Non-small cell lung cancers (NSCLC) constitute 80-85% of lung cancers and are the leading cause of cancer-related deaths globally. The most common cause is prolonged smoking. Current treatment options for NSCLC include surgery, radiation, chemotherapy, targeted drug therapy, and immunotherapy. Although these medications are effective in the short term, patients often face issues of drug resistance and debilitating side effects with prolonged use. Currently, the use of Zika virus (ZIKV) is being researched as a possible alternative treatment for cancer, which minimizes side effects and the risk of drug resistance. TIM/TAM proteins are identified as the putative ZIKV receptors on the surface of human cells that mediate viral entry through apoptotic mimicry. Once engulfed, the virus can hijack the host cell’s machinery to replicate and propagate the infection. Previous research has shown the potential of using Zika virus as an oncolytic agent in glioblastoma and neuroblastoma cell lines. The success of Zika-induced oncolysis in these cancers opens doors for expanding into other cancers, including NSCLC. Infection of six diverse NSCLC cell lines with ZIKV revealed that three cell lines were sensitive to ZIKV-induced oncolysis while the remaining were resistant. Transcriptome data analysis of TIM/TAM and CD24 mRNA expression levels were compared between ZIKV-sensitive and resistant cell lines, revealing AXL and TIM-1 as potential players in increasing or decreasing ZIKV infection. High AXL (TAM) expression correlated with increased sensitivity to ZIKV, while high TIM-1 (TIM) expression correlated with increased resistance. Experiments with AXL silencing in ZIKV-sensitive cell lines provided evidence of the role of AXL in increasing ZIKV sensitivity. Although further studies with TIM-1 must be done to determine its role in conferring resistance, AXL and TIM-1 have the potential to be biomarkers in predicting tumor sensitivity to ZIKV-induced oncolytic therapy.
| Identifer | oai:union.ndltd.org:ucf.edu/oai:stars.library.ucf.edu:hut2024-1032 |
| Date | 01 January 2024 |
| Creators | Somasekar, Shankari |
| Publisher | STARS |
| Source Sets | University of Central Florida |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Honors Undergraduate Theses |
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