Characterizing the impact of aging on the effects of PTEN loss in lung adenocarcinoma
Description: Lung cancer is the leading cause of cancer death and one of the most serious harms associated with tobacco smoking. Cancer typically occurs in older people- in fact, age is the single strongest risk factor for cancer. Many physiological changes occur when people age and mounting evidence suggests that some of these changes can modify the effect of cancer-causing mutations and influence tumor growth. Despite the close connection between aging and cancer biology, little is known about how aging impacts lung cancer development and the efficacy of different forms of treatment. Lung cancer in humans can be studied using mice that are genetically-engineered to allow the induction of diverse, cancer-causing mutations in the adult lung, resulting in the development of tumors that arise in their natural setting and closely resemble human tumors. To elucidate the impact of aging on lung tumor development, my thesis laboratory measured the effects of mutating many different cancer-causing genes in young and old mice with KRAS-driven lung adenocarcinoma, a common and tobacco-associated subtype of lung cancer. This experiment revealed that deletion of PTEN, a gene that is frequently mutated in lung cancer and is known to strongly stimulate tumor growth when deleted in young mice, had relatively weak effects on tumor growth in old mice. PTEN suppresses the PI3K/AKT pathway, which is one of the most important signaling pathways controlling the proliferation and survival of cells. These preliminary data suggest that the effects of PTEN deletion, and more generally, of activation of the PI3K/AKT pathway, on lung cancer development may be age-dependent, and raises the possibility that patient age may affect the extent to which lung cancer responds to therapies that target this critical pathway. My research will explore the mechanisms underlying the differential effect of PTEN-mutation with age through comparative analysis of PTEN-deficient tumors in young and old mice. In addition, I will compare the efficacy of drugs that target the PI3K/AKT pathway in treating PTEN deficient and proficient lung cancer in young and aged mice. These analyses will deepen our understanding of the biology of PTEN-deficient tumors and the factors that govern their growth, with the potential to have important implications for the treatment of lung cancer in both older and younger patients.
Amount: $82,910
Start date: 2023-07-01
Investigators: Emily Shuldiner, Emily Shuldiner
Institution: Stanford University
Funded outputs count: 0
Funder award ID: g97z82
OpenAlex ID: G4631390895