Breakthrough: Spanish research team cures pancreatic cancer in mice using new triple therapy

Why Pancreatic Cancer Is So Difficult to Treat?

Pancreatic cancer is often detected at a late stage and spreads quickly. It is also highly resistant to existing treatments. Fewer than 10% of patients survive five years after diagnosis.

According to the International Agency for Research on Cancer (IARC), it ranks around twelfth in terms of new cases globally. However, the number of deaths is alarmingly close to the number of people diagnosed each year. In 2022, more than 500,000 people were newly diagnosed with pancreatic cancer worldwide, and nearly 470,000 lost their lives to the disease.

Also read- New Risk score help predict pancreatic cancer recurrance, finds study

The situation in India follows a similar pattern. The overall incidence rate is lower compared to many Western countries, ranging between about 0.2 and 2.4 cases per 100,000 people annually, depending on region and gender. However, because India has a very large population, even a low rate translates into tens of thousands of new cases every year.

At the heart of most pancreatic cancers lies a faulty gene called KRAS, which constantly sends signals telling cancer cells to grow and divide. KRAS mutations are found in over 90 per cent of pancreatic cancers. Although drugs that target KRAS have been developed in recent years, tumours often find new ways to survive, leading to relapse.

“Cancer is clever,” researchers noted, explaining that when one pathway is blocked, tumour cells activate alternative survival mechanisms.

Attacking Cancer from Three Angles

To prevent the tumour from adapting, the Spanish team designed a strategy that blocks three key pathways at the same time. 

As per India Today media report, the first drug, daraxonrasib, blocks the main KRAS signal that drives tumour growth. The second drug, afatinib, shuts down EGFR and HER2, pathways cancer cells often use to escape KRAS-targeted treatment. The third drug, SD36, disables STAT3, a backup system that helps cancer cells survive stress and resist therapy.

When all three drugs were used together in mice, the results were dramatic. The pancreatic tumours shrank completely and did not return, even more than 200 days after treatment stopped.

Equally important, the treatment was well tolerated. The animals did not show serious side effects. Based on the study results, the scientists are now considering moving toward clinical trials in humans with the therapy method.

In simple terms, the study shows that pancreatic cancer can be defeated by blocking its main engine, its escape routes, and its emergency backup system all at the same time. By doing so, the cancer is left with no way to adapt or fight back.

"The path to optimizing the triple combination therapy described here for use in a clinical setting will not be easy," a statement in the Proceedings of the National Academy of Sciences said. "(...) Despite current limitations, these results could open the door to new therapeutic options to improve the clinical outcome of patients with pancreatic ductal adenocarcinoma in the not-too-distant future," added the statement as reported by Detroit Free Press. 

Is It Ready For Humans?

Despite the promising results, scientists have warned that the therapy is still in the experimental stage. This preclinical result is promising but has not yet been tested in humans and is not a cure until it works on humans.

"The path to optimising the triple combination therapy for clinical use will not be easy," the authors noted in their publication. However, they added that the results open the door to designing new clinical trials aimed at improving survival in patients with pancreatic ductal adenocarcinoma.

If future human trials confirm these findings, the approach could mark a significant shift in the treatment of one of the world’s most lethal cancers. For now, the study offers a strong signal of hope, but more research is needed before the therapy can be tested in patients.

"These studies open a path to designing new combination therapies that can improve survival for patients with pancreatic ductal adenocarcinoma, the most common pancreatic cancer," the authors state in Proceedings of the National Academy of Sciences. "These results point the way for developing new clinical trials."

Public Reaction

The findings received mixed reactions from the public. While some have welcomed the study as a hopeful step forward, especially given how limited treatment options are available for pancreatic cancer, others have raised questions and concerns. 

Some pointed out that the therapy has only been tested in laboratory mice and not yet in human patients. They questioned how it could be described as a “cure” without clinical trials proving its safety and effectiveness in people.

Who is Dr Mariano Barbacid?

Dr Mariano Barbacid is a renowned Spanish molecular biologist and oncologist famous for pioneering cancer research, including the identification of the first human oncogene in 1982. He got his PhD in Madrid’s Universidad Complutense (1974) and trained as a postdoctoral fellow at the US National Cancer Institute (1974-78). 

In 1978, he started his own research group to study the molecular events responsible for the development of human tumours. His work led in 1982 to the isolation of the first human oncogene and the identification of the first mutation associated with the development of human cancer.