Cancer Researcher and Drug Developer, Joseph R. Bertino, MD, Dies at 91

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Joseph R. Bertino, MD

Joseph R. Bertino, MD

Over the arc of his notable career, Joseph R. Bertino, MD, garnered many honors for his scientific contributions leading to curative treatments for leukemia and lymphoma, such as ASCO’s David A. Karnofsky Award. Yet his legacy was perhaps most prominently punctuated by the multitude of patients with cancer who benefited from his dedication and wisdom as a physician-scientist, whose work contributed to the foundation of modern cancer research. Dr. Bertino died on October 11, 2021, at the age of 91.

Son of Immigrants

Dr. Bertino was born in Port Chester, New York, the youngest of three sons born to Joseph and Mamie Bertino, immigrants who arrived from Italy shortly after World War I. Although he showed early acumen for chemistry and biology in high school, he attributed tacit pressure from his proud immigrant parents to become a doctor, a family first, as his impetus to attend Cornell University, where he committed himself to a career in medicine.

After receiving his undergraduate degree from Cornell, he attended medical school at SUNY Downstate College of Medicine, attaining his medical degree in 1954. Bent on a career in oncology, Dr. Bertino did a U.S. Public Health Services fellowship in hematology and oncology at the University of Washington School of Medicine.

Passion for Research

It was at this time that Dr. Bertino’s passion for research fully emerged, and in 1958, he relocated to Seattle to work with Drs. Clement A. Finch and Frank M. Huennekens. It proved to be an invaluable career move, as it was Dr. Huennekens’ groundbreaking work in folate metabolism that inspired Dr. Bertino’s understanding of how methotrexate worked, which would prove pivotal in his later research.

About 3 years later, Dr. Bertino accepted a joint appointment in the Department of Pharmacology and Medicine at Yale University School of Medicine. In 1973, Dr. Bertino became the first Director of the Yale Cancer Center; although he would remain at Yale, he resigned his directorship in 1975, when he was named an American Cancer Society Research Professor. It was a busy year, as Dr. Bertino was also elected President of ASCO.

Many top researchers make note of an ah-ha moment, and for Dr. Bertino, it came during a sabbatical in 1976 while studying methotrexate resistance with Drs. Robert T. Schimke, Rod Kellems, and Frederick W. Alt. “We knew that when cancer cells became resistant to methotrexate, the proteins on the cell increased, and there was more ‘message’ being delivered to the cells telling them to block the drug from doing its job in attacking the cancer. We wondered how this was occurring. Using laboratory models, we found that cells had the ability to multiply genes that were coded for the target for methotrexate, a protein called dihydrofolate reductase. This finding was eye-opening in that everyone thought DNA was very stable. Discovering this mechanism was important because of its ability to trigger resistance to anticancer drugs and its ability to increase levels of oncogenes that contribute to cancer,” said Dr. Bertino.

Joins MSK

Dr. Bertino left Yale in 1987 to become Head of Developmental Therapy and Clinical Investigation at Memorial Sloan Kettering Cancer Center (MSK). At MSK, he contributed important papers on drug resistance in leukemia and soft-tissue sarcomas. And during the past 6 years, Dr. Bertino established a translational research laboratory at the Robert Wood Johnson School of Medicine, New Brunswick, New Jersey, becoming Acting Director of its Cancer Center, with the departure of his close friend and former student William N. Hait, MD, PhD. He was continuously funded by the National Cancer Institute for more than 4 decades.

His friend and colleague Bruce Chabner, MD, wrote: “My dear friend and mentor, Joseph R. Bertino, MD, remained active in his laboratory until the last days of his struggle, as one would expect, knowing his passionate commitment to research. I worked as a fellow in Joe Bertino’s laboratory at Yale, an experience that led to a lifelong friendship, scientific collaborations, and my great appreciation for his contributions to oncology.”

Dr. Chabner also noted that Dr. Bertino was a standout athlete, with a fiercely competitive spirit. Reflecting on his friend, Dr. Chabner related: “Joe was a talented collegiate basketball player in the era of 6-foot 2-inch centers. He later turned his attention to softball, tennis, and golf. His weekly tennis matches with Paul Marks at MSK were legendary for their intensity and skill, and continued for many years, although no one but they knew the final score. For the past 20 years, Joe and I shared memorable moments on the magnificent Yale golf course, including close brushes with victory in the annual Beinecke Invitational tournament. Joe was the very best chipper and putter in the amateur ranks.”

Joins a Former Fellow

In 2002, a former fellow at Yale University, Dr. Hait invited Dr. Bertino to join him as Associate Director, an offer he accepted with alacrity. After settling in, Dr. Bertino focused his research on new drug development for solid tumors, especially prostate and small cell lung cancers. His later investigation would look at new targets for T-cell lymphoma and the rare subtype B-cell lymphoma called double-hit lymphoma.

Founder of JCO

Along with his major accomplishments in the lab and clinic, Dr. Bertino also left his mark on the literature as founding Editor-in-Chief of the Journal of Clinical Oncology (JCO), where he was remembered as as inspirational teacher and collaborator who has guided many of the current leaders in the field of cancer research.

Upon the news of Dr. Bertino’s death, ASCO Chief Executive Officer Clifford A. Hudis, MD, FACP, FASCO, said: “Dr. Bertino did it all—major scientific discoveries, organization and professional leadership, teaching, and clinical care—with a rare grace and dignity. He made everyone feel respected and motivated everyone to contribute their best.”

For the remainder of his career, Dr. Bertino continued to be optimistic about the field he devoted his life to: “I wouldn’t change a thing, and I’ve been fortunate to have worked with so many talented colleagues, mentors, and students throughout the years. There is every indication that we will continue to move forward with the development of novel treatments and combination therapies, which will be made much more effective.”