Project 456045

As cancer grows and progresses, tumor cells have increased demand for nutrients and this need is met by altering the metabolic activity. Indeed, recent studies have shown that the tumor cells have reprogrammed metabolism for growth and survival, and this has become one of the hallmarks of the cancer. Understanding the mechanisms behind the dependency of cancer cells on the altered metabolism will help us to find the 'Achilles' heel' of these tumors and design effective therapeutic strategies. Here we focus on Head and Neck cancer, one of the deadliest cancers in the world with poor survival rate caused by reoccurrence and metastasis within five years after the initial treatment. Majority of the HNSCC studies investigated the type of metabolites in the patient samples and also used cell culture systems to study the altered pathways. While we learned a great deal of information from these incredible amount of work, recent evidence suggests that the metabolic reprogramming occurs in a complicated fashion in response to tumor microenvironment, driver mutations, immune system etc. To model all these complex interactions and at the same time study the molecular pathways behind metabolic reprogramming inside the tumor cells, I propose to study the role of metabolic genes in tumor initiation, progression and survival in an immunocompetent mosaic mouse model of head and neck cancer utilizing CRISPR based gene editing technologies. The goal of this work is to find novel and effective metabolic drug targets that can be used as a combinatorial therapy to treat head and neck cancer patients.