Lung cancer tumor growth halved with new approach

New research from Sweden has taken strides toward finding a cure for lung cancer. It focused on noncoding molecules that have been puzzling scientists for a long time.

According to the National Cancer Institute (NCI), lung cancer caused around 25.9 percent of all cancer-related deaths last year and accounted for 13.2 percent of all new cancer diagnoses in the United States.

But the prognosis for this and other cancer types may be looking up; researchers from Sahlgrenska Academy at the University of Gothenburg in Sweden have conducted a meticulous project investigating the role of long noncoding RNA in the development of cancer tumors.

RNA acts as a messenger for DNA information, carrying out its instructions and regulating protein biosynthesis. But there is another type of RNA known as "noncoding RNA" that is not involved in the protein synthesis process.

Noncoding RNA has long remained mysterious, but little by little researchers have been uncovering the fact that it is not devoid of function. Noncoding RNA, as it turns out, seems to be involved in the regulation of cell division cycles.

This function also implicates noncoding RNA in the development and growth of cancer tumors, allowing certain cells to multiply abnormally.

In the new study, Chandrasekhar Kanduri — a professor of medical biochemistry and cell biology — and colleagues saw that by downregulating noncoding RNA activity, they were able to reduce tumor growth in a mouse model of lung cancer by 40 to 50 percent.

According to Kanduri, "This link [between noncoding RNA and cancer] is known, but no one has made such a broad and extensive analysis previously, nor examined long noncoding RNAs so specifically."

The team's findings were recently published in the journal Nature Communications.

'A future for RNA-based treatment'

In their project, Kanduri and colleagues looked at 16 types of cancer, analyzing 6,419 solid tumors and 701 samples of healthy tissue (which they used as control material).

The researchers' initial aim was to identify the molecules of long noncoding RNA active during the so-called DNA synthesis phase of cell division, in which genetic information is replicated.

"Since there is a strong link between cell division cycle and cancer," says Kanduri, "we are using it as the basis for identifying the important long noncoding RNA molecules that play a key role in cancer growth."

"Higher expression of some of these long noncoding RNA molecules during [the] cell division cycle may cause cells to divide uncontrollably to become cancerous," he adds.

To identify the relevant molecules, they used RNA sequencing — a tool that allows researchers to view the range of expressed RNA — and technology specially developed in the Sahlgrenska Academy laboratory.

They were able to pinpoint 570 noncoding RNA molecules expressed differently in different types of cancer. They also found 633 new biomarkers "with high prediction accuracy" for 14 types of cancer.

To better understand how these discoveries may help specialists to treat cancer, Kanduri and team worked with mice grafted with human lung cancer tissue.

Twice every week, they injected the mice with locked nucleic acid antisense oligonucleotides, an agent that blocks the action of relevant noncoding RNA.

Within 15 days of this therapy, the researchers saw that the cancerous tumors had almost halved in size.

"Thus we have identified a new method, optimized it in a lab environment, and identified long noncoding RNA molecules that are involved in uncontrolled cell division. By taking aim at these specific molecules, we have reduced cancer growth. Furthermore, the molecules can also be used to predict the disease."

Chandrasekhar Kanduri

Following this initial success, Kanduri and colleagues suggest that this method might, in the future, be used to treat lung cancer in humans, with equally favorable outcomes.

"We are proposing that this RNA-based method be used to treat lung cancer, for which the survival rate after 5 years is currently only 18 percent," he notes.

"We need to conduct more studies to see if there is potential to carry out clinical trials in patients, but we believe there is a future for RNA-based treatment in the treatment of cancer."