New Therapy Shows Promise for Pancreatic Cancer Treatment

A recent study has revealed that a combination of three drugs may offer hope in the fight against pancreatic cancer, a disease known for its low survival rates.

Pancreatic cancer is classified as one of the deadliest types of cancer, with a five-year relative survival rate around 13%. This means that a staggering 87% of those diagnosed are unlikely to survive past five years. For patients diagnosed at advanced stages, the survival rate dips even lower, sometimes to about 1%.

In a study published on December 2 in PNAS, researchers explored a new therapy that targets three key pathways contributing to cancer growth. Early tests in mice have shown encouraging results.

According to the authors, “These studies pave the way for creating new combination therapies that could enhance survival for patients with pancreatic ductal adenocarcinoma,” the most prevalent form of the disease. They pointed out that these findings could inform future clinical trials.

The challenge with pancreatic cancer is that it tends to develop quietly, often going unnoticed until it’s progressed significantly and spread to other organs, complicating surgical removal.

Current standard treatments, like chemotherapy, aim to attack rapidly dividing cells but frequently cause significant damage to healthy tissues. Even then, tumors find ways to evade treatment and continue growing.

This new method not only inhibited the regrowth of cancer in the test subjects but also did so without any noticeable toxic effects.

Almost all pancreatic cancers are linked to a mutation in a gene known as “KRAS,” which is essential for regulating cell division and growth. When this gene is mutated, it can lead to unchecked cell division and cancer. Prior efforts to combat this issue, led by Carmen Guerra, involved studying how these mutations allow tumors to thrive. She found that while cutting off certain growth pathways could slow small tumors, larger ones could often adapt and survive by finding alternative pathways.

In their recent work, Guerra’s team identified that a protein called STAT3 becomes overactive when other growth routes are disrupted, suggesting it’s a backup pathway for tumor growth.

The researchers then tested a genetic block of this pathway along with other principal tumor growth drivers, leading to tumor regression, which further confirmed the importance of STAT3 as a “mechanism of resistance.”

They proceeded to translate this strategy into a drug-based approach, employing a combination of two established drugs—afatinib, approved for specific lung cancers, and daraxonrasib, still in clinical trials. The third medicament targets STAT3 directly.

The combination therapy was trialed in different mouse models: one where cancer cells were implanted in the pancreas, another involving genetically modified mice prone to pancreatic cancer, and a third using human tumor samples. Remarkably, the treatment led to complete tumor elimination in all models studied.

“It was hard to even spot where the tumor had been,” Guerra noted. “The pancreas looked entirely normal.”

Furthermore, the therapy appeared to prevent future resistance, with tumors not returning for at least 200 days, a significantly longer duration than what is typically observed with single-drug therapies.

Crucially, the triple-drug approach did not produce severe side effects in the tested mice. They maintained similar weight, blood counts, and organ health compared to those receiving placebo treatments.

However, while these findings are promising, the research was conducted in mice, and there may be differences when it comes to human cancer patients. Guerra mentioned that while the mice seemed more resistant to potential toxicity, some of the drugs, such as afatinib, have known side effects in humans, including skin and gastrointestinal issues.

The research team is now focused on identifying alternatives and creating better therapies targeting the same pathways.

Guerra also emphasized that pancreatic tumors can be genetically diverse, with each patient’s tumors presenting different alterations. To address this, they plan to explore additional mouse models carrying various KRAS mutations and other genetic changes related to cancer, aiming to test the therapy’s effectiveness across a wider range of tumors.