Researchers from Northwestern Medicine have discovered that a new combination of drugs may help fight pancreatic cancer, a disease known for being hard to treat.
Their study, published in the journal Cancer Research, found that combining two drugs—MRTX1133 and venetoclax—caused tumors to shrink in mice, offering hope for better treatment options.
Pancreatic cancer is the third most common cancer in the U.S., with over 66,000 new cases expected this year.
Unfortunately, the survival rate for pancreatic cancer remains very low, with only about 13% of patients living for five years after diagnosis.
Current treatments, including surgery, chemotherapy, and radiation, have not significantly improved these survival rates. This has led scientists to search for new, more effective therapies.
One major target in pancreatic cancer is the KRAS gene, which is mutated in over 90% of cases. The KRASG12D mutation, in particular, is present in about half of pancreatic cancer patients, making it a key focus for researchers. MRTX1133, a drug that targets KRAS, has shown potential, but its effects are not always long-lasting, and tumors can develop resistance.
Dr. Hidayatullah G. Munshi, the senior author of the study, explained that KRAS inhibitors like MRTX1133 are a new and promising area of research.
However, they are not enough on their own because cancer cells find ways to resist the drug over time. To overcome this, the team looked for ways to strengthen MRTX1133’s effects.
The researchers used 3D cultures that mimic the environment of pancreatic tumors.
When they treated these cultures with MRTX1133, they noticed that while the drug increased levels of a protein called BIM, which should cause cancer cells to die, the tumors continued to grow.
This happens because cancer cells have mechanisms that block cell death, even when BIM levels rise.
To tip the balance in favor of killing the cancer cells, the scientists added venetoclax, a drug already approved by the FDA to treat blood cancers. They found that venetoclax worked with MRTX1133 to increase cancer cell death and shrink tumors, even in cases where the cancer had become resistant to MRTX1133 alone.
These findings suggest that combining venetoclax with KRAS inhibitors could be a more effective treatment for pancreatic cancer. The next step is to test this combination in clinical trials with pancreatic cancer patients.
Researchers hope that this new approach can improve treatment results, either by using it early in the treatment process or to re-sensitize tumors that have stopped responding to KRAS inhibitors.
