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Presentation date

Summer 8-12-2021

Faculty Mentor

Dr. Mohd Nasser

Research Mentor

Dr. Parvez Khan

Abstract

Lung cancer is the leading cause of cancer deaths accounting for about 22% of all cancer related cases in both males and females. Lung cancers are broadly grouped into two types mainly small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) with SCLC accounting for about 15% of all lung cancer cases. SCLC is different from NSCLC because in most cases it originates centrally in the bronchi and is frequently seen in smokers. SCLC is aggressive and one of the most malignant forms of tumor characterized by uncontrolled rapid growth of certain cells in the lungs. SCLC displays poor prognosis because of early-stage metastasis, acquisition of chemoresistance, and has a high rate of recurrence. One of major drivers of chemoresistance is the transcription factor Forkhead box protein M1 (FOXM1) that is responsible for modulating cell cycle proliferation, maintenance of genomic stability, DNA damage response, and cell differentiation in numerous tumor entities. In order to explore properties of SCLC cancer cell lines, human non-bone metastatic SBC3, bone metastatic SBC5, H1688, and murine (RPM) cells were treated with a FOXM1 inhibitor known as FDI-6. As a transcription factor FOXMI binds sequence-specific motifs on DNA through its DNA-binding domain activating proliferation and differentiation-associated genes. Anomalous overexpression of FOXMI is a crucial characteristic in oncogenesis and the development of SCLC. FDI-6 is a novel small molecule inhibitor of FOXM1, and it works by binding directly to FOXM1 protein, to displace FOXM1 from genomic targets in SCLC cells prompting concomitant translational downregulation. Functional assays performed confirm that FDI-6 is a viable FOXMI inhibitor showing therapeutic efficacies in SCLC.

Keywords

SCLC, FOXM1 protein, FDI-6 treatment, SBC3 cells, SBC5 cells, RPM cells, H1688 cells, vehicle control (VC), migration, colony formation, apoptosis, proliferation, inhibition, oncogenesis, metastasis, transcription factor, cell viability

Evaluation of FOXM1 inhibitor (FDI-6) as a potential therapeutic molecule for small cell lung cancer

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