Scientists have discovered a mechanism in non-small cell lung cancer (NSCLC) cells that contributes to their ability to maintain and grow tumors.
The previously unknown mechanism was brought forth by researchers at Virginia Commonwealth University Massey Cancer Center led by Charles E. Chalfant, associate professor of biochemistry and molecular Biology.
The researchers believe that narrowing in on this mechanism could provide a breakthrough for the development of effective therapies for NSCLC and other cancers.
The findings provide the first example of a protein factor regulating the expression of the protein caspase-9, a main player in apoptosis, or programmed cell death.
Scientists have known that healthy cells favor caspase-9a, a form of the caspase-9 protein that promotes natural apoptosis but Chalfant and his research team found that NSCLC cells favor caspase-9b, which is the anti-apoptotic form of caspase-9 that promotes tumor formation, growth and maintenance.
Their further investigation discovered that a protein known as hnRNP L functions as an RNA splicing factor by promoting the expression of caspase-9b through a process known as RNA splicing.
"We're researching an unexplored area of RNA splicing factors in relation to cancer. Before this study, there had been very little evidence of an RNA splicing event that results in cancerous tumor development.
This study points to caspase-9b as being a very important target in the development of a durable therapy for non-small cell lung cancer," said Chalfant.
The researchers used mouse models for the study.
"Unfortunately, many current therapies for lung cancer are less effective and more toxic than we'd like.
Lung cancer kills more people than any other cancer, and there is a real need for new cellular targets that are cancer-specific and show results in large numbers of patients regardless of the mutations found in individual tumors," noted Chalfant.
Since caspase-9b is mainly expressed in malignant cells, these findings may provide innovative treatments for non-small cell lung cancer with little to no toxic side effects," he added.
The full report of the study is published in Journal of Clinical Investigation.