Determining How the Intratumoral Environment Confers Stemness in Lung Cancer
Abstracts
Initial Award Abstract |
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This project seeks to determine how some cancers can recur and become resistant to treatment. Cancer recurrence and its spread throughout the body remains the chief cause of cancer death. Despite ever increasing advances in cancer treatment, very few treatments exist for preventing cancer recurrence. This is because very little is known about how cancers recur and spread. One of the more common hypotheses for how cancer recurs and becomes resistant to treatment is that a subset of cancer cells exists within a tumor that behave like stem cells. This behavior is advantageous to cancers because stem cells are resistant to chemotherapy and radiation, but are also able to repopulate a tumor. How a cancer cell obtains these stem cell like properties remains largely unknown however. Recently, it has been shown that exposing cancer cells to conditions associated with the inside of a tumor can cause cancer cells to express genes and cellular pathways that are ordinarily only associated with stem cells. These conditions consist of low oxygen content (hypoxia) and high concentrations of lactic acid. Hypoxia is known to stimulate the expression of hundreds of protein-coding and non-protein coding genes. Additionally, mutations in genes known to cause cancer such as KRAS have been found to stimulate the expression of a wide array of coding and non-coding genes similar to hypoxia. This is because KRAS is normally a tightly controlled signaling protein responsible for signaling cell division, growth and other stem cell like behaviors. When mutated, KRAS signaling becomes hyper active and results in uncontrolled growth as well as aberrant changes in global gene expression. Therefore, we are interested in how gene expression and mutant KRAS signaling interact to induce stem cell behavior when cancer cells are subjected to conditions such as lactic acidosis and/or hypoxia. We believe this knowledge will help advance the development of novel therapies that target cancer recurrence |
