KRAS amplification fuels resistance to a RAS(ON) inhibitor in pancreatic cancer, guiding combo therapies
TL;DR
In pancreatic ductal adenocarcinoma, resistance to the RAS(ON) inhibitor daraxonrasib emerges in about 59% of patients, driven mainly by acquired KRAS amplification and alterations in RTK/MAPK/PI3K pathways, with no therapy‑emergent secondary KRAS mutations observed. Preclinical models validate these resistance mechanisms and show that combining daraxonrasib with RTK inhibitors, DDR-targeting agents, or the mutant KRAS G12D inhibitor zoldonrasib can prevent resistance, informing rational combination strategies for PDAC.
Topics:healthscience#acquired-resistance#combination-therapy#kras-amplification#pancreatic-cancer#ras-on-inhibitors#science
- Acquired resistance to the RAS(ON) multi-selective inhibitor daraxonrasib guides rational combination therapy strategies in pancreatic cancer Nature
- Pancreatic Cancer Specialists Getting a Jump on Daraxonrasib Medscape
- Patients in Illinois starting to receive experimental pancreatic cancer drug: ‘Game changer’ Chicago Tribune
- Stanford expands access to revolutionary pancreatic cancer drug Stanford Medicine
- Intermountain Health Oncologists Say New Drug to Treat Pancreatic Cancer May Be a “Game Changer” as 10 Intermountain Hospitals Join National Initiative Intermountain Health
Want the full story? Read the original reporting
Read on Nature