A team led by a scientist from Scripps Florida has identified a protein linked to higher rates of survival in patients with head, neck and non-small cell lung cancer, including patients who have not received chemotherapy – a treatment associated with toxic side effects. The discovery could help scientists develop new diagnostics and therapies and help physicians determine the best long-term treatments for patients with these cancers.
The findings focus on a protein called Choline phosphate cytidylyltransferase-α CCT-α or CCTα, an “antigen” that prompts the immune system to produce antibodies against it.
TSRI Associate Professor Laura Niedernhofer
“Based on what we found, a high CCTα expression appears to be indicative of survival, making CCTα a promising biomarker,” said Laura Niedernhofer, a TSRI associate professor who led the study with Gerold Bepler of the Karmanos Cancer Institute. “Our findings suggest that CCTα may, in fact, be more important in determining outcomes in patients with both types of cancer than the already established ERCC1.”
The new study turns previous studies on ERCC1 on their heads. Dozens of large clinical trials are being conducted using the ERCC1 DNA-repair protein as a determinant of whether patients with lung, pancreatic, gastric, colorectal, esophageal or ovarian cancer should be treated with platinum-based chemotherapy drugs, a very potent but toxic DNA-damaging agent.
However, the new research suggests that these positive results were not actually due to ERCC1, but to CCTα—which also binds to the antibody most frequently used to measure ERCC1 expression.
“Our results show CCTα may be a better predictor of patient outcomes than expression of ERCC1,” said Dr. Niedernhofer.
The new results were based on an examination of samples from 187 patients with non-small cell lung cancer and 60 patients with head and neck squamous cell carcinomas. While ERCC1 is associated with DNA repair, CCTα is involved in the synthesis of a major component of cell membranes and active in membrane-mediated signaling and embryo survival.