Today, improved drug treatments provide many cancer patients longer lives, and in many instances, these therapeutics knock down cancer cells at their point of origin.

But something else is happening, too: researchers are seeing these cancer cells change, adapt and migrate to the brain, where treatment options are limited and the disease is almost always fatal.

TGen Associate Investigator Dr. Nhan Tran leads a nationwide research team studying how to stop breast cancer cells from invading the brain.

“This will open up a huge research arena at TGen,’’ said Dr. Tran, who is co-heading the Breast Cancer/Central Nervous System Metastasis (CNS Mets) Project, which eventually could affect all aspects of TGen cancer research.

A central goal of the project is to identify cellular pathways, biomarkers and other key molecular mechanisms that will help scientists find ways to prevent this type of cancer — CNS Mets — from entering the brain.

“The translational component will be fast and real. We’re going to start pointing our clinical partners in a more focused direction,’’ said Dr. Tran.

Researchers in clinical trials are finding new drug treatments that are successfully shrinking tumors, allowing cancer patients to live longer, healthier lives. The downside, however, is that as patients live longer — sometimes years — their cancers often invade other parts of the body. When cancer invades the brain, doctors have few options.

Current chemotherapeutic regimens, often applied intravenously, have little impact on the course of CNS Mets, in part because of the blood-brain barrier, the separation of circulating blood from the cerebrospinal fluid.

And cancers that migrate to the brain often erupt in multiple sites, making it almost impossible to remove them by surgery or radiation, or even a combination of both.

“This project has huge implications for patients in clinical trials,” said Dr. Tara Iyengar, a co-Principal Investigator on the study with Dr. Tran and a Drug Development Scholar at TGen Clinical Research Services (TCRS) at Scottsdale Healthcare, where more than 30 clinical trials are underway. TCRS, at the Virginia G. Piper Cancer Center, is a partnership of TGen and Scottsdale Healthcare.

“Brain metastases, in general, are an under-funded area of research. Most clinical-trial protocols will not allow patients with brain metastases; the few that do have strict requirements about radiation treatment and steroid support. This makes it very difficult for a large population of patients to receive new innovative drugs,” said Dr. Iyengar, a board certified physician in hematology oncology, specializing in brain tumors.

“If we can highlight pathways that drive these metastases, we could potentially find drugs that could inhibit further growth,” said Dr. Iyengar. “This would have a major impact on survival. We have made great strides in controlling systemic disease. But if we can’t control CNS Mets, the patient succumbs to this disease.”

This study, one of nearly 30 funded by an Integration Grant Program resulting from the recent alliance and affiliation between TGen and the Van Andel Research Institute, pairs a TGen scientist with a VARI scientist as a way to accelerate the research at both institutions, as well as leverage subsequent grants, mainly from the National Institutes of Health. The project also received funding from the Bruce T. Halle Family Foundation, and from the C.A.R.E. group at Desert Mountain.

Dr. James Resau, a project co-investigator and Senior Investigator at VARI, is providing validation research for this CNS Mets study.

“It is our hope that we would be able to objectively determine numbers and variations of labeled cells that metastasize to the brain, and document how genetic manipulations and environmental/therapeutic interventions affect their growth and pathology,” Dr. Resau said.

Other key project researchers are Dr. John Carpten, a project co-investigator and Director of TGen’s Integrated Cancer Genomics Division, and Dr. Bodour Salhia, a TGen breast cancer researcher.

TGen researchers have enlisted the help of hospitals at the University of Iowa and University of Toronto, which are providing tumor samples for TGen analysis.

“We’re going to have a comprehensive genomic analysis of all of the samples,’’ Dr. Tran said. “That will allow us to dive into understanding the cellular pathways that are unique to driving brain metastasis, and whether those pathways are targetable. Are there drugs out there currently available to target this particular pathway?”

TGen’s clinical partners should then be able to enroll patients, and immediately apply drugs already approved for treating other cancers to patients who have brain metastases, Dr. Tran said. Ongoing studies could also result in new drugs that could prevent CNS Mets from ever entering the brain.

Dr. Tran predicts that eventually the findings will be applied to other cancers, including lung, pancreatic, colon and renal cancers.

“It’s a very interesting and unique study,” Dr. Tran said. “Our hope is that we can have a very clear impact now, and a sustained clinical impact in the future.’’