Overcoming resistance in pancreatic cancer treatment
Researchers have developed a new
cocktail of drugs that shrink pancreatic tumours in mice by blocking pathways
that cancer cells use.
Researchers at Cold Spring Harbor
Laboratory (CSHL), US have found a way to tackle the problem of cancer cells
developing resistance to drugs and stop the growth of pancreatic tumours in
mice.
Professor David Tuveson’s lab at
CSHL is focused on identifying better treatment strategies to help prolong
survival for patients with pancreatic cancer, including new drugs that can be
introduced into clinical trials.
More than 90 percent of
pancreatic cancer patients carry a mutation in the cancer-causing gene KRAS.
The KRAS oncogene is difficult to drug directly, so researchers are testing
indirect routes to shutting it down. One approach targets the AKT and
MAP-Kinase (MAPK) downstream signalling pathways that support KRAS.
“Some clinical trials have
targeted these pathways, but high toxicity levels and therapeutic resistance
development precluded further investigation of these regimens,†said Youngkyu
Park, a Research Investigator in the Tuveson lab. “Toxicity can occur when
anti-tumour agents aren’t malignancy-specific. That means they risk killing
healthy cells as well.â€
The Tuveson lab encountered the
problem of resistance pathways when it tried to barricade the AKT and MAPK
pathways in PDA. So, to develop an effective cancer drug, they created drug
cocktails that block both the main pathways supporting pancreatic cancer cell
growth and cancer cell-specific resistance pathways.
By culturing normal human cells and cancer cells in three-dimensional (3D) organoid models and testing them concurrently, the team was able to distinguish particular signalling mechanisms that only affected pancreatic cancer cells. This allowed them to pinpoint the ERBB signalling pathway as the pancreatic cancer-specific resistance mechanism following AKT/MAPK blockade.
By inhibiting ERBB signalling in
addition to MAPK signalling, the researchers observed pancreatic tumours shrink
in organoid mouse model of pancreatic ductal adenocarcinoma (PDA).
From source: https://www.drugtargetreview.com/news/48676/overcoming-resistance-pancreatic-cancer/
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