Single molecule determines lung cancer cell death

Researchers have identified a molecule that determines whether or not a type of lung cancer cell will undergo cancer cell death. This discovery may lead to better approaches to lung cancer treatment, specialists say.

According to data from the Centers for Disease Control and Prevention (CDC), lung cancer is the leading cause of cancer-related death in the United States. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 85 percent of lung cancer diagnoses in the U.S.

The National Cancer Institute (NCI) note that at present, existing treatments are unable to cure NSCLC in people who have received this diagnosis.

However, we may now be one step closer to finding more effective pathways toward treating NSCLC; a new study led by Dr. Anurag Singh - from the Boston University School of Medicine in Massachusetts - has found that one molecule indicates whether or not some of the more resilient cancer cells die following chemotherapy.

The researchers' findings were published in this month's issue of the journal Science Signaling.

mIR-124 is key to cancer cell signaling

In NSCLC, some epithelial cells - which form part of the lung tissue lining and normally align neatly with each other - transform into mesenchymal-like cells. Mesenchymal cells are non-aligning cells, which are able to "migrate." In the context of NSCLC, they have the potential to become cancerous cells, invading healthy tissue and forming tumors.

The mesenchymal-like cells that result from this "switch" exhibit mutations in the KRAS gene, which plays an important role in controlling cell division. KRAS is a proto-oncogene, meaning that it is susceptible to mutations that allow it to promote the development of cancer.

Cancerous mesenchymal-like cells are very often resilient and typically resist programmed cell death after exposure to chemotherapy.

The researchers found that a molecule called mIR-124, which is involved in the regulation of gene expression, determines programmed cell death in cells that have gone through the epithelial-to-mesenchymal transformation.

Dr. Singh and team were able to identify the role of miR-124 by studying cell models from NSCLC tumors in the laboratory.

First, they confirmed the profiles of different types of lung cancer cells. Then, when they compared the biochemical profiles of the cancerous cells, they were able to establish that miR-124 was key to determining whether or not the type of cell aforementioned would respond to chemotherapy agents.

'Understanding the mechanisms' is crucial

Dr. Singh says that all types of lung cancer have very different characteristics, as well as complex structures. That being the case, he notes, it is of utmost importance that scientists fully understand how these diseases function in order to be able to devise truly effective treatments.

He explains, "Lung cancers display widespread genetic, molecular, and phenotypic variability and heterogeneity. It is critical to understand the implications of this heterogeneity to identify effective targeted therapeutic regimens and clinical diagnostics."

He adds that better understanding the differences between how various cancer cells function will be a key element in this process.

"Understanding the mechanisms that are associated with phenotypic heterogeneity in lung cancer cells - specifically differences between epithelial and mesenchymal-like cells - allows these differences to be exploited to develop more selective therapeutic agents."

Dr. Anurag Singh

The researchers are hopeful that their current findings may lead to preclinical trials of improved NSCLC treatments, though they warn that many additional studies are yet to be done.