Making a Mark in Lung Cancer: An Interview With Roy S. Herbst, MD, PhD

Roy S. Herbst, MD, PhD

When Roy S. Herbst, MD, PhD, looks back on his college days, he does not linger over memories of late-night parties or fraternity pranks.

It is thoughts of the labs where he worked, of mice studies and gene detection, that prompt the oncologist to reminisce.

Those years at Yale University allowed Herbst to explore his curiosity about research and medicine, discover what inspired him, and start defining the path his career would take. Twenty-seven years after completing a combined undergraduate and master’s program there, graduating Phi Beta Kappa and summa cum laude, Herbst has brought the fruits of that experience back to his alma mater.

The physician and translational researcher, whose work in developing novel, personalized therapies for lung cancer has helped drive significant changes in the way the disease is treated, has returned to his old stomping grounds to lead the section of medical oncology at Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven, Connecticut. His mission there is to build a clinical trial infrastructure that will allow Yale to delve further into the study of early drugs and the mechanisms of cancer.

In March, Herbst left a post at the University of Texas MD Anderson Cancer Center in Houston to return to Yale, where he also has been named a professor at the School of Medicine.

“I was enamored by the possibility of taking what I knew—translational cancer research, combination therapies, biomarker and surrogate assays, and understanding how to make the clinical trial a scientific endeavor—and doing it at a place that has a tradition of scientific discovery, yet not in the realm of clinical trials,” said Herbst, 48.

“I’m intrigued to be leading not just lung cancer research, but the entire solid tumor area. And it’s cool to be a professor at the residential college where I was an undergrad, to work with students and inspire them as my professors did me. I love the academic environment at Yale, and I will be an undergraduate advisor this fall,” he said.

Roy S. Herbst, MD, PhD, At a Glance

• Is married and has a 6-year-old daughter
• When he isn’t working, likes to work out and travel
• Is the son of 2 first-generation Americans
• Was shy as a teenager and only later, after working with some of his role models, became comfortable interacting with scientists and patients
• Cites The Emperor of All Maladies: A Biography of Cancer by Siddhartha Mukherjee, as his favorite book (Find out more >>> Interview With Siddhartha Mukherjee, Author of The Emperor of All Maladies)
• In thinking about the fight against cancer, often reflects on a quote from Winston Churchill: “Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning.”
• Is a consultant to companies including Bayer, Eli Lilly and Company, Pfizer Inc, and AstraZeneca
• Volunteers on committees and forums for the Institute of Medicine and the American Association for Cancer Research, whose Tobacco Task Force he chairs. Through smoking cessation efforts, Herbst believes, “I can help more people than I can by treating patients with advanced lung cancer.”
• Has done charitable work for his synagogue and for Aishel House, a Texas nonprofit that provides patients and their families with transportation, meals, accommodations, childcare, and counseling when they are away from home for medical care.
• Has authored more than 200 peer-reviewed papers
• Received awards for excellence at every level of his education, including an award for Distinction in Molecular Biophysics and Biochemistry from Yale University and the Dean’s Research Prize from Cornell Medical College. More recent awards have included the David Ben-Gurion Leadership Award and the Irwin H. Krakoff Award for Excellence in Clinical Research, given by MD Anderson
• Believes that philanthropic funding of cancer research is more important than ever in the face of government budget constraints, and hopes that funders will not overlook hypothesis-based clinical trial research, which can be difficult to quantitate but can lead to the discovery of new molecules or targets

Playing Key Role in BATTLE Trial

Herbst is uniquely prepared for the challenges and opportunities he is taking on as Yale Cancer Center’s chief of medical oncology and associate director for translational research. For the past 14 years, he served as a lab head, clinical researcher, professor, and physician at MD Anderson, making his mark in the area of translational research aimed at finding new and better treatments for metastatic disease—particularly non-small cell lung cancer (NSCLC).

Herbst oversaw some of the earliest phase I studies of agents designed to inhibit tumor metastasis using epidermal growth factor receptor inhibitors or antiangiogenesis agents. Those drugs are now part of the daily clinical armamentarium in oncology, including cetuximab (Erbitux), gefitinib (Iressa), erlotinib (Tarceva), and bevacizumab (Avastin). The doctor’s pioneering work using erlotinib in combination with bevacizumab was among the first to combine multiple molecular—targeted agents for NSCLC.

More recently, Herbst conducted groundbreaking work as co-principal investigator of the Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination, or BATTLE, trial, which involved using biopsies of participants’ tumors to decide which of 4 treatments they would receive. A second phase of the trial, in which combinations of agents are being employed to fight drug resistance, is now underway at both MD Anderson and Yale.

“The BATTLE trial has changed our field in that no one would treat lung cancer now without a biopsy,” Herbst said. “We feel very proud of the fact that we’ve helped make discovery such an important part of lung cancer therapy.”

In fact, Herbst said, the practice of analyzing tumors to identify their markers, and then matching them with the medicines most likely to be effective, will be the protocol for treating all or most cancers.

“We’re beginning to approach an era when the type of tumor won’t matter—only its profile, the genes that drive it,” he said. “That could mean we’ll sometimes use one inhibitor for both prostate and lung cancer, for example.”

In front of the classroom, Weinberg likes to entertain his undergraduates by revealing that he got a “D” in introductory biology, a course he didn’t enjoy when he took it at MIT. And he passes on this wisdom: “Most of the young people in high school have the conviction that biology is all about memorizing facts, when, in fact, it’s a very logical science with a lot of interesting questions that remain unexplored. It’s a very intellectually challenging field.”

Pursuing Collaborative Approach at Yale

Herbst is still settling in at Yale and setting up his new lab, but he anticipates that he’ll spend about 20% of his time at the institution with patients—less than he did at MD Anderson—so that he can reserve time to consider the projects of colleagues, conduct administrative duties within the center, and work closely with its leadership team. Most of his remaining time, another 40%, will be dedicated to doing his own research and writing papers and grants.

Within his busy schedule, Herbst expects to find time to continue lecturing and conducting grand rounds at other institutions around the world. “It’s important that people hear about your work,” he said, “and you learn a lot, too, if you take the time.”

In the classroom, Herbst plans to pass on a handful of principles he considers essential for those in his field.

“I’ll impress on them how important it is to be sensitive to patients,” Herbst said. “We need to care for their physical and emotional needs, to be honest and compassionate at the same time. I also always encourage students to develop a love and excitement for what we’re doing, for the possibilities. I want them to be eager to do better. When you’re in a field where people don’t survive, you have to be constantly looking for new drugs, new targets.”

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We’re beginning to approach an era when the type of tumor won’t matter—only its profile, the genes that drive it. ”

Taking Up a Challenge

Herbst decided to make lung cancer the focus of his career at the suggestion of Emil Frei III, MD, of the Dana-Farber Cancer Institute, regarded as a pillar of modern oncology. Herbst was in his mid-30s and completing a fellowship at the Boston institute at the time. Frei had stepped in as his mentor.

“No one wanted to work in lung cancer because it’s a really tough disease,” Herbst recalled. “Half the patients already have cancer that’s spread.”

Rather than resisting Frei’s challenge, Herbst dove into his work and has risen to the forefront of the field as one of 20 or 30 doctors who have made the disease their primary focus.

Growing up in New Rochelle, New York, Herbst was always interested in becoming a doctor. He credits his mother with passing her scientific ability along to him.

Although she made her career as a school librarian and media specialist, Herbst said, “My mother went to Bronx High School of Science and was very interested in science. She always used to wish she had gone to medical school, but she grew up without the finances or the opportunity to do so.”

Luckily, that door was open to Herbst, whose interest in his field flourished during his time as an undergraduate.

“My real desire to be a physician developed early in my time at Yale,” he said. “I got to work in a lab in the field of neuroscience. I was able to do some animal work, studies of the hypothalamus in mice, and I found it incredibly interesting, so I pursued a combined bachelor’s and master’s degree in molecular biophysics and biochemistry. I also worked in a second lab, one devoted to molecular biology and developing new techniques for gene detection. It was very similar to what I’m doing now as I work in personalized medicine.”

Herbst was already in medical school at Cornell University Medical College—through an elite, government-funded PhD/ MD program at the Rockefeller University, in New York City— when his mother was diagnosed with breast cancer. Shepherding her through her journey to health helped Herbst decide that he wanted to specialize in oncology.

“When a family member has cancer, as a medical student, you don’t have expertise, but you know how to find the right people,” Herbst said. “That’s what medicine is, being a quarterback for a patient. I talked to the different medical experts I knew, and I got my mother access to top pathologists in the field. I did feel that was interesting, and I could see how important oncologic care was and what a difference it could make in a patient’s life.”

Research Snapshot

What is your latest avenue of research?Herbst: My current focus is targeting Ras, an oncogene active in 25 percent of lung cancer patients. No targeted therapy or chemotherapy works against it. We want to target Ras with combined drugs, and will do that in our BATTLE 2 program investigating personalized lung cancer treatment, which was recently funded and will be conducted at both Yale and MD Anderson. I’m very excited about it.

Are you also investigating Ras outside the structure of the BATTLE 2 trial?Herbst: In my lab, I’m trying to target Ras in a number of ways, including looking for some new molecules that might work to inhibit Ras, and screening them. We’re working on animal models, cell lines, and data to suggest that different Ras mutations have differing effects on signaling, and we’re making some very good headway in that direction.

Learning From a Legend

Herbst moved from that idealistic beginning to the top of his field by excelling at some of the nation’s best institutions and working with a handful of its most recognized scientists—including mentor Judah Folkman, MD, who had discovered endostatin and angiostatin, agents that caused tumors to disappear in mice.

Herbst graduated from Rockefeller University in 1990 with a PhD in molecular cell biology and finished medical school a year later. During an internship and residency at Brigham and Women’s Hospital in Boston, a teaching affiliate of Harvard Medical School, he did so well that he was pulled out of the program in his junior year to fill in for a hematology fellow who was unable to work.

“I got experience with clotting disorders, hemophilia, and things you don’t normally see in malignant oncology,” Herbst recalled. “At Yale, which is a general hospital, I see similar things, and I’m glad I’ve had that training.”

Later, Herbst completed an oncology fellowship at Dana-Farber Cancer Institute before returning to Brigham and Women’s for a fellowship in medical hematology. Simultaneously, he completed the HST/Pfizer Clinical Investigator Training Program at Harvard Medical School, something he said helped him “tie together” his study experiences and figure out what to do next.

“I knew I wanted a career in clinical or translational research,” Herbst said. “I didn’t want to go into basic laboratory research, because then I’d have to stop seeing patients to avoid being distracted from my mission.”

Herbst fulfilled that vision at MD Anderson, where he was guided by another mentor, Waun Ki Hong, MD, one of the founders of chemoprevention and now head of cancer medicine at the institution. There Herbst’s research led to an “aha” moment.

“When I was doing the first studies with Iressa, we started to see patients whose metastatic lung cancer tumors melted away,” Herbst said. “I knew we were onto something pretty amazing when I realized we could biopsy tumors and understand their genetic profiles. That woke me up to the fact that this was a future therapy. There was no point going forward giving therapy to patients without matching the right ones with their tumor types.”

Today, that goal helps keep Herbst grounded in the face of the sickness he sees every day.

“I don’t see how I could work in oncology if I wasn’t trying to discover new things,” he said. “Some of the things we treat are so horrible that it’s nice to know we’re trying to offer the most effective new treatments.”

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

Herbst, left, and Gandara share a lighter moment during the congress.

Key Issues, New Research Featured at Lung Conference

The 12th International Lung Cancer Congress, held in August in Carlsbad, California, offered a focused overview and discussion of state-of-the-art care.

Topics included updates on individualized therapies and biomarkers, innovations in radiation therapy, questions about surgical resection, and the debate about computed tomography screenings.

Roy S. Herbst, MD, PhD, and David R. Gandara, MD, director of the Thoracic Oncology Program and a professor of Medicine at the University of California Davis Cancer Center in Sacramento, served as program directors.

The full agenda of virtual presentations and downloadable slides are available free of charge at the OncLive meeting page for the 12th International Lung Cancer Congress.

Watch for the next issue of the magazine for more coverage.