William Bieneman
Pronouns: he/him/his
Research Mentor(s): Ananya Banerjee
Research Mentor School/College/Department: Department of Internal Medicine/ Division of Hematology/ Oncology / Medicine
Program:
Authors: Ananya Banerjee, William Bieneman, Sohair Holman, Sofia D. Merajver, Nathan M. Merrill
Session: Session 4: 1:40 pm – 2:30 pm
Poster: 25
Abstract
Lung cancer causes the most deaths of any cancer. The fusion of the anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) genes is present about 3-5% of all cases of non-small-cell lung carcinoma (NSCLC). ALK specific tyrosine-kinase inhibitors (ALK-TKIs), which inhibit the kinase activity of EML4-ALK, have proven successful in treating EML4-ALK+ NSCLC. Unfortunately, patients may develop resistance to ALK-TKIs, creating new challenges for cancer research. This resistance indicates a need for new treatment strategies. Previous studies have shown that the combination of ALK-TKIs with other drugs can re-sensitize resistant EML4-ALK cell lines, even when those drugs do not directly target EML4-ALK. EML4-ALK is involved in signaling pathways related to cell proliferation, which are suppressed by tumor suppressor candidate 2 (TUSC2). TUSC2 is also known to promote apoptosis in cancer cells but has not been extensively studied in EML4-ALK+ NSCLC. To investigate the connection, ALK-TKI resistant EML4-ALK+ and non-EML4-ALK+ NSCLC cell lines have been transfected with a TUSC2 plasmid and their caspase 3/7 activity has been determined. Overexpression of TUSC2 has been confirmed with qRT-PCR and Western blot. TUSC2 mediated increased caspase activity in the ALK inhibitor resistant cells demonstrates their TUSC2 induced apoptosis. Besides, reduced ability in colony formation on overexpressing TUSC2 in ALK+ cells also supports the pro-apoptotic role of TUSC2 in ALK+ NSCLC. The underlying mechanisms of TUSC2-mediated apoptosis in ALK+ NSCLC are still unknown. This information will open the door to new research and potential therapies. Keywords: EML4-ALK fusion, NSCLC, lung cancer, tyrosine kinase inhibitor, drug resistance, TUSC2
