MEPACRINE: A CANDIDATE CSPG4 TARGETED TREATMENT IN CANCER

Öz

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.

Anahtar Kelimeler

• Cancer
• CSPG4 gene
• in-silico
• Mepacrine

MEPAKRİN: KANSER TEDAVİSINDE CSPG4’Ü HEDEFLEYEN POTANSİYEL BİR TERAPÖTİK AJAN

Öz

Amaç: Bağışıklık sisteminin kansere karşı nasıl savaştığını anlamak, birçok kanser türünün tedavisinde umut verici sonuçlar gösteren devrim niteliğinde bir tedavi yöntemi olan immünoterapinin gelişimini büyük ölçüde etkilemiştir. İmmünoterapi, vücudun doğal savunma mekanizmalarını kullanarak ve bağışıklık hücrelerini uyararak, yabancı hücreleri, özellikle kanser hücrelerini, daha etkili bir şekilde tanıyıp ortadan kaldırmasını sağlamaktadır. Bu sırada, kemoterapi ve radyoterapi gibi geleneksel tedavi yöntemlerinin önemli yan etkilere neden olması ve tümöre özgüllükten yoksun olması nedeniyle, farklı kanser türlerinde immünoterapi ajanları alternatif tedavi seçenekleri olarak araştırılmaktadır. Geleneksel tedaviler sağlıklı dokulara zarar verebilmekte ve zamanla direnç gelişimine yol açabilmektedir; bu da, daha az yan etki ile daha yüksek etkinlik sunabilecek hedefe yönelik yaklaşımlara olan ihtiyacı gündeme getirmiştir. Gereç ve Yöntem: Bu çalışmada, Depmap’te yer alan 1129 kanserle ilişkili hücre hattında gerçekleştirilen PRISM canlılık testlerine dayanarak, CSPG4 genini hedefleyen bileşikleri belirlemek amacıyla Gene2Drug Pathway-Based Rational Drug Repositioning web sitesi kullanılarak in-silico (bilgisayar destekli) tarama yapılmıştır. Sonuç ve Tartışma: Toplam 438 bileşik, DepMap’te yer alan DRUG Sensitivity (PRISM Repurposing Primary) ve PRISM Repurposing Public 23Q2 araçları kullanılarak analiz edilmiştir. İlginç bir şekilde, fenazopiridin, amitriptilin, zuklopentiksol, mepakrin, lasalosid, verapamil ve aleksidin dahil olmak üzere toplam yedi bileşik anlamlı düzeyde duyarlılık göstermiştir (P < 1E-2). Ancak, mepakrin, 1129 kanserle ilişkili hücre hattı arasında CSPG4 hedefli tedavi adayı olarak en umut verici potansiyeli sergilemiştir. Bu in-silico (bilgisayar destekli) çalışma, kanser hücre hatlarında CSPG4 geninin mepakrin dahil birkaç bileşiğe duyarlı olduğunu ortaya koymuştur. Dolayısıyla, mepakrin ve CSPG4 hedefli tedavi stratejileri kanser tedavisinde umut vadetmektedir. Ancak, ilaç aracılı yolakların daha ayrıntılı olarak araştırılması için in vitro çalışmaların yapılması önerilmektedir.

Anahtar Kelimeler

• CSPG4 geni
• in-silico
• kanser
• Mepakrin

Kaynakça

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