Key Findings
Polyisoprenylated cysteinyl amide inhibitors (PCAIs) reduce viability, migration, and invasion of pancreatic cancer cells with KRAS mutations.
Lead compound NSL-YHJ-2-27 blocked over 90% of cell migration at 1 µM concentration.
PCAIs did not suppress MAPK and PI3K/AKT pathways but caused their hyperactivation, leading to oxidative stress, caspase activation, and apoptosis.
Transcriptomic analysis showed upregulation of tumor-suppressive genes and downregulation of metastasis-associated genes.
In 3D spheroid models, PCAIs induced disintegration and reduced invasion.
Background
Pancreatic ductal adenocarcinoma is often driven by KRAS mutations, limiting treatment options. PCAIs were designed to target oncogenic G-proteins broadly, unlike mutation-specific inhibitors.
Study Details
- Published in Oncotarget, Volume 17, June 3, 2026.
- First author: Kweku Ofosu-Asante; corresponding author: Nazarius S. Lamango, Florida A&M University.
- Experiments used pancreatic cancer cell lines with KRAS mutations.