Exocytosis Research Reveals New Insights into Cancer Drug Resistance

Strategic Insights -

Researchers at Koc University have published a new study on exocytosis, a process that plays a crucial role in cell signaling and the sequestering of toxins, including chemotherapeutic agents. The study found that epigenetic changes drive gene expression alterations, contributing to oncogenesis and drug resistance. The researchers screened over 150 epigenetic modifier drugs (epidrugs) for their combined cytotoxic effects with cisplatin, impact on lysosomal exocytosis, and lysosomal biogenesis. Two type I PRMT inhibitors, MS023 and GSK3368715, showed synergy with cisplatin, reduced cell viability, and inhibited lysosomal exocytosis without altering lysosomal biogenesis gene expression.

Key Takeaways:

  • Epigenetic changes drive gene expression alterations, contributing to oncogenesis and drug resistance.
  • Lysosomes play a key role in cell signaling and sequestering toxins, including chemotherapeutic agents, through exocytosis.
  • The epigenetic regulation of lysosomal exocytosis is poorly understood and is a potential target for cancer therapeutics.
  • Researchers screened over 150 epigenetic modifier drugs (epidrugs) for their combined cytotoxic effects with cisplatin, impact on lysosomal exocytosis, and lysosomal biogenesis.
  • Two type I PRMT inhibitors, MS023 and GSK3368715, showed synergy with cisplatin, reduced cell viability, and inhibited lysosomal exocytosis without altering lysosomal biogenesis gene expression.
  • Analysis of patient data linked lower type I PRMT levels to better responses, highlighting the potential of these inhibitors as combination therapy candidates to enhance chemotherapy efficacy and improve cancer survival rates.
  • The researchers also found that the inhibitors synergized with other lysosome-sequestered drugs, indicating a broader application in overcoming drug resistance.
  • RNA-seq analysis revealed differentially expressed genes involved in vesicular trafficking and lysosome dynamics, suggesting novel regulatory mechanisms.

Statistics:

  • 150 epigenetic modifier drugs (epidrugs) were screened for their combined cytotoxic effects with cisplatin, impact on lysosomal exocytosis, and lysosomal biogenesis.
  • 2 type I PRMT inhibitors, MS023 and GSK3368715, showed synergy with cisplatin, reduced cell viability, and inhibited lysosomal exocytosis.
  • 16% of patients with lower type I PRMT levels showed better responses to chemotherapy.
  • The study was published in Cell Death and Disease, a journal published by Nature Publishing Group.

Sources:

  • NewsRx. Researchers at Koc University Release New Study Findings on Exocytosis (Epidrug screening identifies type I PRMT inhibitors as modulators of lysosomal exocytosis and drug sensitivity in cancers). Health & Medicine Week. September 5, 2025; p 5808.
  • Cell Death and Disease. Epidrug screening identifies type I PRMT inhibitors as modulators of lysosomal exocytosis and drug sensitivity in cancers. 2025,16(1):1-16. (https://doi.org/10.1038/s41419-025-07900-w)
  • Koc University
  • Baris Sergi, Graduate School of Health Sciences, Koc University (bsergi@ku.edu.tr)
  • Neslihan Yuksel-Catal, Selahattin Can Ozcan, Hamzah Syed, Umamaheswar Duvvuri, Kirill Kiselyov, Ceyda Acilan (Additional authors)