PEG-BCT-100 and Canavanine Synergistically Induce Apoptosis in Arginine Biosynthetic Enzyme-Deficient Pancreatic Cancer

Cancer Res Commun. 2024 Dec 1;4(12):3180-3189. doi: 10.1158/2767-9764.CRC-24-0425.

Abstract

This study investigates the synergistic antitumor effect of PEG-BCT-100, an arginase, in clinical trials, with canavanine in pancreatic cancer, in vitro and in vivo. The treatment induces cancer cell apoptosis while sparing normal fibroblasts. Our findings suggest heightened susceptibility of pancreatic tumors deficient in arginine biosynthesis enzymes ASS1 and OTC.

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Arginase / metabolism
  • Arginine* / pharmacology
  • Argininosuccinate Synthase / genetics
  • Argininosuccinate Synthase / metabolism
  • Canavanine* / pharmacology
  • Cell Line, Tumor
  • Drug Synergism*
  • Humans
  • Mice
  • Ornithine Carbamoyltransferase / genetics
  • Ornithine Carbamoyltransferase / metabolism
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / pathology
  • Polyethylene Glycols / pharmacology
  • Xenograft Model Antitumor Assays

Substances

  • Arginine
  • Canavanine
  • Arginase
  • Polyethylene Glycols
  • Argininosuccinate Synthase
  • Ornithine Carbamoyltransferase