Making Oncology His Path: An Interview With Ezra E.W. Cohen, MD

Ezra E.W. Cohen, MD

He traded a rewarding family practice for a career researching head and neck cancers.

Ezra E. W. Cohen, MD, had achieved his childhood dream. He was a doctor in a small Canadian town, treating families for nearly any health issue that cropped up—the flu, injuries, childbirth. On hand for milestones both happy and sorrowful, the physician was forging a special relationship with his patients, and he cherished it.

So his wife was surprised one night when Cohen told her he wanted to leave family practice and become an oncologist.

“I was a small-town doctor for almost two years, and I realized that it didn’t stimulate me in the way that I needed,” said Cohen, 45. “I was also doing some palliative care at the time and was involved with a lot of oncology patients. Clearly, we were not winning the battle, and what I began asking myself was not how to take care of these patients, but why— why does this person get that type of cancer, why does this cancer behave the way it does, and what can we do about that?”

To alter the course of his career, Cohen knew he’d have to pursue another internship and residency. It would mean a lifestyle change for a family that had gotten comfortable in Orillia, Ontario, where their home overlooked a lake.

But Cohen’s wife never flinched. “She was, from day one, completely supportive,” Cohen recalled. “She said, ‘If you feel strongly about this, then this is what you’ve got to do.’”

That support helped shepherd Cohen through a journey that brought him to the United States and transformed the doctor into a leading expert on head, neck, lung, esophageal, thyroid, and salivary gland cancers, and in the development of novel, molecularly targeted therapies for those diseases. His laboratory and clinical research interests also include radiation therapy for non-small cell lung cancer and squamous cell carcinoma of the head and neck, especially ways to combine radiotherapy with novel agents.

As a physician and translational researcher at the University of Chicago Medical Center, Cohen has focused on epidermal growth factor receptor (EGFR) inhibitors, such as gefitinib (Iressa). Cohen and his laboratory colleagues discovered that gefitinib was most effective in patients who developed a rash after treatment, indicating a genetic and pharmacokinetic interaction.

“You had to achieve a certain level of exposure for this drug to be effective, and also there are people who are genetically susceptible to this rash and whose tumors are susceptible to respond to this agent,” Cohen said. “The relationship between the development of the rash and the benefit of these drugs is true not just of this drug, but of every EGFR inhibitor out there in every cancer in which these have been tried.”

Out of that understanding branched several areas of research for Cohen: the mechanism of resistance to EGFR inhibitors, newly identified signaling pathways and the study of agents that might shut them down, toxicity and the genetics related to that toxicity, and why some individuals get the rash and some do not.

Having been the lead investigator of phase I studies of sorafenib and axitinib, Cohen is seeking an answer for patients with thyroid cancer, as well. The discovery that these patients respond very well to drugs that inhibit vascular endothelial growth factor receptor 2 (VEGFR2) has been upheld in phase III studies and, Cohen hopes, will soon be an FDA-approved use for such treatments.

Risk Factors Pose Challenges

At the University of Chicago Medical Center, Cohen serves as associate professor in the Section of Hematology/Oncology, co-director of the Head and Neck Cancer Program, and director of the Hematology/ Oncology Fellowship Program. He spends about 30% of his time seeing patients and managing their care, another 30% designing and running clinical trials and doing administrative work, and the remainder conducting research in his lab.

Since beginning his work with head and neck cancers in 1996, Cohen has found himself responding to a growing change in the demographics of his patients, whose risk factors differ from those prevalent in many other forms of cancer.

The patients these days often are in their 40s and 50s, a decade younger than those he previously treated and, as nonsmokers and nondrinkers, they lack 2 typical risk factors for cancer. Perhaps most importantly, these patients have contracted the sexually transmitted human papillomavirus (HPV), which can cause oral pharynx cancer.

An increase in oral sexual behaviors, coupled with a decrease in smoking, is contributing to a soon-anticipated dominance of HPV-positive oral cancers, likely just the beginning of an epidemic, Cohen said. In general, patients with HPV-positive oral pharynx cancer have a far better prognosis than patients with the disease who do not have HPV— and that has created an interesting scientific challenge for Cohen.

“It’s made us change the way we approach the disease,” he said. “In clinical trials, we’re treating those who are HPV-positive less aggressively, with the thought that, eventually, routine management will be different for HPV-positive and HPV-negative groups.”

Cohen is also part of an effort to decipher the biology of HPV-positive oral pharynx cancer, as a means of learning why some HPV-positive patients don’t fare as well as other patients of the same type when treated. “There’s a large effort in trying to sequence the genome of HPV-positive patients ongoing at the University of Chicago,” he said. “There may be treatments that are specific to HPV-positive versus HPV-negative cancer, targets we may be able to go after in these cancers, and we’re beginning to look at that in different labs at the institution.”

Dr. Ezra Eddy Wyssam Cohen, MD, At a Glance

• Is married and the father of 2 boys, ages 12 and 15. Cohen doesn’t know yet whether his sons have inherited his interest in science. “They like video games,” he said.
• When not working, enjoys bicycling and traveling, and is also learning Italian. “It’s just a beautiful language,” Cohen said.
• A fiction enthusiast, particularly enjoyed A Fine Balance, by Toronto-based author Rohinton Mistry, the story of “a group of people who met by coincidence in India in the ’70s, the politics of the time, and how it impacted their lives.”
• Recalls a job painting parking lot lines, when he was 16 or 17, as his worst ever. “It was boring, it was hot or we had to work in the middle of the night, my boss was a jerk, and it paid terribly,” Cohen said. “I stuck with it for most of that summer, mainly because my friend had gotten me the job.”
• After working as a physician in 2 countries, believes that Canada is better at administering routine healthcare, while the United States is more effective at treating specific illnesses—assuming patients can afford care. Patients in the United States also have higher expectations of their doctors, considering them service providers, Cohen said.
• Lends help to 2 patient advocacy groups, Support for People with Oral Head and Neck Cancer (SPOHNC) and the Head and Neck Cancer Alliance.
• Has won 5 awards from the American Society of Clinical Oncology to support his research, including the Young Investigator Award in 2003.
• Has published 53 peer-reviewed articles, 13 peer-reviewed commentaries, 10 book chapters, and 22 unpublished abstracts.
• Believes that the last few years have been among the worst ever in terms of the availability of funding for cancer research. “When funding begins to dry up like this,” he said, “the projects that are the most interesting and have the most potential to make an impact, but by their very nature tend to be higher risk or a little bit less grounded, are the first ones to go. Hopefully, as we begin to spend less money on fighting wars, some money will turn back to research.”

How a Patient Made an Impact

While Cohen found such scientific challenges of oncology intriguing, he also changed his career trajectory partly because of a patient he met as a family practitioner. The patient was his age, she had small children, and she was dying of cervical cancer.

“I was still a pretty young physician, and here was a patient I could really relate to in age and life experiences,” Cohen said. “The impact of this disease on her and her family really hit home. She was going to leave behind small children, a husband, friends and other family members, and it left me with the feeling that ‘We have to do something about this.’”

For Cohen, doing something about it meant not only pursuing a new avenue of study, but saying goodbye to Canada.

Born in Iraq, where his ancestors went back 10 generations, Cohen and his family had moved to Toronto in the 1970s due to political unrest. He was the son of 2 general practitioners, and remembers that “there was always medicine talk around the house. It influenced us—my brother is a pulmonary doctor in New York.”

Cohen followed that interest to the University of Western Ontario, where he majored in psychology. He earned his medical degree in 1990 from the University of Toronto Medical School, then completed a residency in family medicine at Toronto General Hospital, followed by extra training in obstetrics so that he’d be able to perform cesarean and forceps deliveries.

Yet Cohen could not pursue oncology because of a Canadian law, which has since changed, prohibiting doctors from entering into second residency programs.

“All the doors in Canada were closed,” Cohen recalled. “We never thought we’d ever move to the United States, but I had no choice. I applied to US residency programs and ended up at Long Island Jewish Medical Center,” Albert Einstein College of Medicine, in New York, studying internal medicine.

In 1999, Cohen landed at his current professional home, the University of Chicago, for a fellowship in hematology/oncology.

“My plan was just to be in the lab to learn a bit about what goes on there, not to become a lab investigator,” he said. “But I really enjoyed it. In fact, it became all I could think about—the hypotheses, the experiments—and I realized this was really what I wanted to do.”

Fifteen years after changing his career path, Cohen has no question that he made the right decision. “I would have liked to have spent more time with family,” he said, “but on the other hand, I’ve been blessed with finding a career where I wake up every day and look forward to going to work. It’s never felt like a sacrifice along the way.”

Beth Fand Incollingo is a New Jersey-based writer and editor, and owner of the communications firm Texterity, LLC.