Driver Mutations in Common Lung Cancers May Allow for Targeted Therapies

Driver mutations in lung adenocarcinoma and lung squamous cell carcinoma differ from one another, contradictory to previous theories.

In a recent study, driver mutations in lung cancer cells were discovered, and researchers believe these mutated cells could be responsive to targeted therapies and immunotherapy.

Researchers analyzed the genome profiles of 1144 patients with lung adenocarcinoma and lung squamous cell carcinoma. Statistical methods were used to distinguish the driver mutation from the passenger mutations that happen during cancer development, but do not enable tumor growth, according to a study published by Nature Genetics.

Researchers identified 38 mutated genes in lung adenocarcinoma and 20 in lung squamous cell carcinoma, but only 6 mutated genes were shared by both. Although these are both lung cancers, they clearly differ significantly.

Researchers found that genome variants in lung squamous cell carcinoma is more similar to head and neck cancers than to lung adenocarcinoma. According to the study, several predicted neoepitopes, which are protein fragments that can be recognized by the immune system and serve as markers to identify and fight cancer, were identified in most cases of lung cancer.

There were at least 5 predicted neoepitopes seen in 47% of adenocarcinoma samples and in 53% of lung squamous cell carcinoma samples. Researchers said this suggests a potential for immunotherapy.

"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," said lead author of the paper Joshua Campbell, PhD.

Immunotherapy can provide advantages over chemotherapy and radiotherapy as well, since it targets tumor cells specifically and leaves healthy cells unharmed, according to the study.

"The immune system is highly selective; we simply need to suggest our organism that it didn't notice something really important," said researcher Anton Aleksandrov, who was involved in software development for the immunological study. "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. 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."

Researchers previously believed that major driver mutations would be the same in both types of cancer, but the new findings indicate the underlying cell type is a deciding factor in whether or not the mutation causes cell to multiply, according to the study.

"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," Dr Campbell concluded.