Starving Lung Cancer Tumors May Limit Growth

Blocking the recruitment of blood vessels suppresses small cell lung cancer tumor growth.

A new approach for treating small cell lung cancer has the potential to slow down tumor growth, a recent study indicates.

Although small cell lung cancer is mostly exclusive to smokers, it is an aggressive form of cancer where 98% of people diagnosed with stage 4 will die in less than 5 years.

Nicotine is found to help accelerate the progression of lung cancer by helping the tumor to recruit blood vessels. Nicotine binds to the protein alpha7-nicotinic receptor located on the surface of cancer cells, increasing the blood supply.

“Nicotine is not a carcinogen -- it doesn't cause cancer -- but once the cancerous process is initiated, nicotine helps the cancer cells to grow and survive,” said researcher Zachary Robateau. “If you can block that process, you could potentially suppress the growth of these small cell lung cancer cells.”

The current study looked to starve the cells of the blood supply to inhibit growth.

“The main challenge of small cell lung cancer is that patients initially respond well to chemotherapy, but the tumor inevitably relapses within a short while, and after relapse it no longer responds to chemotherapy or radiation,” said senior study author Piyali Dasgupta, PhD. “Our hope is that the therapies we're investigating could combine with chemotherapy to delay that relapse and improve patient outcomes.”

During an initial proof-of-concept study, researchers used a blocker of nicotine-al-pha7-nAChR interaction called MG624. The results of the study showed that MG624 was able to block the recruitment of blood vessels and suppress tumor growth in mice.

Now researchers are testing whether the compound Memanitine, an FDA-approved drug for the treatment of mild-to-moderate Alzheimer’s disease and dementia could have similar effects.

“A lot of the appeal of Memanitine, in particular, is that it's already used in the clinic and is well tolerated by patients” Dasgupta said. "If Memanitine blocks the blood supply to small cell lung cancers, then it may be beneficial in conjunction with chemotherapy in patients. Plus, the bench-to-bedside process may be quicker since the drug is already in clinical use.”

Researchers believe that the combination of Memanitine or MG624 in combination with chemotherapy could help delay a tumor’s relapse. The next step is to test Memanitine in mouse models with human small cell lung cancer cells.