Scientists at Roswell Park Comprehensive Cancer Center, Buffalo, New York, have discovered a small molecule that kills pancreatic cancer cells, according to Medical Xpress.
They found that the molecule inhibits the growth and metastasis of pancreatic cancer cells via the iron metabolism pathway. This finding could help develop a new drug candidate for treating pancreatic cancer.
The researchers published their findings in the journal Molecular Cancer Therapeutics.
The molecule, MMRi62, inhibits metastasis in pancreatic cancer through degradation of ferritin heavy chain and mutant p53. It targets iron metabolism to kill cancer cells as well as the harmful proteins that encourage their growth and spread.
This molecule could be further developed and refined to a new type of pancreatic cancer therapy.
Dr. Xinjiang Wang said, “MMRi62 causes degradation of an iron-storage protein called FTH1, as well as a protein that is mutated in PDAC, resulting [in] inhibition of metastasis and ferroptosis, a form of cell death triggered by free cellular iron.”
Pancreatic ductal adenocarcinoma (PDAC) cells are more susceptible to ferroptosis. PDAC is one of the highly aggressive lethal malignancies.
The discovery of new drug candidates that activate ferroptosis represents a new area of potential therapies for PDAC, which accounts for 90% of all types of pancreatic cancer.
PDAC is associated with mutations in the KRAS and TP53 genes, which drive the disease and make tumors resistant to chemotherapy. There are no drugs or treatments targeting these mutations so therapeutic options for PDAC are limited. The disease has a 5-year survival rate of only 12%.
Dr. Wang said, “We showed through this study that in a preclinical model, MMRi62 is capable of inducing ferroptosis in PDAC cells harboring either KRAS or TP53 mutations, which in turn inhibited tumor growth and prevented metastasis of tumors to distant organs.”
“Although no ferroptosis-inducing agents are currently available,” he added, “our hope is that our discovery will lead to promising new MMRi62-based treatments for recalcitrant cancers such as PDAC.” The article was published in Medical Xpress.
