Turning Off the Cancer Switch
By Charmaine Gaudet, APR, BHCRI Communications Advisor
Imagine being able to turn cancer off with a switch.
If this sounds far-fetched, consider that within our genome, which is the entire set of DNA instructions found in a cell, there are genes that act to suppress or ‘silence’ tumours by either slowing down their cell division or causing them to die. While these good genes remain turned on, they hold tumour cells at bay. But sometimes they get turned off – often by a gene mutation – and when this happens, tumour cells can grow out of control, leading to cancer.
Dr. Tom Belbin – Photo provided
Genetic scientists are zeroing in ever closer on the genes and genetic changes that enable cancer to form, grow and spread. One of these scientists is Dr. Thomas Belbin, GlaxoSmithKline (GSK) Chair in Oncology Research at Memorial University and an Associate member of the Beatrice Hunter Cancer Research Institute.
Dr. Belbin specializes in the genomes of head and neck cancer cells, which occur in tumours found in various parts of the nose, mouth or throat. Last year, 7,500 Canadians were diagnosed with some form of this cancer.
“My research focuses mainly on finding novel genes that cancer cells like to “silence”. They do that not by mutating or deleting the gene but by suppressing expression of the gene using the cancer cell’s own regulatory machinery. So, part of my work involves identifying novel genes that fall into this category, and trying to figure out what they do,” says Dr. Belbin.
His lab has looked at several genes that code for KRAB-ZNF proteins, a known cancer suppressor protein. “Head and neck tumours, as well as other solid tumours, silence these genes with a high frequency, although we don’t really know what they do. So, there are several projects ongoing in my lab to turn these genes back on, and then observe how their re-expression this affects a tumour cell’s behavior.”
Dr. Belbin goes on to explain that “silenced genes are not “broken” (i.e., mutated or deleted). They are usually intact but have been switched off. Discovering ways to switch those genes back on could provide a very promising approach to cancer therapeutics in the future.”
In addition to studying how tumours behave towards cancer-suppressing genes, Dr. Belbin and his team are also gathering insight into what makes these tumours tick. Tumours, it turns out, have unique molecular profiles like individual fingerprints. “These ‘molecular profiles’ of tumours give us a window into subtypes of the disease that we never knew existed. When combined with sophisticated machine learning with computers, you can utilize this information to try to make predictions about things such as a patient’s outcome, their response to radiation treatment, or a particular chemotherapy.”
This approach to treating tumours based on the unique molecular or genetic profile of the patient or tumour is referred to as ‘personalized medicine’. It can take much of the guesswork out of treatment. “Instead of trying different treatments until we find one that works, we can instead zero in on the most effective treatment straight away, thereby saving time and cost, as well as offering an effective approach to treating the patient.”
Dr. Belbin is passionate about finding better ways to treat head and neck cancer, a devastating disease that can impact essential functions like the ability to swallow and talk. Surgeries to treat the disease can have psychological effects related to body image or loss of function. “The more we understand about the disease, the more we can give only the necessary treatment; de-escalating treatment often spares the patient unnecessary surgery or other therapies and is more cost effective.”
He says there are many reasons to be hopeful. Medical research into head and neck cancer is advancing rapidly. Survival rates for this disease are improving, albeit slowly, and new drugs are coming on the market all the time. “There is exciting work being done in the field of immunotherapy with inhibitors to PD-1 and PD-L1 that can help the body recognize and attack cancer cells. We also know a lot more about the role of HPV in head and neck cancer, and there is ongoing research to examine whether HPV vaccines that are currently used might be effective at preventing some of these cancers.”
He believes that one of the next biggest breakthroughs will be at the genetic level. “The ability to sequence entire genomes in one experiment or measure the expressions of all genes simultaneously is a window into cancers that we never had before.” He credits the Terry Fox Marathon of Hope Cancer Centres Network’s bank of genomic data as a critical piece of the puzzle. “When researchers and clinicians across the country come together to build this large repository of data about thousands of patients, and then share that data with researchers, it will be a virtual goldmine of new information for researchers.”
He says that new technologies to help detect cancer at the cellular level represent another promising area. “Cells undergo a variety of molecular changes very early in their transformation to a cancerous cell. So, while cells may look relatively normal in a microscope, many of the changes at the molecular level are already taking place. Our ability to detect those changes is crucial to catching the disease at a much earlier stage, when it can be much more treatable.”
Strides in medical research, including the work led by Dr. Thomas Belbin, are giving rise to significant discoveries and new treatments for patients with head and neck cancers. Futuristic-sounding technologies like immunotherapy and genomic medicine are becoming mainstream clinical tools that are transforming the way we diagnose and treat all kinds of cancers.
So maybe the notion that we could one day turn cancer off with a switch doesn’t seem so far-fetched at all. And with the ability to switch cancer-suppressing genes back on once they were turned off, we’d finally be able to beat cancer cells at their own game.