From Mexico City to the Heights of Leukemia Medicine

If the name of leukemia specialist Jorge Cortes, MD, appears any more often in PubMed, they’ll need to name a wing after him. 
Over 30 years, Cortes has led or co-authored hundreds of studies, including many trials of landmark drugs to treat chronic myeloid leukemia (CML). His work has helped transform CML into an often-survivable disease instead of one that took the lives of most patients within 5 years.
“It’s been remarkable to see the evolution in CML and to be part of that transition as a fellow, as faculty, and as leader of some of the trials,” said Cortes, who directs the Georgia Cancer Center at Augusta University, Augusta, Georgia. “I’m the luckiest person in the world.”
In an interview, Cortes talked about his youth in Mexico, his research path, and his close connections to cancer medicine in Latin America.
Q: You grew up in Mexico City. What was your family like?
A: “My father grew up very poor in a small town in Michoacán in the southwest part of Mexico. In Mexico City, he had a tiny grocery store in an old-fashioned market, and we were lower middle class.
One of the things I learned was to work hard. There’s nobody I know who worked as hard as my father. He opened his store every day of the year, [Mexican] Independence Day or New Year’s or Christmas. He worked hard so we could have a better life than he did.
We learned English from a very young age. My elementary school was called Westminster School because he wanted a school where we would learn English.
As for my mother, she stayed with us [at home] and made sure we did our homework and were taken care of. I learned about being honest and dedicating to what you were doing.”
Q: You trained at the Salvador Zubirán National Institute of Health Sciences and Nutrition in Mexico City. Then what happened? 
A: “Through encouragement by my dermatologist older brother and a mentor at the institution where I was training as a hematologist, I decided to come to the United States.
My initial focus was going to be on coagulation and thrombosis. I came to Houston (Texas) for a fellowship at the University of Texas Health Science Center.
Then I started doing my rotation for the malignant part of the fellowship at MD Anderson Cancer Center [Houston]. One of my first rotations was with Susan O’Brien, [MD,] who became my greatest mentor throughout my career. I really enjoyed my rotation. I thought she was great clinically, and she was doing research and teaching. That’s what I wanted for my career.”
Q: What drew you to leukemia specifically?
A: “Dr O’Brien worked in leukemia during my initial rotation, and I really loved it. It was hard work, but it was very inspiring to see the clinical research and the things you could for patients. She had a lot of joy doing that. 
I told my program director I’d change and transfer to MD Anderson, and I ended up staying at MD Anderson for 23 years.”
Q: What was leukemia research like in those days?
A: “We didn’t have the understanding of the biology and the new drugs that we have now. When I started in Mexico, we didn’t even have hydroxyurea. What we were doing was much more basic. But still, the field sounded like a great field to be involved with because they were doing so many trials and had an outstanding database. 
Because of the influence of Dr [Moshe] Talpaz, [MD,] I started getting very involved with CML. In my initial years as a young faculty, I started working with him on interferon. Then imatinib appeared. I saw even from the phase 1 study how impressive the outcomes were in patients who had no response to anything and were in bad shape.”
Q: What CML medications have you worked on?
A: “I’ve been involved with all of them. Imatinib early on, then I led trials with dasatinib and nilotinib. Then, I led the registration trials of bosutinib and ponatinib. More recently, I was part of the development of asciminib.”
Q: What were some of the biggest challenges in CML research?
A: “We had an opportunity to do a lot of analysis about TKIs [tyrosine kinase inhibitors] when these were new drugs. It was a very steep curve of learning, how to monitor and manage side effects.
Then patients were starting to have resistance to two to three TKIs. Ponatinib came along, and it was an incredibly effective drug. But after it was approved, we started to recognize the occurrence of heart attacks and strokes.
That was unexpected and not something that was known for any TKI. It was a big challenge. The drug was taken off the market for some time, and trials were put on hold by the FDA [US Food and Drug Administration].
We scrambled to understand the mechanism of action. For a year or two, it was a stressful time. But eventually we moved past it, and we learned a lot.”
Q: What sort of work have you done in Latin America?
A: “I’ve always been very close to Latin America. I have many good friends and colleagues there, and I’ve always been interested in working with them. 
We’ve done research and studies and created an organization called Latin American Leukemia Net to develop more trials in Latin America. The most rewarding thing has been the educational programs for patients that we’ve done, helping them understand the disease, the treatments, and the goals of treatment. 
We’ve conducted a number of programs, and they have been effective, well-attended, and well received. I still work with my colleagues to develop local guidelines and do collaborative research.”
Q: What convinced you to leave MD Anderson for Georgia?
A: “I never thought I’d leave MD Anderson. I had my well-oiled machine of clinical trials, my clinic, and my fellowship program. But the one thing that I wanted to see if I could try next was to develop an institution.
That was the goal here, to take the Georgia Cancer Center to NCI [National Cancer Institute] designation. So, I thought, ‘That’s a nice challenge.’ It may be a good opportunity to try a different aspect of what it means to be an oncologist.
There are days that you think, ‘What am I doing here?’ when you have to deal with budgets and personnel and all these things. But it’s part of the process. It’s still good to know that we have a goal, and that we’re going to make it. 
Also, I still see my patients, and I enjoy that I still do some research and mentoring.”
Q: What’s the current state of CML treatment?
A: “Many patients have a pretty much normal life expectancy while [on therapy]. Still, one of the goals of many patients is to stop therapy. But that’s a reality only for a small percentage of patients. How can we make that happen for more patients?”
Q: By stopping therapy, do you mean curing the cancer?
A: “Yes, pretty much. You have a good response, you stop the therapy, and it doesn’t come back.
There are also patients who really don’t do well. We hear about CML being with a disease with such a good outcome, but we have patients for whom nothing works. Is it a matter of [needing] another TKI, or do we need to look at something else?”
Q: What do you see on the horizon?
A: “We are developing new approaches like combination therapies. We’re scratching the surface on that. We need to understand which combinations work, and where and when.
And we can make more efficient uses of the drugs we have now in terms of which ones to use when, the doses, the safety profiles. I think we can do better.”
Cortes disclosed consulting for Amphivena, Astellas, Bio-Path, BioLineRx, Bristol Myers Squibb, Daiichi Sankyo, Jazz, Novartis, Pfizer, and Takeda and research funding from Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo, Immunogen, Jazz, Merus, Novartis, Pfizer, Sun Pharma, Takeda, Tolero and Trovagene.
Randy Dotinga is an independent writer and board member of the Association of Health Care Journalists.
 
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