Sohair Holman
Pronouns: She/her
Research Mentor(s): Ananya Banerjee
Research Mentor School/College/Department: Department of Internal Medicine/ Division of Hematology/ Oncology / Medicine
Program:
Authors: Ananya Banerjee, Sohair Holman, William Bieneman, Sofia D. Merajver , Nathan M. Merrill
Session: Session 4: 1:40 pm – 2:30 pm
Poster: 25
Abstract
Lung carcinogenesis, marked by its intricate pathobiology and distinct heterogeneity, affects a significant proportion of global cancer-associated morbidity and mortality. Amongst many types of lung cancer, Non-Small Cell Lung Carcinoma (NSCLC) is one, encompassing an estimated 85% of the identified cases. One rare fusion of two genes: echinoderm mictrotubule-assosiated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK), EML4-ALK, found in NSCLC is lethal and is diagnosed mostly in young patients and non-smokers. The fusion happens because of an inversion on the short arm of chromosome 2, causing a chimeric protein with oncogenic properties. Current therapeutic strategies for EML4-ALK-positive NSCLC primarily rely on ALK Tyrosine Kinase Inhibitors (TKIs) such as alectinib, lorlatinib, crizotanib, and others. Despite the initial success of these targeted therapies in impeding tumor progression, the emergence of resistance remains a significant challenge. In response to this clinical obstacle, we direct our focus to the Tumor Suppressor Candidate 2 (TUSC2) gene, a vital tumor suppresser. Scientific literature underscores the TUSC2 gene’s role in processes like cell proliferation, apoptosis, and immune response regulation. When the TUSC2 pathway is suppressed, tumor growth increases, affirming its crucial role in our study of lung cancer. To investigate the relationship between EML4- ALK and TUSC2, 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 support the pro-apoptotic role of TUSC2 in ALK+ NSCLC. The results highlight that TUSC2 overexpression leads to apoptosis in EML4-ALK positive cells, suggesting TUSC2 as a prospective therapeutic agent. However, the underlying molecular mechanisms is not well explored in EML4-ALK NSCLC and warrants further research. Key Words: NSCLC, Lung Cancer, EML4-ALK fusion, ALK TKIs, TUSC2, and Apoptosis
