A research team comprised of several US universities and ITMO University in Russia has identified a number of new driver mutations in lung cancer cells that may be responsive to genomically targeted therapies as well as immunotherapy. For the study, researchers examined 1,144 genome profiles of cancers from patients with two common types of lung cancer: lung adenocarcinoma and lung squamous cell carcinoma. According to Science Daily, the high statistical significance of the study enabled the identification of novel driver mutations that affect the activity of several proteins responsible for signaling in cells.
The scientists used statistical methods to distinguish likely driver mutations from the so-called “passenger” mutations that occur during cancer development but do not provoke tumor growth. The researchers detected 38 significantly mutated genes in lung adenocarcinoma and 20 in lung squamous cell carcinoma, although only 6 mutated genes were shared by both types of tumors. This suggests that even though both types arise in the same organ, they notably differ from each other.
The comparison of discovered genome variants with the other 19 cancer types have showed that lung squamous cell carcinoma is more similar to head and neck tumors and to a subset of bladder carcinomas than to lung adenocarcinomas, as indicated in the Science Daily report. In addition, the analysis identified several predicted neoepitopes, which are protein fragments that serve as markers to identify and fight cancer, in most cases of lung cancer. Therefore, 47% of lung adenocarcinoma and 53% of lung squamous cell carcinoma samples have at least 5 predicted neoepitopes, which suggests a promising potential for immunotherapy.
Immunotherapy may have a potential advantage over chemotherapy and radiotherapy because it targets tumor cells and spares the healthy cells. “Cells constantly provide protein pieces called epitopes to the immune system for review. If for some reason, the immune system is not able to capture the epitope of a mutated protein and misses it, the tumor may arise,” explains Anton Aleksandrov, an ITMO University researcher. “The search for epitopes that can be detected by the immune system of a patient is critical to the development of individual treatment strategies for cancer. Attached to proteins, neoepitopes will prompt the immune system where its help is needed.”
“We have identified several distinct recurrent mutations that are likely to be recognized by the immune system and therefore would be strong candidates for cancer vaccines,” says lead author of the paper Joshua Campbell. “Future studies are needed to determine what allows a mutation in a gene to cause uncontrolled growth in one type of cell but not in another type. This knowledge will give us a more complete understanding of the molecular pathways involved in tumor growth and help us design better drugs.”
Source: Science Daily