A researcher at Children’s Medical Research Institute (CMRI) has shown that a new molecule, NU-1, can stop cancer cells growing indefinitely. Dr Scott Cohen, a Senior Cancer Researcher at CMRI, says the research is a great example of how international collaboration and the right expertise can quickly advance scientific research.
“In 2018, I received an exciting email from Professor Karl Scheidt, a chemist at Northwestern University in the US,” Dr Cohen said. “They had created a new molecule that showed promise in stopping cancer cells growing. Within a couple of weeks, I was testing NU-1 and establishing how it worked in cancer cells.”
Dr Cohen is an expert on the enzyme telomerase, the enzyme that lengthens the protective caps at the ends of chromosomes called telomeres. Telomeres usually get progressively shorter as cells in the body divide, placing natural limits on cell growth. Cancer cells are different: they can grow indefinitely because they activate the enzyme telomerase, an enzyme that replenishes the protective telomeres each time a cancer cell divides. By continuing to protect chromosome ends, telomerase makes cancer cells immortal. About 90% of all human cancers have activated telomerase.
“There are only a few specialised cells in the body that are immortal in this way, such as stem cells, but the action of telomerase in these cells is controlled. Cancer cells have many mutations that turns these controls off. In cancer cells, the excessive action of telomerase contributes to their aggressive nature.
Stopping cancer cells from maintaining their telomeres is one major avenue of cancer research worldwide and a research focus at CMRI.
Knowing the importance of inhibiting telomerase in cancer cells, a decade of research in Professor Scheidt’s lab went into creating NU-1, which was inspired by a telomerase-inhibiting molecule found naturally in a particular bacteria.
“Naturally occurring molecules are often very large and complex. A chemist examines a natural product and looks for where the action is happening in the molecule – where the important functional part is. The chemist then reconstructs this in the lab in a more efficient manner. This approach led to the creation of NU-1.”
Dr Cohen tested NU-1 on telomerase, and NU-1 appeared to be a very promising inhibitor. But the results were surprising for another reason: NU-1 inhibited telomerase in a way unlike any other molecule. Most inhibitors cause a temporary, and possibly reversible, change in telomerase, but NU-1 forms an irreversible covalent bond with telomerase (like hydrogen and oxygen atoms in water). This permanent effect of NU-1 has promising implications for stopping cancer cells.
“This discovery-based research is an important and essential first step. We need to discover potential tools like NU-1 and establish their effectiveness in the laboratory; after that we can then start thinking about applying these tools to treating cancers. NU-1 is proof-of-principle, and Karl and I are committed to improving and developing NU-1 into an even more specific and effective compound. I was very excited and humbled when Karl asked me to be part of the team.”
It seems very likely that NU-1 or a similar molecule will be the subject of more research as scientists look for the best tools to treat cancer. As well as having expert researchers, CMRI has many world-class facilities and biological tools that are well placed to help this research progress.
“Where you need a lot of testing is in normal, non-cancerous cells. As a cancer researcher your aim is to develop a cancer treatment that has no effect on normal cells. CMRI has many different examples of normal and cancer cells that can be handled in the laboratory in a controlled manner, so we are in a good position to test telomerase inhibitors in a variety of biological settings.”
Based on these exciting findings, the research collaboration between Scheidt and Cohen will continue. They are seeking more funding to develop even better molecules to specifically target telomerase and cancer cells.