ATDC and Lung Squamous Cell Carcinoma (SCC)
The Role of ATDC in the Development and Progression of Lung Squamous Cell Carcinoma
Lung squamous cell carcinomas (SCCs) are a highly aggressive subset of non-small cell lung cancer (NSCLC), and the second leading cause of death related to lung cancer. Patients with lung SCC have a worse prognosis than those with lung adenocarcinoma (ADC). The poor prognosis associated with lung SCC results from the ineffective standard of care chemotherapy and a lack of alternative targeted therapies. Targeted therapies that have positive responses in ADC or other major subtypes of NSCLC are often inadequate or contraindicated for lung SCC. Therefore, it is important to identify the genes and pathways driving lung SCC, which should represent new therapeutic targets.
Analysis of the Cancer Genome Atlas (TCGA) and human lung SCC tissue microarrays reveals that ATDC is one of the most highly up-regulated genes in lung SCC. Since our laboratory has done defining work identifying ATDC as a novel oncogene in human cancers, in this study we are specifically evaluating the tumorigenic function of ATDC in lung SCC. We have exciting preliminary data in adenovirus-Cre (Ad-Cre); Pten-/-; Lkb1-/- mice (PL) with lung-specific knockout of Pten and Lkb1, knockout of ATDC prevents tumor development. In planned experiments using GEMM and human lung SCC models systems, we will be exploring in more mechanistic detail the contribution of ATDC in tumor development, and it’s role in established tumors. We will also explore the role of ATDC in regulation of the tumor microenvironment. The study aims to provide evidence suggesting that ATDC is a potential therapeutic target for lung SCC.