Lung cancer kills more people than any other form of cancer — partly because it is often diagnosed at such an advanced stage that few treatment options are possible. A team led by A*STAR has now discovered a pair of small, noncoding RNA molecules that could enable earlier detection and potentially new therapies1.
These two microRNAs “can behave as an early warning signal that the disease has disseminated beyond the primary tumor to a distant site,” says Wai Leong Tam, a researcher at the A*STAR Genome Institute of Singapore who led the study. “This can prompt oncologists to perform more thorough examinations or implement new treatment regimens for patients.”
Lung tumors contain a variety of different cell types, including a rare subset known as tumor-initiating cells (TICs), or cancer stem cells considered to be key drivers of disease relapse and spread throughout the body. Tam and his A*STAR colleagues teamed up with physicians from two nearby cancer centers in Singapore to identify regulatory microRNAs that are essential for TIC function.
The researchers obtained biopsies from patients diagnosed with non-small cell lung cancer, isolated TICs from the tumors, and then compared the expression pattern of microRNAs in these cells with those from non-TIC tissue taken from the same patient samples.
Tam’s team found a slew of microRNAs that were either expressed at much higher or lower levels in the TICs. However, they focused in depth on just two, miR-1246 and miR-1290. These microRNAs were the most up-regulated and had never been characterized before. Observations and experiments showed that both play a critical role in helping seed new tumors at distant sites outside the lungs.
The researchers tracked the levels of miR-1246 and miR-1290 in patients undergoing therapy. “As expected, the higher expression levels of those two microRNAs in malignant tissues consistently predicted poorer survival outcomes in a large cohort of lung cancer patients,” says Wencai Zhang, who worked on the study as a research scientist at A*STAR, prior to moving to his current position as a research fellow at Harvard Medical School in the United States.
The microRNAs could serve as a useful predictive biomarker of expected patient outcomes. They might also provide promising drug targets. The researchers wiped out the microRNAs with a special kind of drug known as a locked nucleic acid in mouse models and saw reduced tumor growth. The same kinds of drugs are now being used in humans for other diseases, and could prove helpful in treating lung cancer.