Professor Kwang-Hyun Cho and his team from the Department of Bio and Brain Engineering have successfully identified the potential target genes that can help overcome the resistance of colorectal cancer cells to the antibody known as cetuximab.
Colorectal cancer is the abnormal growth of invasive cells that develop in parts of the large intestine, specifically the colon or the rectum. The number of colorectal cancer cases has abruptly increased recently to one million worldwide. In Korea, the adoption of westernized eating habits and overconsumption has caused an increase in diagnoses of the disease.
Cetuximab is currently used as an antibody for colorectal cancer treatment. It specifically targets cells related to epidermal growth in order to control the unwanted proliferation of cancer cells in the large intestine. However, the antibody’s effectiveness is very limited in that it is only applicable to patients with wild-type KRAS (WT KRAS), a non-mutated gene that controls cell growth, cell maturation, and cell death. In fact, it has been reported that cetuximab has not been as responsive as expected.
To overcome such resistance to the antibody, Professor Cho and his research team analyzed gene expression data from colorectal cancer patients. They discovered that a knockdown in one of the five different target genes that have been identified (DUSP4, ETV5, GNB5, NT5E, and PHLDA1) can help increase sensitivity to cetuximab for patients with WT KRAS cells. Most importantly, the team also discovered that the applicability of cetuximab can be further broadened by constraining the GNB5 gene, as it can increase the patient’s sensitivity to cetuximab even for KRAS mutant cells.
Professor Cho stated that the discovery of the new target genes provides a “promising target for combination therapy with cetuximab irrespective of KRAS mutation.”