Pursuing an Ethic of Service: Lung Cancer Researcher Noted for Drug Discovery, Charitable Works

Mark G. Kris, MD

What would you do if you had only one year to live?

For most people, that’s a hypothetical question, a playful way to consider what’s really meaningful in life. For Mark G. Kris’ patients, the dilemma is nearly always reality—and their typical answer is not what many might expect.

“People have the idea that, if they were told they had a serious illness, they’d quit their job, take a cruise, and move to Bora Bora,” said the renowned physician and researcher who specializes in thoracic cancers. “That’s hogwash. People want to experience those things they think are important—usually family, home, and pets. They want their life to go on, even if it’s radically changed, if they can still enjoy the things that are important to them.”

Kris, who is chief of the Thoracic Oncology Service and an attending physician at Memorial Sloan-Kettering Cancer Center (MSKCC) as well as a professor of Medicine at Weill Cornell Medical College in New York City, has dedicated the past 30 years to helping patients meet that goal.

The 60-year-old lifelong New Yorker conducts clinical research focused around the development of biologically based treatments that attack lung cancer, tests for new anticancer treatments, and therapies that combine surgery, radiotherapy, and chemotherapy.

Specifically, Kris conducted clinical trials as part of the development of gefitinib (Iressa), an epidermal growth factor receptor inhibitor that the FDA approved in 2003 for patients with advanced non-small cell lung cancer. His team at MSKCC was the first to notice that some patients with that disease who had exhausted all other treatment options responded dramatically well to Iressa. The same year the drug was approved, Kris said, the team was among those who discovered the mutations that caused sensitivity to the drug.

More recently, Kris helped bring about the FDA’s August 2011 approval of crizotinib (Xalkori), a drug for patients with late-stage non-small cell lung cancer who have mutations in the anaplastic lymphoma kinase (ALK) gene. During its development, Kris advised Pfizer Inc and treated clinical trial participants with the drug, which was approved along with a diagnostic test to determine whether patients have the ALK mutation. Because of Xalkori, Kris said, an additional 10,000 cases of lung cancer each year will be treatable.

Kris believes an additional 10,000 cases of lung cancer each year will be treatable because of crizotinib, which he helped develop.

Throughout his career, Kris has remained committed to treating the whole patient. That has translated into an ongoing effort to develop drugs to control nausea caused by cancer treatment. Toward that goal, Kris was involved in the testing on humans of drugs that had been developed for other purposes, including agents that block the seratonin receptor, steroids, and aprepitant. As combination therapy, such medications have been successful in controlling the debilitating emesis that once haunted lung cancer patients treated with medications such as cisplatin.

While the doctor is still deeply troubled by the lack of widely successful curative measures for people with lung cancer, he recognizes that his contributions have helped bring about an enormous change in the patient experience.

“I lost a patient recently after three years of metastatic lung cancer, and the sad thing is he was lost,” Kris said. “But his first time in the hospital was in the days before his death. When I began in this field, every patient was in the hospital to get treatment, for complications of treatment, over and over again. The disruption of your life was so much more, and the average length of life has expanded tremendously, from months to years. It’s been a very dramatic change.”

How Role Models Shaped Career

It’s really no surprise that Kris found his way from his childhood in Buffalo, New York, to a career in oncology.

The youngster who excelled in chemistry and biology was exposed to the field when his father, a chemist, and his mother, a nurse, took jobs in a cancer hospital. His perspective was also shaped by his years at a high school run by the Jesuits, an order of Catholic priests.

“Their message is that service to others is incredibly important, and that that needs to be part of your life,” said Kris, who recently won a Humanitarian Award— the first ever given by the American Society of Clinical Oncology (ASCO)—for his work as a volunteer helping victims of natural disasters, including hurricanes Rita and Katrina.

Mark G. Kris, MD, At A Glance

Volunteering to raise funds for lung cancer research is an important undertaking for Kris.

• Is married and has 2 children: a 26-year-old son who works as a diplomat with the US Foreign Service in Dubai, and a 29-year-old daughter who teaches in the New York City public schools.
• Enjoys running and taking photographs in his leisure time. He has run in marathons as part of Fred’s Team, whose members compete in endurance events around the world to raise funds for research at Memorial Sloan-Kettering Cancer Center.
• Lists his status as an Eagle Scout, dating back to 1965, on his curriculum vitae.
• Enjoyed the book The Making of the Atomic Bomb, which he describes as “just an extraordinary story of science, politics, and humanity played out on a world stage, perhaps never to be repeated again.”
• Accepts that life is unavoidably difficult, and moves forward from there. “I deal only with folks with lung cancer, and most have an extent of lung cancer that cannot be cured by any kind of current treatments. It’s a deadly disease, and you can’t get around that,” he said. “What’s important is to maintain hope and forward movement without being focused on the challenge or the end, but rather on what is doable now and what is most important to the patient.”
• Is conducting his research with the help of major grants from the National Institutes of Health, the National Cancer Institute, and Stand Up to Cancer, a project of the Entertainment Industry Foundation that utilizes the star power of celebrities to raise funds aimed at slowing the competition between labs and bringing them together to collaborate. Kris serves as a Dream Team principal within the organization.
• Continually volunteers to help poverty and disaster victims in the United States and abroad through activities such as rebuilding homes. “It’s extremely rewarding, extremely educational, and you learn so much about other ways of life,” he said. “It makes you stop and appreciate the things you have and how fragile they are, how in an instant they can be gone.”
• Was honored last year with ASCO’s first-ever Humanitarian Award, and also won the 2010 ASCO Statesman Award and the organization’s 1989 Career Development Award. He received the HealthCare Chaplaincy’s 2011 Wholeness of Life Award, which honored “healthcare professionals who recognize and tend to the whole person—spirit, mind, and body.”

Kris went off to Fordham University knowing he wanted to become a doctor, and he took “a zillion” science courses. But the summa cum laude graduate majored in English.

“I liked reading and writing, and that’s been a great help, actually, in medicine,” said Kris, who for 7 years served as a member of ASCO’s Patient Communication Subcommittee. “Communication and writing are absolutely critical to success in every career, and medicine’s no exception.”

Heading for Weill Cornell University Medical College, Kris had the idea that he would become a gynecologist. The specialty offers opportunities to perform surgery, deliver babies, and “be a doctor to people, to try to keep people healthy,” Kris said. “There were also great strides there to protect women from cervical cancer.”

But the doctor later opted for oncology, appreciating the challenge of the relatively young field, as well as the unmet need involved.

After earning his medical degree in 1977, Kris completed an internship and a residency in internal medicine at New York Hospital in New York City, which is associated with Weill Cornell. He signed on at MSKCC as a fellow in medical oncology after the staff members who interviewed him for the position won him over.

“I came here and interviewed with a faculty member, and he thought I was some kind of asset, so he pulled in the chair of the medical department, whom I’d never met before,” Kris remembered. “No one else had their chair come into the room specifically wanting to shake my hand, and that meant something.”

The young doctor showed up for the job thinking he would specialize in leukemia, but that goal changed, too.

“My first job at Sloan was in the developmental chemo service, where we tested brand-new medications,” Kris said. “Because there was no treatment for metastatic lung cancer back then, any person who came to Sloan and had it got referred to this experimental group, and we’d give them whatever experimental drug we had to test in hopes of finding a treatment.”

Convinced that he had found the specialty where his help was needed most, Kris stayed in lung cancer. The grim prognosis for most of his patients did not give him pause.

“Everybody has the potential to die, or dies,” he said. “It’s like life— everybody dies, but it’s the journey, and it’s a good journey.”

Finding a Home at MSKCC

Kris has never regretted his decision to join the staff at MSKCC, where he moved up through several attending physician positions before becoming chief of the Thoracic Oncology Service in 1990. The doctor, who also serves as the William and Joy Ruane Chair in Thoracic Oncology, has always felt in his element at MSKCC, where everyone speaks the language of oncology and understands its nuances.

“The people who work here are pretty extraordinary,” Kris said. “They don’t end up here—they choose to work here, and that goes for everyone, including professional and nonprofessional staff. People get turned on and dedicated here. For example, there was a nursing shortage a few years ago, and the hospital decided to encourage, and pay for, our own staff to go to nursing school. Two hundred of our people who work in offices and patient-care areas went, and a large proportion of them want to continue working here when they’re done. That speaks a lot to the staff here.”

Kris supports the use of CT scans to screen people at high risk for developing lung cancer, a group that includes older smokers and former smokers. “There are 8 million people in America who fit those criteria and they all should be screened today,” he said. “Period.”

Kris spends about 40% of his time on the job treating patients, many of whom are participants in his research, for conditions including lung cancer, thymoma, mediastinal tumors, and cancer of unknown primary site. He dedicates another 40% of his hours to supervisory duties and research, which involves taking the discoveries of laboratory scientists and moving them into clinical trials, which he “constantly” designs and leads.

Kris spends another 10% of his time teaching doctors who are developing a subspecialty in oncology after finishing their training as internists. On the other end of the spectrum, Kris trains those who have just started medical school.

“They come to me with a simple goal: to be able to walk into the room with a patient and have a comfortable conversation—the rudiments of acting like a doctor,” Kris said.

Kris gives the remainder of his working hours to traveling the globe to lecture, conduct grand rounds, and meet with pharmaceutical companies about compounds they’re developing.

Lumped in with that work outside the hospital are Kris’ efforts on behalf of ASCO, where he helps to organize the annual meeting and to develop guidelines, and with the National Comprehensive Center Network.

Recently, Kris has been a driving force in making sure that doctors, through international oncologic standards, are encouraged to test newly diagnosed lung cancer patients for specific mutations, in an effort to help determine which treatments are likely to work best for them.

“By doing that, and doing it right, I have the opportunity to influence the care of every cancer patient on earth,” Kris said. “It’s pretty amazing, actually.”

Supports Clinical Trial Changes, and CT Scans for Lung Patients

Within ASCO, Kris has been involved in drafting another set of guidelines, called the Blueprint for Transforming Clinical and Translational Cancer Research, released in November 2011. Changes are badly needed, he said, because the clinical trials process is “broken.”

Mark G. Kris, MD, Research Snapshot

Q: What is the thrust of your most current work?

A: My main interest at the moment is ensuring that the tumors of lung cancer patients are tested for specific mutations at the time of diagnosis, so that doctors can use that information to choose the best treatments. Since it began in the fall of 2009, I’ve been one of the leaders of the Lung Cancer Mutation Consortium, which brought together 14 American academic centers that shared a common idea: that a disease that had one name, lung adenocarcinoma, was heterogeneous—that patients had different responses to therapy, and that a decade of research showed that the differences could be explained by the genetic lesions underlying the tumors in each patient. The rationale was that understanding the biology of a tumor could lead to better choices of therapy.

Q: How was the consortium created?

A: Led by Dr Paul A. Bunn, Jr, the consortium came about as a result of the American Recovery and Relief Act of 2009, through a Grand Opportunities grant.

Q: What were the consortium’s initial goals, and what were its outcomes?

A: Our goal was to test 1000 tumor specimens from patients with lung adenocarcinoma for the 10 known driver mutations: KRAS, EGFR, BRAF, HER2, PIK3CA, AKT1, NRAS, MEK1, EML4-ALK, and MET amplification. We planned to use these in real time to select erlotinib for patients with EGFR mutations and, for patients with other mutations, to recommend trials of agents targeting the mutations we found. So, we did it. We detected an actionable mutation in 54% of individuals with lung adenocarcinoma, and we used this information in real time to select erlotinib as an initial therapy for some patients and to direct others to clinical trials.

Another important goal was to develop a testing capability at each site. Among our 14 institutions, four had testing up and running at the start. Now, 11 have some testing open. Our goal was achieved in that, at each institution, after the life of the grant, testing will continue.

A final goal was to link trials to the mutations we found. Today, we have eight trials linked to the Lung Cancer Mutation Consortium. We didn’t organize the trials, but we affiliated ourselves with ongoing industry trials.

Q: Down the road, are there any further developments you’d like to see come out of the consortium’s work?

A: I hope this will serve as a model for other institutions developing similar programs in lung and other cancers.

Inefficient because it relies on paperwork rather than computerized tracking, the trials process also focuses too much on a “one-size-fits-all drug development paradigm, particularly with regulatory agencies’ rules on how to collect side-effect information,” Kris said.

Kris believes oncologic drugs should not have to meet the same standards as other new medications when it comes to the level of risk for patients.

“When you’re developing a medication where the current standard of care kills five out of every hundred people and the illness itself kills the rest one or two years later, you can’t have the same standards,” he said. “You need to take the disease, and the willingness of the patient, into account.”

Kris added that there should be worldwide standards specifically for oncology medications, so that drug developers do not have to meet a variety of requirements, and timelines, in different countries.

“It involves the agreement of every country on earth, and I don’t think we agree on what time it is,” he said, “but we have to find ways to streamline this process.”

Somewhere close on the horizon, Kris also hopes to see an era where every older smoker or former smoker—a group with a high risk of developing lung cancer—will be screened for the disease, before symptoms appear, via a lowdose spiral, or helical, computed tomography scan.

“There are 8 million people in America who fit those criteria,” he said, “and they all should be screened today. Period.”

Although lung cancer is sometimes stigmatized as a “smoker’s disease,” and Kris doesn’t deny that characterization, he disagrees with those who argue that funding should be used strictly on smoking avoidance or cessation measures, rather than on treatment.

Kris estimates that 15% of people diagnosed with lung cancer—roughly 25,000 Americans every year— have never smoked. “That’s as many as have ovarian cancer or brain tumors or stomach cancer,” he said. “Of the other 85% who get the disease, the vast number have already stopped smoking, sometimes 20 or 30 years ago. The slowdown in smoking is great for the next generation, but it doesn’t help this one. We need better treatments for lung cancer, and we will need them through my professional lifetime and probably longer—especially because 40 million Americans still smoke.”

Remaining part of the solution will be a pleasure, as his work has always been, Kris said.

“I’ve been privileged every step of the way,” the doctor said. “I’ve heard people say that, if you choose the right profession or job, you’ll never have to work a day in your life, and I feel like that.”