patients remains unsatisfactory. So there is still a lot of work that needs to be done. IBTA: What are your current areas of research? EW: My team at Beth Israel Deaconess Medical Center is working on the clinical and basic science translational research on alternating electric fields therapy, as well as cerebrospinal fluid biomarkers and advanced MRI research. All of our effort is aimed at translating our cutting edge understanding of the physiology and biology of brain tumors into clinical practice and treatment. Knowledge about the mechanisms of action and the science behind alternating electric fields therapy is still emerging. At first glance, it is hard to understand how these fields can get from the surface of the scalp into the brain tumor. But the way that energy from the electromagnetic spectrum penetrates any surface really depends on its frequency. This was actually my first question when I originally heard about this therapy and I found a paper showing that the permittivity (a measure of the ease at which electromagnetic waves penetrate a medium) for skull, gray matter and white matter were similar at the frequency of 200 kHz. Then the next question is how it works and for that I needed help from colleagues smarter than me from the field of Signal Transduction. After about three or four years of cell biology research, my long-time collaborator Ken Swanson, Ph.D. and I are quite confident that the alternating electric fields disrupt the orderly execution of tumor cell division during mitosis. This results in the abnormal segregation of chromosomes that contain the necessary DNA materials to each daughter cell, as well as marking the cells for immune destruction. It is reassuring to know that the recently announced interim trial result showed a survival advantage when alternating electric fields therapy was added to standard treatments in newly diagnosed glioblastoma patients.
unknown is always out there. Someday, someone may stumble on one of these unknown unknowns and transform brain tumor treatment in a quantal fashion. Right now the sequencing data coming out, either from exome or whole genome sequencing, indicate that there is heterogeneity in brain tumors, particularly for the malignant gliomas. This mutational heterogeneity not only differs among patients, but also within the same tumor from each individual patient. In fact, single-cell analysis has shown that the type of somatic mutations can differ from cell to cell. By the time the malignant glioma is detected it has already evolved quite a long way in the process of accumulation of genetic and epigenetic changes over time in individual cells. This becomes “a true mess” from a therapeutic standpoint. I really think that we need to turn back the clock and work on earlier diagnosis and intervention. This is similar to Alzheimer’s or other types of neurodegenerative diseases associated with the pathological aggregation of tau protein in the human brain and where researchers are now working on earlier detection and therapies rather than later interventions when treatments do not have a chance to work. But they have more time on their hands because the diseases take years or perhaps a decade to evolve.
IBTA: What are your thoughts on the future of brain tumor treatment? EW: I would like to emphasize that research is unpredictable and quite often winds up in a dead-end. I think time will improve our cumulative understanding of the biology of brain tumors and their implications for treatment. Therefore, I can only speak about what I know right now. But the unknown
IBTA: What is the most challenging part of your work? EW: The most challenging part is dealing with the patients’ psychosocial issues while treating their disease. A patient has to deal with the challenge of his or her brain not functioning well. That dysfunction may interfere with work, driving and relations with family members.
Above: Eric and his daughter Erika leading a group
Above: The Wong family with A Reason To Ride
of riders at the A Reason to Ride Bikeathon in 2014
organizer Tom and Judy DesFosses and friends and supporters. Eric’s wife Ling speed-knit this blanket in a “Knitathon” and then donated it for auction.
The driving and work issues are particularly challenging because if patients cannot drive they cannot get to work and then they may lose their health insurance. Depending on the location in the brain that is affected, the patient may have various neurological syndromes such as a language problem (aphasia), distortion of the senses or motor dysfunction, all of which affect their activities of daily living and make them dependent on others. Furthermore, the brain and the rest of the central nervous system can be impaired by our treatments, like surgery, radiation and/or chemotherapy. Therefore, the brain tumor not only affects the patient, it also affects the patient’s family and caregivers. IBTA: What is the most gratifying part of your work? EW: The most gratifying part is when a patient or his/her family member expresses their gratitude to me. I remember one incident more than 10 years ago when I was waiting for a bus at Logan Airport in Boston. The son of a former patient who had died a few months before thanked me for caring for his father while I was waiting for the bus. That beats any professional accolade that I ever received. Now, every September, I have a special opportunity to meet my patients and their family members in the A Reason To Ride bike-a-thon organized by Tom DesFosses, who is currently in remission for his primary CNS lymphoma. It is a yearly event that my family would not miss, especially my daughter, Erika, who started leading the ride in her tricycle when she was three. Now, she is ten and we look forward to leading the ride every September. n Brain Tumour
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