A Translational Scientist’s Guide to World-Class Collaboration

Luis A. Diaz Jr, MD

As the head of the Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center (MSK), the Grayer Family Chair, a cancer genetics researcher, and a mentor to young oncologists and scientists, Luis A. Diaz Jr, MD, has worn many hats throughout his success-filled career of translational research and oncology care.“

Being a translational physician is always tough because no one knows [how to categorize you],” Diaz said. “Are you a lab person, are you a clinician, or are you right in the middle? Everyone thinks you aren’t very good at any [of the above] since you are floating among all of them. It takes a long time to evolve into [someone] of substance, and it takes a lot of hard work.”

Diaz has dedicated much of the past 25 years to both patients and colleagues, as well as to his continued research to improve and extend the lives of cancer patients all over the world. This hard work is reflected among Diaz’s numerous successes as an accomplished physician and pioneer in the space.

Despite his long and successful career as a clinician, Diaz always knew that his heart was in the laboratory. “I remember feeling like a weirdo back in college. I [would] spend nights and weekends in the labs. Even when friends would celebrate after an exam, I would go right back to the laboratory,” Diaz recalled.

Prior to beginning his journey as a renowned investigator, Diaz attended the University of Michigan and the University of Michigan Medical School to earn his bachelor’s degree in microbiology and his medical degree. By 1998, he was a resident at the Johns Hopkins University School of Medicine in Baltimore, Maryland, and well on his way to changing the treatment landscape with his transformative discoveries.

Diaz and Andrea Cercek, MD, with from left, patients Sascha Roth, Imtiaz Hussain, Avery Holmes, and Nisha Varughese. Diaz’s immunotherapy research informed Cercek’s trial exploring dostarlimab (Jemperli), which cured rectal tumors in these 4 patients.

At the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Diaz met mentors who would shape the way he looked at patients and the future of cancer treatment, among them Charles Wiener, MD; David Hellmann, MD; Kenneth W. Kenzler, PhD; Ross C. Donehower, MD; and Bert Vogelstein, MD, the Giants of Cancer Care®award winner for gastrointestinal cancer in 2013. Diaz calls such mentors his “heroes.” When he thinks about the tremendous influence they have had in their respective oncology fields, and on his professional life, he compares it to meeting a superstar athlete.

“It was interesting growing up in an academic environment and finding like-minded people. When I meet my mentors, I remember that these people, much like sports players are to other people, are my heroes,” Diaz said. “These are people whose papers I read and who I got inspiration from.”

World-Class Ideas

Diaz became a mentor himself in 2016 when he was named head of the Division of Solid Tumor Oncology at MSK. He is quick to acknowledge that he has benefited from the work done by scientists who came before him. At the same time, he takes pain to share credit for his own success with other experts and scientists.

“[Whether I was] a member or a leader, teams have gotten me through really tough times. One constant of all the teams I have been involved with is that we are always trying to do something special, something first, something that is magic,” he said.

Diaz spearheaded the landmark proof-of-principle study demonstrating that pembrolizumab (Keytruda) induced durable responses in patients with metastatic, microsatellite instability–high (MSI-H) or mismatch repair deficient (MMRd) colorectal cancer (CRC) tumors that have progressed following prior treatment. It was the first time that patients with CRC responded to an immune checkpoint inhibitor. The FDA issued an accelerated approval for pembrolizumab as the first tumor-agnostic agent for patients with MSI-H or MMRd tumors.

“As a physician-scientist, Dr Diaz has transformed the field of early cancer detection and screening with his innovative science and think-outside-the-box approach,” said Yelena Y. Janjigian, MD, chief of the gastrointestinal oncology service at MSK. “His discovery that MSI-H tumors can be cured with immunotherapy changed practice and the lives of countless individuals worldwide. Therefore, the Translational Science category is the most appropriate, [but he has] transformed the field of cancer on so many levels.”

Diaz spearheaded this world-renowned and landscape-changing trial initially while he was at Johns Hopkins University, and then continued it as he began his new positions at MSK. As he adapted to MSK, it took Diaz little time to involve those around him in the magic-making that he refers to as research.

Diaz chats with a patient at MSK. Michael Foote, MD, a medical oncologist at MSKCC, calls Diaz “one of the most brilliant, creative, caring, people I have ever met.”

Michael Foote, MD, an MSK medical oncologist, first became acquainted with Diaz during their time together at Johns Hopkins School of Medicine in 2012. Foote knew he wanted to join Diaz’s laboratory noting that the senior investigator was kind, generous, and welcoming from the get-go. “Right away, I was blown away by Dr Diaz’s cutting-edge and future-leaning research program. He is truly one of the most brilliant, creative, and caring people I have ever met,” Foote noted, adding that, “Dr Diaz challenges all of his protégés to find the opportunity in your research project to transcend it from a good project to a ‘world-class’ idea.”

Diaz helped to lift a good idea into a world-class idea in 2013 with the development of a molecular Papanicolaou (Pap) test. This test detects early-stage ovarian and endometrial cancers based on genetic markers in cervical cells, revolutionizing the care and treatment of patients.

Diaz and colleagues hypothesized that a simple standard Pap test could be conducted during a routine examination to detect DNA from most endometrial cancers and a fraction of ovarian cancers—and they were correct. So far, the test has helped detect ovarian and endometrial cancers in thousands of patients.

Foote, who currently works with Diaz on his MSK team, continues to incorporate Diaz’s forward-thinking attitude into his own way of practicing medicine.

“Dr Diaz doesn’t see the world as it is; he sees what it could be,” Foote added. “His perspective of medical science looks 10-plus years beyond what other scientists evaluate, and he pushes his mentees to also think toward the future.”

By imbuing this vital mindset in up-and-coming scientists, Diaz continues to exemplify what it means to be a translational researcher, motivated to do right by the patients who need these medications and therapies now. He combines this sense of urgency with an equal part of caring.

In 2008, Diaz helped lead the research that resulted in a major finding: that detection of circulating tumor DNA following a patient’s resection of their stage II colon cancer would help clinicians identify patients at high risk of recurrence and make better-informed decisions regarding adjuvant treatment.

“Dr Diaz is the epitome of a cancer giant,” Foote said. “His footprint has changed every aspect of oncology: from basic science discoveries to clinical and translational trials, and finally to being a role model for the perfect patient-centered doctor.”

Changing the Facets of Treatment

Despite his many successes, Diaz continues to find time for those around him. As a mentor, he believes in investing in others and stressing the importance of teamwork.

“Aside from his visionary thinking about cancer care and science, he is an outstanding mentor and natural leader. He recognizes the hidden potential within people and is able to cultivate it, inspiring and pushing individuals to achieve and to dream bigger,” Janjigian said.

Diaz with MSKCC colleague Yelena Y. Janjigian, MD, left, and MJH Life Sciences^® executive vice president Donna Short at the 2022 Giants of Cancer Care^® awards ceremony.

In addition to serving selflessly as a mentor, Diaz is now giving back on a national level: He was appointed in 2021 as one of 7 members of President Joseph R. Biden’s National Cancer Advisory Board.

Advisory board members play a vital role in guiding the National Cancer Institute, which in turn acts as a lead to the oncology community at large. Board decisions affect millions of physicians, investigators, and patients and families across the United States.

“I truly believe that hundreds of thousands of patients are alive today because of Dr Diaz, and his impact will spread through cancer research for the next century,” Foote said.

Diaz continues to change the treatment landscape for patients with practice-shifting data and research. He recently led a 12-patient phase 2 trial that resulted in a clinical complete response rate of 100% in patients with locally advanced, MMRD rectal cancer, utilizing single-agent dostarlimab-gxly (Jemperli). The results drew worldwide attention both in and out of the oncology community, including in mainstream news outlets such as The New York Times and CNN.

With countless wins and recognitions under his belt, Diaz continues to dedicate these victories to those around him, including his mentors, protégés, and peers. It is because of them, Diaz said, that he continues to move forward.

“We owe it to [our protégés] to push forward and learn from them just as much as we have taught them,” Diaz said.