Joseph R. Bertino, a physician who made fundamental discoveries in cancer biology, defined curative cancer treatment regimens, trained generations of influential cancer researchers, ran productive laboratories, and served as the inaugural director of Yale Cancer Center, died on Oct. 10. He was 91.
After Bertino was awarded the 2007 Pinedo Prize at the VU Cancer Center in Amsterdam, his friend and former fellow Bruce A. Chabner wrote in The Oncologist, a journal he edits:
Dr. Bertino began his remarkable career in research in Seattle in the late 1950s, where he worked with one of the great biochemists of that generation, Frank Huenneikens.
[Bertino] discovered that methotrexate exposure led to a rapid increase in the intracellular level of its target, probably an effect on dihydrofolate reductase (DHFR) transcription, and later, with Bob Schimke at Stanford, he reported the quite remarkable observation of gene amplification of DHFR, opening a whole new era in drug resistance research and unveiling an unexpected aspect of the plasticity of the tumor genome.
Many other important observations followed, both in the laboratory and in the clinic, including the evolution of high-dose methotrexate therapy and other aspects of methotrexate pharmacology.
Largely as a result of his work, this drug has become the stalking horse for understanding how cancer drugs work and why they fail.
Chabner is a professor of medicine at Harvard Medical School and director of clinical research at MGH Cancer Center, Massachusetts General Hospital. His appreciation of Bertino appears here.
In a 2013 interview with a publication at Rutgers Cancer Institute of New Jersey, where he spent nearly 20 years, Bertino said his insight into methotrexate came when he was on sabbatical from Stanford from 1976 to 1977, working with colleagues 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,” Bertino said. “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.”
Working with colleagues and trainees, Bertino is credited with defining many foundational principles of cancer biology, including mechanisms of chemotherapy cytotoxicity and principles of drug resistance. Colleagues say that Bertino’s early work, done a half a century ago, led to development of combination chemotherapy that cured patients with non-Hodgkin’s lymphoma and acute leukemias.
Bertino’s work on folate metabolism led to the concept of leucovorin rescue for high-dose methotrexate in patients with osteosarcoma and acute lymphoblastic leukemia as well as the development of an alkylating-agent free regimen (sequential methotrexate fluorouracil) adopted by Bernard Fisher and the National Surgical Adjuvant Breast and Bowel Program for use in the adjuvant treatment for pre-menopausal women with breast cancer, colleagues say.
“I was introduced to Joe over 40 years ago, as a second-year medical student at Yale, where Joe served as my pharmacology course discussion leader,” said Bruce G. Haffty, associate vice chancellor for cancer programs and chair of the Department of Radiation Oncology at Rutgers Robert Wood Johnson and New Jersey Medical Schools, and Rutgers Cancer Institute. “Like countless other medical students, doctoral candidates, residents, fellows and junior attendings, we were inspired by Joe’s passion, dedication and commitment to cancer research and moving the field of oncology forward.”
Photo credit: ©2008 AACR/Todd Buchanan
In 1973, Bertino was put in charge of the application for Yale’s designation as a comprehensive cancer center, with the promise that he would become the center director upon designation, which occurred a year later, oncologist David S. Fischer wrote in a history of the cancer center.
“Just as all this was coming together, Bertino was offered a Career Research Professorship by the American Cancer Society,” Fischer wrote. “It was too good to turn down. It would allow Bertino to devote more time to his basic research in his pharmacology laboratory and to his clinical research interests as chief of medical oncology, but it would not permit him to spend time as an administrator, especially not one so demanding as Director of a Cancer Center. He resigned effective June 30, 1975.”
Altogether, Bertino spent 25 years at Yale, followed by 16 years at Memorial Sloan-Kettering Cancer Center, where he headed the new Chemotherapy Research Program and codirector of the Developmental Therapy & Clinical Investigation Program.
“I was his first faculty recruit [at MSKCC], and have remained a collaborator and friend throughout my career,” said Kathleen W. Scotto, now vice chancellor for research and research training, Rutgers Biomedical and Health Sciences, vice dean at the School of Graduate Studies, director of the NJACTS (CTSA) Fellows Program and professor of pharmacology, Robert Wood Johnson Medical School at Rutgers University.
“Joe created a ‘translational’ research environment within the department long before it was in vogue, bringing together clinical oncologists and basic scientists to tackle key problems in the diagnosis and treatment of cancer,” Scotto said. “While a renowned researcher and compassionate and beloved clinician, Joe often said that his greatest accomplishment was training the next generation of cancer researchers; those of us privileged to be mentored by Joe are forever linked, to him and to each other by this experience.”
In 2002, William N. Hait recruited Bertino to Rutgers Cancer Institute of New Jersey. Hait, the founding director of the Rutgers cancer center, is now the global head for external innovation at Johnson & Johnson.
Photo credit: ©2008 AACR/Todd Buchanan
“I was fortunate to be a fellow in Joe’s Division of Medical Oncology at Yale, where he was a role model for us physician-scientist wannabes,” Hait said. “He led by example, a kind compassionate physician, outstanding teacher and a brilliant investigator. His broad respect in the oncology community was exemplified by his election to the presidencies of both AACR and ASCO as well as being appointed the first editor-in-chief of ASCO’s Journal of Clinical Oncology.”
Bertino was a former president of the American Society of Clinical Oncology (in 1975) and the American Association for Cancer Research (in 1995). In 1992, he received ASCO’s David A. Karnofsky Memorial Award, and in 2018, the AACR Lifetime Achievement Award.
At the time of his death, Bertino was the University Professor of Medicine and Pharmacology at Rutgers Robert Wood Johnson Medical School. He was senior advisor to the director of Rutgers Cancer Institute of New Jersey in New Brunswick and director of the Pharmacokinetics and Pharmacodynamics Shared Resource there.
Bertino was also the cancer center’s former chief scientific officer and a former interim director.
“My personal experience with Joe is highlighted by great respect for years of his scientific guidance, professional mentorship and friendship at Rutgers Cancer Institute of New Jersey,” said Roger Strair, chief, Blood Disorders, Rutgers Cancer Institute and professor of medicine at Rutgers Robert Wood Johnson Medical School.
For me, he was an amazing role model on how to be a physician-scientist and gentleman-scholar, a true rarity these days in academic medicine.
Edward Chu
“I first familiarized myself with his scientific expertise and creativity when I was a graduate student in the late 1970’s, admiring greatly his cell biology work on methotrexate resistance and gene amplification,” Strair said. “When he was much later recruited to Rutgers Cancer Institute of New Jersey, we began interacting regularly at weekly clinical and research meetings, as well as at the American Society of Hematology annual meeting, Lymphoma Research Foundation meetings and several social outings including ventures to sporting events at Yankee Stadium or Madison Square Garden.
“Those interactions will forever be remembered for his intelligence, collegiality, humor and friendship.”
To Edward Chu, whose parents worked at the Department of Pharmacology at Yale Cancer Center, Bertino was Uncle Joe.
“I was privileged to have known Joe since I was a child growing up in New Haven, and then to have developed a relationship with him as a colleague, collaborator, friend, and mentee over these many years,” Chu, director of the Albert Einstein Cancer Center and vice-president of Cancer Medicine at Montefiore Medicine, said to The Cancer Letter.
“For me, he was an amazing role model on how to be a physician-scientist and gentleman-scholar, a true rarity these days in academic medicine,” Chu said.
“He was a true giant in the field of medical oncology and cancer research, and he instilled in all of his many mentees the importance of treating patients and colleagues with dignity and respect.”
In his 2008 tribute to Bertino, Chabner wrote:
I could not end this note of admiration for Dr. Bertino without recognizing his accomplishments as an athlete! A talented collegiate basketball player in the era of 6′2″ centers, Joe turned his attention to softball, tennis, and golf. His weekly tennis matches with Paul Marks at Memorial were legendary for their intensity and skill, and continued for many years, although no one but they know the final score.
Bertino’s wife Patricia died in 2011. He is survived by his four children: Fred, Amy, Tom and Paul and their families, which include several grandchildren and great-grandchildren. He is also survived by his brother Tom.
Arrangements are as follows:
Sunday, Oct. 17
Wake/viewing
2pm-4pm, and 6pm-8pm
W.S. Clancy Memorial Funeral Home
244 N Main St, Branford, CT 06405
Monday, Oct. 18
11am Mass at
St. Joseph’s Church
129 Edwards St, New Haven, CT 06511
Monday, Oct. 18
Reception/Celebration of Life
12 noon immediately following the Mass
New Haven Lawn Club at Yale
193 Whitney Ave, New Haven, CT 06511
Condolences can be sent to:
Bertino Family
135 Somerset St – Apt 705
New Brunswick, NJ 08901
