In a recent study, Yale researchers discovered a mechanism co-opted by lung cancer cells in order to spread to the brain.

Lung cancer is the No. 1 cause of cancer-related deaths, killing more people than breast, colon and prostate cancers worldwide, according to Don Nguyen, a professor of pathology at the Yale School of Medicine and a senior author of the study. The most frequentluy diagnosed form of lung cancer is lung adenocarcinoma, which originates in the lungs but is most dangerous after it has migrated to other parts of the body in a process known as metastasis. LUAD metastasis to the brain is often deadly and can leave survivors with heightened risk of relapse and a far lower quality of life, Nguyen said.

Metastasis is one of cancer’s many “black boxes” Nguyen said, in that very little is known about the mechanisms that allow this process to take place.

“Simply put, if we can understand the mechanisms of how lung cancer spreads, we can block them,” said Roy Herbst ’84, chief of medical oncology at the Yale Cancer Center and a co-author of the study.

Prior to the researchers’ study, it was unclear how the LUAD cancer cells, which are used to the environment of the lungs, could survive in the hostile environment of the central nervous system, Nguyen said. The researchers studied the tumors of LUAD patients and discovered a correlation between over-expression of the extra-cellular matrix interacting molecule HMMR and high propensity for metastasis, according to Laura Stevens GRD ’17, a first author of the study.

Extracellular molecules regulate signaling events between tumor cells and their environment and establish tissue architecture, Nguyen said. He added that the tumor cells that can interact with these extracellular molecules have an advantage when it comes to surviving in the brain.

“The extracellular molecule we studied is involved in inflammation and repair,” Nguyen added. “The tumor cells take advantage of that mechanism for their own purposes.”

The discovery has major implications for the treatment of various cancers, Herbst said. Cancer cells rely on pathways, like the one Nguyen’s lab discovered, to survive in the organs into which they metastasize. Inhibiting these pathways decreases the chance of cancer thriving in the foreign organs, thereby reducing the threat to the patient.

A drug that aims to do just that is currently in the clinical trial phase. At the moment, cancer therapy is largely focused on attacking the cancer itself. The researchers hope that future treatment will incorporate drugs that inhibit the pro-survival mechanisms cancer utilizes, Stevens added.

The research is part of a larger ongoing Yale effort to understand and treat cancer more effectively, thanks to a major grant called the Specialized Programs of Research Excellence. One goal of this project is to bring together the research done in the lab and the applications of that work in the clinic, Herbst said.

While this study focused specifically on lung cancer metastasizing into the brain, there are other mechanisms that assist the spread of other cancers to other organs that are yet to be discovered.

“We’re not just targeting the cancer cells anymore,” Stevens said. “We’re using the environment around the cancer to try and inhibit cancer progression.”

A man stands a one in 14 chance of developing lung cancer in his lifetime, according to the American Cancer Society. For women, that figure is one in 17.