UNMC researchers to study lung cancer brain metastases

UNMC researchers have received a four-year, $710,000 grant from the Department of Veterans Affairs to study why some patients with lung cancer develop brain metastases.

Lung cancer is the leading cause of cancer-related mortality in the world, accounting for about 24% of cancer-related deaths in both women and men. The predicted five-year survival rate of one type of lung cancer — non-small-cell lung cancer — is 21%, said Apar Ganti, MD, principal investigator of the study and oncologist specializing in lung cancer at UNMC and the Nebraska Western Iowa VA Medical Center in Omaha.

Once cancer has spread to the brain, the outcomes are poor as most chemotherapy drugs cannot penetrate into the brain in high enough concentrations to be effective, he said.

“There is an urgent need to discover new biomarkers and specific directed therapeutic strategies for this central nervous system metastasis,” Dr. Ganti said. “The majority of patients with non-small-cell lung cancer present at advanced incurable stages where systemic therapy is the mainstay of treatment.

“We have found that a mucin — a protein — mucin 5AC (MUC5AC) — is seen in high levels in the lung tumors of patients whose brain lesion has been removed due to spread. We believe that this protein somehow promotes the spread of cancer into the brain,” Dr. Ganti said. “If we are able to prove our hypotheses, we hope to be able to target this protein — mucin 5AC — and thereby potentially prevent the spread of lung cancer to the brain.”

Mucins are major components in mucus that function as a physical barrier.

Dr. Ganti and UNMC collaborators (Mohd Wasim Nasser, PhD, Imayavaramban Lakshmanan, PhD, and Surinder Batra, PhD) will try to identify the mechanism by which the protein stimulates the spread of lung cancer to the brain.

“We hope that we will be able to identify the pathways by which non-small cell lung cancer spreads to the brain. Since this is a common site of spread of lung cancer, this will impact a large number of patients. If we can prove this, the next step will be to study patients with lung cancer and brain metastases,” Dr. Ganti said.

The team will use lung cancer cells and lung cancer animal models to decrease the MUC5AC protein level and evaluate the spread of lung cancer to the brain. They also will try and identify other proteins that may act as intermediate steps in this process.

Finally, he said they also would define the clinical utility of MUC5AC antibodies currently being developed at UNMC (Maneesh Jain, PhD, Grish Varshney, PhD, and Sukhwinder Kaur, PhD) on preventing/treating metastases in patients for the first time.