Metabolic stress & cell survival in lung cancer

Lung cancer is the leading cause of cancer-associated cell death worldwide, claiming 1.4 million lives annually on a global basis. As tumors form, at the primary site of origin and at distant sites of metastasis, they out-strip their access to nutrients and oxygen, thus placing the malignant cells under metabolic stress. The cellular response to this stress triggers a variety of adaptive responses designed to preserve cell viability, but when persistent, the cellular response to stress triggers an active cell suicide mechanism.

Our laboratory has identified a gene called Bax Inhibitor-1 (BI-1) that regulates the cell stress response, increasing cellular resilience to metabolic stress and preserving cell survival in harsh environments. The levels of BI-1 gene activity are elevated in several types of cancer, including some types of lung cancer. Moreover, our laboratory has obtained preliminary data indicating that BI-1 is required for human lung cancer cells to form tumors in animals.

The goal of my fellowship application is to improve understanding of the mechanisms by which BI-1 promotes cell resilience and cell survival in the context of lung cancer. The long-term objective is to use this knowledge for formulating new strategies for neutralizing the protective activity of BI-1, leaving cancer cells unprotected from metabolic stress and encouraging their eradication by triggering of the cell suicide machinery.