Anna Grobelny

Program: Molecular Genetics and Genomics

Current advisor: Jason D. Weber, PhD

Undergraduate university: Webster University, 2019

Enrollment year: 2019

Research summary
Genetic origin and clinical significance of p14ARF tumor suppression in lung cancer

The p14ARF tumor suppressor is the second most commonly mutated gene in Non-Small Cell Lung Cancer (NSCLC). p14ARF (p19ARF in mice) is encoded by the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene. The p14ARF tumor suppressor is known to play a fundamental role in cancer progression by regulating senescence, apoptosis, and proliferation. The primary function of p14ARF is to respond to oncogenic signals and activate the p53 tumor suppressor by inhibiting and sequestering the HDM2 (MDM2 in mice) oncogene. However, recent studies have uncovered multiple p53-independent functions of p14ARF, opening the door to a myriad of possible vulnerabilities in p14ARF-mutant tumors. Many current therapeutic efforts in cancer biology focus on inhibiting the function of aberrant oncogenes whose activities are known to increase proliferation and cell growth. Unfortunately, these efforts have had limited success in lung cancer, where the five-year survival rate remains unchanged. To address this significant unmet medical need, I will take a novel approach; rather than inhibiting oncogenes, I will attempt to reestablish the function of the p14ARF tumor suppressor in NSCLC to block tumor growth and proliferation. The long-term goal of this project is to determine the genetic requirements and clinical significance of p14ARF tumor suppression in humans that will lead to the development of p14ARF-targeted cancer therapeutics.

Graduate publications