The Assessment of the Effect of Autophagy Inhibitors—Chloroquine and 3-Methyladenine on the Antitumor Activity of Trametinib Against Amelanotic Melanoma Cells DOI Creative Commons
Dominika Stencel, Justyna Kowalska, Zuzanna Rzepka

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(7), P. 557 - 557

Published: April 7, 2025

Malignant melanoma, particularly amelanotic contributes to a very serious problem in public health. One way find new therapies is learn about and understand the molecular pathways that regulate cancer growth development. In case of tumor, autophagy process can lead development or inhibition cancer. This study aimed assess cytotoxicity connection trametinib (MEK1 MEK2 kinase inhibitor) with inhibitors—chloroquine (lysosomal clearance autophagosomes 3-methyladenine (phosphatidylinositol 3-kinases inhibitor), on two melanoma cell lines (C32 A-375). The results showed combination therapy had better anti-proliferative effects than alone both lines. C32 line was more sensitive treatment (alone combinations), A375 sensitivity chloroquine combinations). effect accompanied by dysregulation cycle, decrease reduced thiols, depolarization mitochondrial membrane level p44/p42 MAPK. Both inhibitors have ability induce apoptosis. Differences LC3A/B LC3B proteins between samples indicate these drugs inhibit at different stages. enhancement suggests possibility combining anti-cancer potential modulators process.

Language: Английский

Emerging RAS Inhibitors: Heterocyclic and Spirocyclic Compounds in Cancer Therapeutics DOI Creative Commons
Robert B. Kargbo

ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: 16(2), P. 216 - 218

Published: Jan. 29, 2025

Researchers have long recognized RAS mutations as one of the most challenging targets in oncology. These genetic alterations are central drivers tumor progression cancers such melanoma, colorectal cancer, and pancreatic adenocarcinoma. The recent advancements described patent applications WO 2024/243186 A2 2024/246099 A1 introduce two novel classes inhibitors: heterocyclic compounds targeting NRAS G12D spirocyclic derivatives directed at KRAS mutations, including G12C, G12D, G12 V. compounds, a fresh innovative approach, disrupt critical RAS-dependent signaling pathways, offering pathway to mitigate growth overcome resistance standard therapies. This Patent Highlight explores their mechanisms, preclinical successes, implications for future cancer treatment strategies.

Language: Английский

Citations

0
Amelanotic Melanoma: Diagnostic Challenges, Treatment Innovations, and the Emerging Role of AI in Early Detection DOI Creative Commons
Diala Ra’Ed Kamal Kakish, Jehad Feras AlSamhori, Ahmad Ayman

et al.

Journal of Medicine Surgery and Public Health, Journal Year: 2025, Volume and Issue: unknown, P. 100189 - 100189

Published: March 1, 2025

Language: Английский

Citations

0
The Assessment of the Effect of Autophagy Inhibitors—Chloroquine and 3-Methyladenine on the Antitumor Activity of Trametinib Against Amelanotic Melanoma Cells DOI Creative Commons
Dominika Stencel, Justyna Kowalska, Zuzanna Rzepka

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(7), P. 557 - 557

Published: April 7, 2025

Malignant melanoma, particularly amelanotic contributes to a very serious problem in public health. One way find new therapies is learn about and understand the molecular pathways that regulate cancer growth development. In case of tumor, autophagy process can lead development or inhibition cancer. This study aimed assess cytotoxicity connection trametinib (MEK1 MEK2 kinase inhibitor) with inhibitors—chloroquine (lysosomal clearance autophagosomes 3-methyladenine (phosphatidylinositol 3-kinases inhibitor), on two melanoma cell lines (C32 A-375). The results showed combination therapy had better anti-proliferative effects than alone both lines. C32 line was more sensitive treatment (alone combinations), A375 sensitivity chloroquine combinations). effect accompanied by dysregulation cycle, decrease reduced thiols, depolarization mitochondrial membrane level p44/p42 MAPK. Both inhibitors have ability induce apoptosis. Differences LC3A/B LC3B proteins between samples indicate these drugs inhibit at different stages. enhancement suggests possibility combining anti-cancer potential modulators process.

Language: Английский

Citations

0