For Brain Tumour Awareness week, we spoke with neurosurgeon Dr. Gelareh Zadeh, Medical Director of the Krembil Brain Institute. Here are some questions and answers from the conversation with Dr. Zadeh, who talked about the most recent advances in Glioblastoma research that she hopes will one day positively impact outcomes for patients and increase survival rates.
Q: What makes Glioblastoma so challenging to treat, and ultimately to cure?
A: The biggest challenge is the infiltrative nature of the tumour. We can mostly remove the mass by surgery, however the microscopic invasive cells are what result in the tumour being aggressive, difficult to treat, and why it often recurs within a short period of 18 months.
Beyond this, one of the most difficult elements of treating Glioblastoma is that the disease affects the individual and who they are as a person. It can affect personality, brain function: arm movement, leg movement, speech, memory and as a result, have a negative impact on a patient’s quality of life.
From the time you present with Glioblastoma, survival rates are often less than two years, with recurrence being an inevitability. Our research focuses on new ways to attack the invasive cells that have spread through the brain, like roots from a tree.
Q: What other types of advancements have been made in Glioblastoma research at UHN?
A: We have shown that a particular genetic test – called methylation profiling – can help refine the diagnosis of brain cancers. There are compounds that we can measure which tell the surgeon the diagnosis immediately in the operating-room and allow the surgeon to know what genetic subtype of Glioblastoma we are working on. Currently during surgery, although our pathologist tells us that it’s a Glioblastoma, the genetic makeup of that individual patient’s tumour is not known. Understanding the genetic makeup of the tumour can help surgeons make more accurate decisions in real time, during the surgery.
We are also working on the ability to detect cancer in the blood stream of patients who have a Glioblastoma and we are focusing on ultimately using this research approach to create a diagnostic test that could determine whether you’re developing a brain cancer significantly earlier than what may appear in brain imaging.
Q: What is your current research focus?
A: Investigating new treatment options to start clinical trials more rapidly is where I would like to focus our efforts. One of the biggest barriers is finding drugs that work against Glioblatoma and understanding whether the compounds even make it into the tumour at sufficient dose/concentration/duration levels.
Repurposing existing drugs is promising because we can test compounds in a more rapid cycle than creating drugs from scratch. We’ve recently done a study to look at how the cancer cells in a Glioblastoma process sugar and through that research, have found existing compounds that can target that machinery and decrease the growth of the cancer cells.
We’ve already identified compounds called azoles that are from a class of antimicrobials and we have sufficient research lab data to show they can be of promise. This group of compounds has been shown to halt the tumour’s metabolism and can hopefully restrict Glioblastoma cells’ growth in patients.
We have a first-of-its-kind clinical trial ongoing right now where we are hoping to be able to demonstrate that. One of the unique features of this Phase Zero clinical trial is that the compound is given before surgery so that we can, at the time of re-section of tumour, confirm that the drug has actually made it into the tumour. This has never been possible before and is incredibly important to understand in the context of potential new therapeutic options in future.
Q: What inspires you to do what you do?
A: Why do I do what I do? It’s because I want to help my patients the best I can. As a neurosurgeon, in the majority of my patients with brain tumours, I can remove the tumour and have a positive impact, and often cure the patients.
But there are a number of Glioblastoma cases where my impact as a surgeon is limited. I can resect 80 per cent to 90 per cent of the tumour but that additional component that’s left behind is where the challenge remains. So when I think about why I want to understand more about the tumour biology, it’s really to be able to tackle that 10 per cent to 20 per cent that we can’t help with surgery.
That’s why we do the research that we do. We want to understand more about the biology of the tumour, why the cells came about in the first place, what makes them grow and where can we intervene to stop the tumour cells from growing and from coming back.
That’s where my motivation comes from, to be able to find cures that add to surgery and that can ultimately prolong our patients’ lives and help them have a better quality of life. Interacting with the many brave patients who come through every year and together with their loved ones face this aggressive cancer is where we get our motivation to work towards a cure.
Funding for this research was made possible by the Wilkins Family Chair in Brain Tumor Research and MacFeeters-Hamilton Neuro-oncology Program.