Bern researchers discover new cancer treatments in the “dark matter” of the human genome

Researchers of the University of Bern and the Inselspital have developed a screening method to discover new drug targets for cancer treatments in the so-called “dark matter” of the genome.

In Switzerland, cancer is the second leading cause of death. Among the different types of cancers, non-small cell lung cancer (NSCLC) kills the most patients and remains largely incurable. Unfortunately, even newly approved therapies can extend the life of patients only by a few months and only few survive the metastatic stadium long-term, making new cancer treatments which attack the disease in novel ways highly sought after.

In a recently published study in the Journal Cell Genomics, researchers of the University of Bern and the Inselspital determined new targets for drug development for this cancer type.

For new targets, they looked at the poorly-understood class of genes called “long noncoding RNAs (RiboNucleic Acids)” (lncRNAs). LncRNAs exist in abundance in the so-called “Dark Matter”, or non-protein-coding DNA, that constitutes the vast majority of our genome.

As the name long noncoding RNAs implies, unlike messenger RNAs (mRNAs), they do not encode the construction plans for proteins. Like for mRNAs, the building instructions for lncRNAs are contained in the cell’s DNA.

To study the role of lncRNAs in NSCLC, the researchers started by analyzing publicly available datasets to see which lncRNAs are present in NSCLC.

Therapy development and application to other tumor types

The Bern researchers applied their screening system to two NSCLC cell lines derived from patients, and looked how the inhibition of the selected lncRNAs affected so called “hallmarks” of cancer cells. Hallmarks are cellular behaviors that contribute to disease progression: Proliferation, metastasis formation and therapy resistance.

“The advantage of assessing three different cancer hallmarks is that we have a comprehensive view but also have substantial amounts of data from different experiments, from which we needed to derive a single list of long noncoding RNAS that are important for non-small cell lung cancer,” says Rory Johnson, Assistant Professor at the University of Bern, who led the NCCR RNA & Disease funded project.

The researchers are continuing their research in pre-clinical cancer models and are considering collaborating with existing companies or creating a start-up in order to develop a drug to treat patients.