MEPACRINE: A CANDIDATE CSPG4 TARGETED TREATMENT IN CANCER

Objective: Understanding how the immune system fights cancer has greatly influenced the conception of immunotherapy, a revolutionary form of cancer treatment that has demonstrated encouraging outcomes in the treatment of many cancers. It enables the body to identify and eliminate foreign cells, such as cancer cells, more efficiently by utilizing the body's inherent defense mechanisms and stimulating immune cells. Meanwhile, immunotherapy agents are being explored across various cancer types as an alternative due to the limitations of conventional treatments like chemotherapy and radiation, which often cause significant side effects and lack tumor specificity. These traditional therapies can damage healthy tissues and lead to resistance over time, prompting the search for more targeted approaches that offer improved efficacy with fewer adverse effects. Material and Method: In-silico screening using the Gene2Drug Pathway-Based Rational Drug Repositioning website was employed to identify compounds targeting the CSPG4 Gene, based on PRISM viability assays performed on 1129 cancer-related cell lines in Depmap. Result and Discussion: A total of 438 compounds were analyzed using DRUG Sensitivity (PRISM Repurposing Primary) and PRISM Repurposing Public 23Q2 Tool in DepMap. Interestingly, a total of seven compounds, including phenazopyridine, amitriptyline, zuclopenthixol, mepacrine, lasalocid, verapamil, and alexidine, were significantly sensitive (P < 1E-2). Yet, mepacrine showed the most promising potential as a CSPG4-targeted treatment candidate across 1129 cancer-related cell lines. This in silico study showed that the CSPG4 gene's sensitive to several compounds in cancer cell lines, including mepacrine. Therefore, holding promise for mepacrine- and CSPG4-targeted treatment strategies in cancer. However, it is recommended to further investigate the drug-mediated pathways through in vitro studies.