Grant: Project Grant - Priority Announcement: Cancer Research

The poor prognosis for lung cancer patients is associated with a late stage of disease at the time of diagnosis, highlighting the need for effective methods for early detection. It has recently been demonstrated that low-dose computed tomographic (LDCT) screening of patients at high-risk of developing lung cancer improves survival outcomes. While a major advancement, LDCT is currently restricted to heavy smokers despite 25% of lung cancers occurring in people who have never smoked. Aside from smoking, a person's genetics also influences their risk of developing lung cancer, which is highlighted by a history of this disease in certain families. However, very little is known about the underlying genetic causes of lung cancer susceptibility and defining these factors may lead to new screening approaches that catch lung cancer early in more patients, improving diagnosis. Through genetic analysis of lung tumors, we recently uncovered the mutation of a gene that is located in a region linked to familial risk of lung cancer development. This gene is known to play a role in repairing damaged DNA, and we hypothesize that its inactivation leads to increased gene mutations over time, increasing the risk of developing cancer. To test this, we will disrupt the gene in normal lung cells to determine if this allows them to transform into lung cancer. We will also do this with the additional exposure to tobacco to see if inactivation of this gene makes cells more prone to developing mutations and subsequently, cancer. Lastly, we will determine whether tumors lacking this gene are vulnerable to cancer drugs that induce DNA damage, potentially offering a strategy to treat patients with this gene mutation in the future. Together, this study will determine whether this gene is associated with lung cancer susceptibility and development, and how this information can be used to improve screening protocols aimed at the early detection of lung cancer in high risk patients.