Targeting Chemoresistance in Small Cell Lung Cancer
Abstract
Small cell lung cancer (SCLC) is the deadliest form of lung cancer and the most strongly associated with smoking history. Unfortunately, chemotherapy remains the main treatment option for patients with SCLC. Although this cancer typically responds extremely well, relapse is fast and largely inevitable. There are no effective therapies for relapsed tumors. The goal of our proposed study is to find new targets for drug therapy against relapsed SCLC tumors and provide continued hope for these patients. In this regard, we have identified a protein called HEPACAM2, which demonstrates unique, high expression in SCLC cell lines and tumors, making it a very attractive target. Knockdown of HEPACAM2 leads to cell cycle arrest, followed by apoptosis. Tankyrase 1 (TNKS) has been shown to poly(ADP-ribosylate) HEPACAM2 and this modification is necessary for HEPACAM2 spindle localization and mitosis. Specific inhibitors of TNKS have been developed with little activity towards PARP1,a participant in the DNA damage response.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2019
- Accession Number
- AD1092039
Entities
People
- Afshin Dowlati
Organizations
- Case Western Reserve University