microRNAs are critical to cancer researchers, particularly in leading them to a breakthrough in cancer diagnosis or treatment. Research has shown that miRNAs, single-stranded molecules that regulate gene expression, may be an important driver in cancer development. Now researchers believe they may also… key to killing cancer cells.
In a major new study published this month in scientific signalingResearchers at Boston University School of Medicine (BUSM) looked at KRAS mutant non-small cell lung cancer (NSCLC) based on its two subtypes, epithelial and mesenchymal. They found that although mesenchymal NSCLCs are less responsive than epithelial NSCLCs to inhibition of the RAS pathway, mesenchymal tumor cells are particularly sensitive to miR-124.
When there was a loss of miR-124 in the mesenchymal tumor cells, there was an increase in cell survival. On the other hand, when there was an overexpression of miR-124, apoptosis or cell death was activated. This finding led the researchers to conclude that miR-124 may be an alternative molecular target for the treatment of the mesenchymal subtype of NSCLC.
“By understanding the mechanisms associated with phenotypic heterogeneity in lung cancer cells — particularly differences between epithelial and mesenchymal cells — these differences can be exploited to develop more selective therapeutic agents,” said corresponding author Anurag Singh, PhD, assistant professor of pharmacology and medicine at BUSM, in a press release announcing the findings.
Mesothelioma is a cancer associated with asbestos exposure that affects the lining of the lungs or abdomen. It is an aggressive cancer that is often resistant to chemotherapy and radiation. However, patients with mesothelioma and patients with lung cancer often undergo the same treatments, making this finding important for mesothelioma care. Nearly 3,000 new cases of mesothelioma are diagnosed each year in the United States.
The researchers used what they call mesenchymal-like cells that had undergone a switch known as epithelial to mesenchymal transformation. Other studies have shown that the transition from epithelium to mesenchymal in mesothelioma cells, suggests the potential for using microRNAs in innovative treatment therapies to suppress tumor growth in lung cancer and malignant mesothelioma patients.
The mesenchymal-like cells are resilient and fight chemotherapy agents that should lead to their death. However, when the researchers looked more closely at the role miR-124 had on the cancer cells, it was an indicator of whether the cancer cells would respond to chemotherapy, according to Medical News Today.
Targeted therapy for mesothelioma and lung cancer patients optimizes the potential for treatment success and provides treatment options that may not have otherwise been considered. Each new breakthrough in cancer research brings hope to mesothelioma patients. Although the rare cancer is terminal, each major finding brings a cure one step closer.
The BUSM researchers hope their discovery leads to clinical trials for NSCLC patients, but they point out that “additional work needs to be done to investigate this potential therapeutic target.”
Read the full study in the September issue of Science Signaling.
- scientific signaling
- (University School of Medicine) BUSM
- Medical news today