Pancreatic Cancer Treatment: New Hope from Organoid Research
Targeting cholesterol synthesis in pancreatic cancer: Coudl a heart drug hold the key? Groundbreaking research from Weill Cornell Medicine spotlights perhexiline maleate, a drug that inhibits cholesterol production, showing promise in suppressing the growth of pancreatic tumor organoids. Scientists screened over 6,000 compounds, pinpointing this heart medication to combat the aggressive nature of pancreatic cancer.The study reveals cholesterol’s key role, possibly opening new avenues for pancreatic cancer treatment. News Directory 3 highlights this critical advancement in cancer research. Learn how this discovery could revolutionize future therapies, offering hope for better outcomes. Discover what’s next …
Heart Drug Shows Promise Targeting Pancreatic Cancer’s Cholesterol Role
Updated June 15, 2025
A new study from Weill Cornell Medicine suggests a potential new avenue for pancreatic cancer treatment. Researchers have identified that targeting cholesterol synthesis, a key vulnerability in pancreatic cancer cells, could play a notable role in future therapies.
The study,published in Cell Stem Cell,detailed how scientists used lab-grown tissues called organoids to model cancers. They screened over 6,000 compounds on pancreatic tumor organoids, each containing a common pancreatic cancer-driving mutation. The screening process revealed that perhexiline maleate, a drug already used to treat heart conditions, effectively suppressed the growth of these organoids.
The team discovered that the cancer-driving mutation forces an abnormally high production of cholesterol, a process the drug largely reverses. This finding highlights the potential of targeting cholesterol synthesis in treating pancreatic cancer.
Dr. Todd Evans, co-senior author and vice chair for research in surgery at Weill Cornell Medicine, said the findings identify hyperactive cholesterol synthesis as a vulnerability that may be targetable in most pancreatic cancers.
Dr.Shuibing Chen, also a co-senior author and director of the center for Genomic Health, emphasized the value of using genetically well-defined organoids to model cancer and discover new treatment strategies.
The organoid-based screening system allowed researchers to test various compounds,including FDA-approved drugs,on organoids engineered to contain mutations known to drive human pancreatic tumors. All organoids contained KrasG12D, a mutant gene found in most cases of pancreatic ductal adenocarcinoma (PDAC), a notably lethal form of cancer.
Perhexiline maleate proved to be the most effective,blocking growth in all KrasG12D-containing organoids and even destroying some within days. This occurred without harming healthy organoids lacking the mutation. The drug also showed similar effects on mouse and human PDAC-derived tumor organoids transplanted into mice.
Further analysis revealed that the cancer-associated mutant kras considerably boosts cholesterol production in organoid cells. Perhexiline maleate counteracts this effect by inhibiting SREBP2, a key regulatory factor in the cholesterol metabolic pathway.
The revelation of cholesterol’s role aligns with existing knowledge of its importance in cell building and survival,suggesting that targeting it could be an effective strategy against PDAC and other KRAS-mutant cancers.
Evans hopes their cholesterol-targeting strategy will be independent of particular KRAS mutations, making it difficult for tumors to develop resistance.
while perhexiline maleate itself is unlikely to be used directly for PDAC treatment due to potential side effects, including liver and nerve damage, researchers aim to develop a safer and more potent compound.
Chen said they want a better compound for cancer treatment,noting the drug’s simple chemical structure suggests it can be modified to improve its properties.
What’s next
The research team plans to use perhexiline maleate as a foundation for developing a refined drug candidate for PDAC and as a tool for studying cholesterol synthesis in various cancers.