by Nikou Kelardashti

Graphic design by Brendan Lazar

In the intricate world of neurosurgery, Dr. Gelareh Zadeh stands as a beacon of innovation, reshaping patient care and pushing the boundaries of scientific inquiry. As a Professor at the Department of Surgery at University of Toronto, Head of Neurosurgery at Toronto Western Hospital, and Senior Scientist at Princess Margaret Cancer Research Institute, Dr. Zadeh’s impact in the field of neurosurgery and neuro-oncology is vast and transformative. 

The desire to have a direct, tangible impact in the world emerged as the primary motivation guiding Dr. Zadeh toward a career in medicine. However, her interest and motivation to pursue research deepened as she started to pursue the field of neurosurgery. Dr. Zadeh explains “the field has a lot of potential. It is in its infancy and has room to grow in how we treat patients, advances that will directly impact patients and change how we practice.” Driven by these insights, she embarked on a journey that led to her pursuit of a PhD at University of Toronto, where she actively engaged in “learning the new language of research.” 

During her PhD, Dr. Zadeh focused on tumour angiogenesis, a process characterized by the growth of new blood vessels within a tumour. These blood vessels play a crucial role in growth and progression of cancerous tumours. Dr. Zadeh’s focus was to investigate the factors influencing this blood vessel development and understand its implications for diseases, vascular malformations, and other complications. During her PhD work, Dr. Zadeh maintained a broad approach, remaining open to different subspecialties within the field of neurosurgery. 

When Dr. Zadeh established her own laboratory, molecular genomics and epigenomic profiling had gained significant popularity. Reflecting on this era, Dr. Zadeh draws a parallel to current times, stating, “I think what molecular biology was then is what AI [artificial intelligence] is now”. Consequently, her lab focused on establishing markers of brain tumours. It was then that she focused on researching tumours which were relevant to her clinical practice, including meningioma, schwannoma, and glioma. These tumours differ in the types of cells from which they originate. Meningiomas originate from the meninges, which are the tissue layers that cover the brain. Schwannomas originate from Schwann cells, which produce myelin (the protective covering around peripheral nerves). Lastly, gliomas originate from the glial cells, which are the supportive cells of the central nervous system.¹ For tumour research associated with these three cell types, Dr. Zadeh and her lab focused on establishing multiplatform understanding of tumour biology. This approach facilitated improvements in diagnosis, development of predictors for treatment response, and overall advancements in understanding and managing these tumour conditions.

Meningiomas are one of the most prevalent types of brain tumours.² Traditionally, the classification of the specific subtypes of these tumours relied on histopathology according to the World Health Organization. However, this classification has proven inadequate in accurately representing the clinical behavior of all meningiomas.² Dr. Zadeh and her team have combined various molecular genomic techniques and pioneered a new classification system, which demonstrates a more reliable prediction of tumour behavior and recurrence compared to histopathology-based classification. The implementation of this innovative approach holds the potential to enhance therapeutic decision-making significantly.

Despite being a prevalent type of brain tumour, meningiomas have unfortunately received insufficient attention due to a lack of awareness and advocacy for further research. To address this gap, in 2016, Dr. Zadeh co-founded and currently leads the International Consortium on Meningiomas (ICOM). ICOM is a multidisciplinary and multi-institutional collaborative group with the aim of increasing awareness of meningiomas. ICOM brings international institutions together to optimize research by pooling data, samples, and patient information. Dr. Zadeh reflects on the success of the consortium, stating it “allowed us to build that momentum to the point that when we introduced it in 2016 to now it has become the mainstay of the scientific meeting that happens every year at society of neuro-oncology. More than 120 members work together, collaborate, and produce publications.”

Dr. Zadeh and her team have also made significant strides in the development of non-invasive diagnostic tools. Traditionally, accurate diagnosis of intracranial tumours required invasive surgery to obtain tissue samples. However, Dr. Zadeh’s ground-breaking research has demonstrated that plasma obtained from a blood sample contains DNA-methylation profiles that can enable the discrimination of common intracranial tumours.³ This non-invasive approach mitigates the risks associated with invasive surgery for tissue sampling. Consequently, this innovative method, through a simple blood test, facilitates risk assessment for tumour development, enables early detection, and, by classifying the tumour, empowers clinicians to choose the most effective treatment approach.

All these research projects are meticulously designed to efficiently address the needs of both patients and clinicians, ensuring that the findings seamlessly translate into clinical practice. The success of this integration is attributed to Dr. Zadeh’s dual role, actively engaged in both clinical and research fields. As a clinician-scientist, Dr. Zadeh holds a unique position, shaping her research questions based on invaluable insights gained from daily experiences in clinical settings and operating rooms. Dr. Zadeh emphasizes, “it is that day-to-day in clinical and operating room that I see these questions that are presented to us and how do we do better because there are gaps and limitations in what we can do. So having that perspective of a clinician is very helpful.”

Additionally, Dr. Zadeh and her team are at the forefront of innovative clinical trials aimed at enhancing treatment for glioblastoma, an exceptionally malignant form of glioma with a challenging prognosis.⁴ Notably, Dr Zadeh’s team has successfully classified different types of glioblastomas based on their immune microenvironment. Within this classification, a subset of glioblastomas exhibit an immunosuppressive microenvironment, which makes them resistant to traditional immunotherapy. Dr. Zadeh explains, “the emerging technology is for us to change the method by which we have been trying to make advances and that is to change the mechanism by which we deliver treatment into the tumour.” In response, to tackle this subtype of glioblastoma tumours, they inject the tumour with oncolytic viruses to infect cancer cells and stimulate an immune response.⁴ This strategic shift to a more immunogenic microenvironment enhances the effectiveness of immunotherapy. 

In conclusion, Dr. Zadeh’s profound contributions to the field of neurosurgery underscore her unwavering commitment to advancement. As the first female chair of neurosurgery at the University of Toronto, she breaks barriers leaving a significant mark on the scientific and medical landscape. Dr. Zadeh’s legacy extends beyond her ground-breaking research, resonating in the inspiration and guidance she provides to the next generation of medical professionals, setting a powerful example for inclusivity and excellence in the ever-evolving field of neurosurgery.

References:

1. Mayo Clinic. “Brain Tumor – Symptoms and Causes.” Mayo Clinic, 21 Apr. 2023, http://www.mayoclinic.org/diseases-conditions/brain-tumor/symptoms-causes/syc-20350084.

2. Nassiri F, Liu J, Patil V, et al. A clinically applicable integrative molecular classification of meningiomas. Nature. 2021 Sep 2;597(7874):119-25.

3. Nassiri F, Chakravarthy A, Feng S, et al. Detection and discrimination of intracranial tumors using plasma cell-free DNA methylomes. Nature medicine. 2020 Jul;26(7):1044-7.

4. Nassiri F, Patil V, Yefet LS, et al. Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial. Nature Medicine. 2023 May 15:1-9.