Drug repositioning breast cancer to help treat pancreatic cancer

The well-known drug, tamoxifen, could exploit weakness in physical "scaffolds" around tumors, according to a study by Imperial.

The report's authors, led by Imperial College London, claim that, as a result of new research, the drug could in future be re-used to help also treat pancreatic cancer.

For many years, tamoxifen has been used to treat a common form of bad cancer by preventing estrogen, which promotes the growth of bad tumors, reaching cancer cells and encouraging tumor growth. .

Now, a research team, led by Dr. Armando del Río Hernández of Imperial's Department of Bioengineering, has shown that in mice, tamoxifen helps to alter the physical environment, or "scaffolding" in which tumors develop. This scaffolding regulates the development of scar tissue, inflammation and immune responses, three key features of pancreatic cancer.

The researchers now want to explore whether this previously unseen effect could justify its use in most solid tumors, such as those seen in pancreatic cancer. Their findings are published today in EMBO Reports.

Scaffolding and oxygen

Pancreatic cancer has a very low survival rate, with less than 1% of people surviving for 10 years or more. Over the last 40 years, the survival rate has not changed significantly, and finding effective treatment is an urgent challenge for cancer researchers.

Most solid tumors, like those seen in pancreatic cancer, are surrounded by a large amount of connective tissue. The scar-like stiff tissue is presented as a scaffold around the tumor and prevents the delivery of the drug by preventing chemotherapy drugs from reaching the tumor. It also governs the growth and spread of tumors.

The formation of this connective tissue in pancreatic tumors is caused by stellate cells of the pancreas (PSC), which stiffen the tissue by applying physical forces and reshaping the architecture of the tissue.

The researchers examined this scaffold in mouse pancreatic tumors using a combination of biophysical methods and cancer biology. They discovered new insights into the interaction of cells surrounding pancreatic tumors and studied how tamoxifen alters the physical environment around these types of tumors.

The first article shows for the first time that tamoxifen inhibits the ability of CSPs to harden connective tissue surrounding tumors via a previously unknown mechanism, totally different from the known bad cancer pathway.

By preventing the tumor from stiffening in the tumor environment, tamoxifen regulates the immune response and slows down the invasion and spread of cancer cells.

For the second article, the researchers studied the role of oxygen in pancreatic cancer. Pancreatic tumor cells are exposed to very little oxygen, for which they have developed a protective mechanism: when oxygen levels drop, cells release molecules called hypoxia – induced factors. (HIF), which help cancer cells survive.

This article shows that tamoxifen mechanically inhibits the production of HIF, leaving cancer cells vulnerable to low levels of oxygen and more likely to die.

Dr. del Río Hernández, lead author of both articles, said: "Cancer research tends to study genetic influences on specific cancers, while our approach focuses on the physical factors that affect the environment. growth and spread of tumors. By studying the environment rather than the genes involved in cancer, we can reveal important traits common to all cancers and help identify broader treatments. "

The development of new drugs is expensive and takes several years. The authors say that the reutilization of an established cancer drug for a different tumor type might help effective treatments reach patients much faster and at lower cost.

However, they point out that, because their work has been conducted on cell cultures and mouse models, further research is needed before applying the drug to human patients.

Dr. del Río Hernández said, "We must first examine how the administration of tamoxifen alone or in combination with other chemotherapy drugs during long-term treatment affects the survival and spread of cancer. .

"Our work paves the way for more animal studies and perhaps human trials to explore the use of this well established drug to treat bad cancer. pancreas. The human trials usually take a lot of time and their results will determine if Tamoxifen can be used to treat pancreatic cancer and other solid tumors. "

The research was funded by the European Research Council and carried out in collaboration with researchers from Queen Mary University of London, the University of Osaka in Japan, the University Helsinki, Finland and the RIKEN Center for Integrative Medicine Science in Japan.

This article has been republished from materials provided by Imperial College London. Note: Content may have changed for length and content. For more information, please contact the cited source.