith, head of the oncology innovative medicines unit at AstraZeneca, “Targeting tumor cell metabolism represents a novel and exciting approach, and we are delighted to be working with The University of Manchester and Cancer Research UK to investigate the utility of AZD3965 as a potential novel cancer treatment.”
According to Dr. Dive, “This new drug–AZD3965–is currently in clinical trials, but it has not yet been tested in small cell lung cancer.”