Global Leader in Drug Development John L. Marshall, MD, Calls for a Smarter War on Cancer


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John L. Marshall, MD

When I offer a clinical trial to a patient, I am hopeful that it will lead to better than the standard of care. Health-care reform should not simply provide everyone with insurance to cover standard of care, but should also force us to determine the true value of treatments. And in doing so, it will force us to fight a smarter war on cancer.

—John L. Marshall, MD

John L. Marshall, MD, a global leader in the research and treatment of gastrointestinal cancers, grew up in Lexington, Kentucky, in a family that put high value on education. As a young boy, science was already on his mind; he enjoyed the explorative nature that chemistry and biology offered. However, his introduction to oncology came too soon. “When I was kid, my mother developed non-Hodgkin lymphoma. After school I’d go with her to the clinic, where I witnessed radiation and chemotherapy and the terrors associated with many of the treatments in those days. She ultimately died after about a 7-year battle with the disease,” said Dr. Marshall.

“I was nearly 14 when my mother died. That’s a tough age, a time of transformation when you struggle between being a kid and an adult. After that kind of trauma, a kid can lose himself in anger or charge ahead. I chose to charge ahead and become a doctor,” said Dr. Marshall.

Relishing the Role of an Outsider

It was a time when M*A*S*H was the most popular show on TV. Offbeat martini-drinking surgeons of the 4077th Mobile Army Surgical Hospital cared for the wounded during the Korean War. “I was always the cutup in class, so I identified with the character ‘Hawkeye’ in M*A*S*H. That’s who I modeled myself after: a good doc with an irreverent, mischievous personality. I still bring those qualities to my lectures and into the clinic,” said Dr. Marshall.

Dr. Marshall left Kentucky and went to a boarding school in Washington, DC. After graduating boarding school, Dr. Marshall went to Duke University, where he obtained a BS degree in psychology in 1982. He then returned to his home state, entering the University of Louisville School of Medicine; he received his MD degree in 1988.

“One good thing about going to school in Kentucky is that you’re almost certain to have at least one team in the NCAA final four. That perk aside, I left Kentucky and did my internship at Georgetown University Medical Center, completing that in 1989 and staying at Georgetown for my residency in internal medicine,” said Dr. Marshall.

“I loved the atmosphere at Georgetown, so after my internship, I decided to stay. I’m currently Chief of the university’s Hematology/Oncology Division. My focus is on new drug development. I’ve joked in the past that I grew up in the 1970s, so I’ve been testing new drugs for a long time, and now I’m choosing to test them on others,” said Dr. Marshall with a laugh.

Dr. Marshall stressed that although much of his energy is focused on developing new therapeutics, unlike many researchers, he does not favor the large randomized trial setting. “I’ve not been a major contributor to the cooperative group structure. Simply put, I’ve always thought that bigger trials yield smaller benefits. And in cancer, we have so far to go that I feel we should be spending our time, energy, and money on more dramatic pathways to discovery,” said Dr. Marshall.

Immunotherapy’s Renaissance

“My longtime subspecialty, if you will, has been in immunotherapy,” said Dr. Marshall. “I pride myself in being one of the few clinicians who explored immunotherapy when it was not taken seriously by the main body of oncology. I remember very distinctly being regarded as somewhat crazy for having such passion over immunetherapy. Other less critical people called me overidealistic for believing in immunotherapy’s potential.”

Due to the embedded pessimism within oncology circles about immunotherapy’s promise, Dr. Marshall struggled for more than 20 years with grant applications and rallying support and backing for clinical trials. Asked why he and other like-minded researchers faced such opposition, Dr. Marshall replied, “I recently read The Emperor of All Maladies, and it’s clear that in cancer we get ideas about which is the right path to take and we don’t like to deviate. Remember, everything we do is peer-reviewed, and it is a system that totally embraces the current mainstream thought and looks suspiciously at those who may come at a cancer problem from a different angle. Inadvertently, the current system has a way of stifling innovation.”

“We were a small group back then holding up the flame of immunotherapy all the while battling a barrage of negativity. That’s why we are overjoyed that immunotherapy is finally getting the attention it deserves,” he commented.

According to Dr. Marshall, the breaking point for mainstream acceptance of immunotherapy was discovering checkpoint inhibitors. “I think that we’ve finally convinced the skeptics. The growing understanding of the science behind immunotherapy is generating increased interest from the clinical community, and as we get more encouraging results from ongoing studies, I think we will see the ‘bandwagon’ grow,” said Dr. Marshall.

A Smarter War on Cancer

Although an avowed optimist, Dr. Marshall noted a huge disconnect between patients, the cost of care, and the clinical benefit of cancer treatment. He stressed that cancer medicine is publicly regarded as an area of significant progress, adding many new therapies to the market. However, he added a sobering reminder. “Since 1971, when Richard Nixon declared war on cancer, we’ve spent countless billions of dollars on research, yet we have made only relatively minor progress.”

Dr. Marshall said that in some ways we are collectively waving the white flag and have given up on the idea of trying to win the war on cancer. For example, he cited that few cancer clinical trials are designed to “cure” patients; instead they are aimed at detecting small differences between the treatments being compared. “The oncology research and treatment community should ask itself a simple question: Can we do something different to move the outcomes needle forward?” said Dr. Marshall.

“When we talk about giving patients standard of care we know that it is not going to dramatically improve our outcomes. And I’ve always wondered why our patients haven’t been more aggressive in their own advocacy. There seems to be too much patient acceptance, by both doctors and patients,” said Dr. Marshall. Could he offer a reason for this decades-long passivity? “Well, the short answer is that cancer patients are scared for their lives and will accept what is offered, instead of taking a stand and questioning the established way to deliver care,” said Dr. Marshall.

“A major focus of health-care reform is for doctors to practice true evidence-based medicine and put value over volume of services. When I offer a clinical trial to a patient, I am hopeful that it will lead to better than the standard of care. Health-care reform should not simply provide everyone with insurance to cover standard of care, but should also force us to determine the true value of treatments. And in doing so, it will force us to fight a smarter war on cancer,” said Dr. Marshall.

A New Initiative to Tackle Disparities in Cancer Care

Of the approximately 7 billion people in the world, Dr. Marshall pointed out that less than 1 billion have access to cancer care. “This incredible lack of care is due largely to countries that have resources, but just not enough to support this level of health-care expense. If we in the United States, the world’s richest country, cannot sustain our current spending on cancer, how are we going to develop a model that can deliver cost-effective cancer care to those 6 billion humans who currently have no services?” asked Dr. Marshall. Mulling over that vast existential problem led to his latest initiative: The Gastrointestinal Cancers Alliance Network (GI CAN).

“I see the globalization of cancer care as an opportunity for clinicians to return to our original calling, which is to help the sick. I’m proud to be a member of the newly formed GI CAN, whose central mission is to link the stakeholders back together and develop common processes and systems and big data realms, hoping to shape a more equitable standard of care for the world’s underserved populations,” explained Dr. Marshall.

He continued, “A friend of mine spends about 2 weeks every year of his personal vacation time in sub-Saharan Africa providing basic medical care to people who travel by foot seeking help for a vast array of ailments. Equipped with antibiotics, some pain meds, and solid primary care skills, my friend and his associates truly make a difference in these underserved patients.”

However, Dr. Marshall emphasized that treating cancer patients is far more difficult in low-income countries. “Without access to scanning technologies, palliative care services, surgeons, and chemotherapy, I would have very little to offer a patient seeking help,” said Dr. Marshall. “When dealing with such limited resources, it’s important to develop region-specific guidelines for low-income countries, which will allocate services to those who can benefit from them. It’s a form of cancer care triage, but it’s necessary if we want to expand basic cancer care throughout the world.”

Acknowledging the magnitude of challenge ahead, Dr. Marshall said, “To be effective on a global scale, the alliance will initially focus on gastrointestinal cancers, connecting emerging providers in the developing world to leading cancer care and research institutions.”

Global Collaboration Needed

“We as a community talk a lot about lung cancer, breast cancer, and prostate cancer, but collectively gastrointestinal cancers are the most common and most fatal cancers on the planet. And as a community, we have failed to discover the driving mutations behind these malignancies. Consequently, industry has lost much of its interest in certain gastrointestinal malignancies. In effect, the gastrointestinal community has dug itself into a hole,” said Dr. Marshall.

Coming back to GI CAN, Dr. Marshall said, “To develop effective treatments for gastrointestinal cancers, we need massive information-sharing data sets. No one center or cooperative group or nation has enough patients for this kind of discovery. So, a central part of GI CAN’s effort is to create a platform of collaboration among major academic institutions, IT companies, and the pharmaceutical industry to reduce the cost of clinical trials. We seek to simplify the process and set up a global cancer care infrastructure. And as we find increasingly effective therapies in a more cost-efficient manner, we hope to reach a value point that will be affordable for all people around the world.”

Asked for a closing thought, Dr. Marshall offered, “If I could have one eternal gift for Christmas, I would wish for a Sorting Hat. For those unfamiliar with Harry Potter books, a Sorting Hat is used as a sort of ‘soul biopsy’ for the new kids at Hogwarts School of Witchcraft and Wizardry, which assigns them to one of the four specialty houses. That’s what we really need in oncology. I want an unflawed test that houses my patients and tells me what their future really holds. Then I wouldn’t need the trial-and-error empirical methodology we use today. It would remove the mystery and allow me to make precise decisions.”

He paused a moment and added, “Our obligation and duty is not to try to add just a month or two of survival with a new medicine but to have dramatic impact; patients are expecting us to cure them.” ■


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