Lung cancer is the most common cause of cancer-related death, annually causing over 160,000 deaths in the US and over a million deaths world wide. Treated by surgery and chemotherapy, it is also one of the most intractable, with a 5 year survival rate of 14%.

In November, researchers funded by SWCRF published a paper in the Journal of the National Cancer Institute about a breakthrough in understanding the cell malfunctions that lead to lung cancer, opening a new genetic path to combating it.

The team led by Reuben Lotan of M.D. Anderson Cancer Center proved that the GPRC5A protein is an effective check on the development of lung cancer.

• 78% of mice bred to “knockout” the gene that produces the anti-tumor protein GPRC5A developed pre-cancerous lesions in comparison to only 10% of normal mice who developed such lesions.
• To determine whether GPRC5A protein had the same effect in humans, the investigators compared human lung tumors and nearby tissue. In 61% of samples studied, the tumors showed a significantly lower level of GPRC5A than the healthy surrounding tissue.
• The team re-analyzed genetic data published in other studies and found a lower level of the GPRC5A protein in lung tumor tissue than in normal lung tissue.
• The researchers inserted the GPRC5A gene back into lung cancer cell lines in a laboratory experiment, which inhibited the growth of human lung cancer cells by 91%.

Thus, these several methods confirmed that the GPRC5A anti-tumor protein plays an important role in controlling lung cancer growth.

The mice were bred to eliminate the gene that produces GPRC5A. Humans with lung cancer have the GPRC5A gene, but nonetheless have a deceased capacity to make the protective protein. In other research funded by the Samuel Waxman Cancer Research Foundation, it was demonstrated that certain compounds can increase production of GPRC5A protein

This work opens a new path in treating lung cancer – the possibility of finding a precisely targeted genetic agent that will enhance production of the protective GPCRA5 protein. This would effectively combat the cancer without difficult side effects for the patient.
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