Exploring Autophagy in the Development of NSCLC

Rutgers Cancer Institute of New Jersey researcher ‘Jessie’ Yanxiang Guo, PhD, has received a $150,000 grant from the Lung Cancer Research Foundation (LCRF) to investigate the role of a cell survival mechanism known as autophagy in the development of lung cancers driven by mutations in tumor suppressors known as LKB1 and oncogene KRAS. The aim is to provide new therapeutic approaches to treating non-small cell lung cancer, a sub-type of lung cancer that is active of KRAS and deficient of the LKB1 gene.

Lung cancer remains the leading cause of cancer death worldwide and non-small cell lung cancer accounts for more than 85 percent of these cases. Driver mutations are molecular alterations in tumors that play a significant role in tumor progression and growth. Over the past decade, discovery of a number of driver mutations underlying this disease has led to significant advances in prognostication and treatment of these cancers. However, patients harboring mutations in the tumor suppressor LKB1 and the oncogene KRAS, which are two of the most common mutations in non-small cell lung cancer, develop more aggressive tumors, show a high frequency of cancer spread and have limited treatment options.

Cancer cells have distinct metabolism compared to normal tissues. Targeting cancer metabolism has recently become a very important approach to cancer treatment. Sufficient energy production is essential for tumor growth. The self-cannibalizing process of autophagy is activated in order to recycle cellular components to maintain energy homeostasis when extracellular nutrients are limited.

Using laboratory models for LKB1-deficient KRAS-mutant non-small cell lung cancer, Dr. Guo found that autophagy ablation reduced the frequency of tumor initiation and tumor growth, and extended the life span of laboratory models. In this project funded by LCRF, Guo will further elucidate the underlying mechanism by which autophagy maintains energy homeostasis for the development of LKB1-deficient KRAS-mutant lung cancer and assess the clinical translatability of these findings in treating LKB1-deficient KRAS-mutant non-small cell lung cancer.

“By further uncovering the mechanisms of autophagy in the development of non-small cell lung cancer patients bearing co-mutations of KRAS and LKB1, we may be able to identify new treatment approaches for this population,” notes Guo, who is also an assistant professor of medicine at Rutgers Robert Wood Johnson Medical School.

The project period runs through October 2020.