Silvia Formenti, Massimo Loda elected to National Academy of Medicine

Dr. Silvia Formenti, chair of the Department of Radiation Oncology and the Sandra and Edward Meyer Professor of Cancer Research at Weill Cornell Medicine, and Dr. Massimo Loda, chair of the Department of Pathology and Laboratory Medicine and the David D. Thompson Professor at Weill Cornell Medicine, have been elected to the National Academy of Medicine.

One of the most prestigious honors in health and medicine, the academy recognizes individuals who have demonstrated outstanding professional achievement and made major contributions to advancing the medical sciences, health care and public health.

"I'm very grateful, because it's one of the highest recognitions a physician can ever receive," said Formenti, also radiation oncologist-in-chief at NewYork-Presbyterian/Weill Cornell Medical Center. "But I don't feel any significant achievement is ever the result of a single person - it's always a team. Throughout my career in medicine, I have had original ideas but, most importantly, I was lucky to be able to inspire and lead many outstanding colleagues and trainees."

"Election to the National Academy of Medicine is extremely prestigious, and I'm very thankful," said Loda, also pathologist-in-chief at NewYork-Presbyterian/Weill Cornell Medical Center. "It is an honor and recognition that goes beyond the institution or people - it's more of a global recognition of one's accomplishments."

A novel approach: radiation, immunotherapy

A recognized leader in radiation oncology and breast cancer research, Formenti's innovative work has transformed the paradigm in radiation biology, identifying the important inflammatory and immunological effects triggered by ionizing radiation. She led the team that first demonstrated, preclinically, the effectiveness of combining focal radiotherapy with immunotherapy to control cancer cell growth in solid tumors. When combined with immune checkpoint inhibitor drugs, targeted radiotherapy can harness patients' immune systems to attack their tumor, resulting in a form of personalized immunotherapy. Formenti has translated these discoveries into clinical trials in metastatic solid tumors such as breast and lung cancer, as well as in brain metastases.

"In 2004, we were the first to publish a paper connecting the systemic effects of radiation on the immune system," she said. "Now there are thousands of protocols investigating how to best combine radiation therapy with immunotherapy to develop more effective treatments."

Board-certified in medical oncology, radiology and radiation oncology, Formenti earned her medical degree from the University of Milan and spent her early career in Italy and at University of Southern California (USC), where she worked in a cancer immunology laboratory. She believes her years of interdisciplinary education "served me a great deal to look at things from different angles and appreciate the relevance of the immune system in cancer," she said.

But, intrigued by the focal effectiveness of radiotherapy that results in local tumor control, since her first R01 at USC, she hypothesized a more systemic effect, and concentrated her research in radiation oncology to elucidate it. After 15 years at NYU Langone's Perlmutter Cancer Center, where she was professor and chairman of radiation oncology, Formenti came to Weill Cornell Medicine in 2015.

"I'm happy I did," said Formenti, who is also associate director for translational medicine at the Sandra and Edward Meyer Cancer Center and a member of the Englander Institute for Precision Medicine at Weill Cornell Medicine. "Weill Cornell gave me the opportunity to successfully recruit and build a very strong laboratory science program as a platform for translation to the clinic. And it keeps growing."

Formenti's research has led to more than 320 published manuscripts in prestigious journals, and since joining Weill Cornell Medicine she has been leading 18 investigator-initiated clinical trials. A fellow of the American College of Radiology, American Association for Cancer Research and ASTRO, Formenti has been awarded numerous federal and foundation grants, and including the Chemotherapy Foundation's Ezra Greenspan Award and the American Society for Radiation Oncology (ASTRO) Gold Medal Award, the highest recognition in the field of radiation oncology.

Her next "top goal" is to shepherd to completion a five-year, international effort to investigate the effects of the immune response in irradiated rectal cancer. Funded by an $8.1 million grant from the National Cancer Institute of the National Institutes of Health, the research - scheduled to end in 2027 - involves basic and clinical investigators from seven academic centers already engaged in the field of radiation and immunity research.

"At the same time, breast cancer remains my obsession, and there are still many paths to explore," Formenti said. "So the honor of the National Academy of Medicine cements my motivation to advance research, because I feel there is so much work left to be done."

Highlighting prostate cancer metabolism discoveries

Loda's renowned work in molecular pathology has illuminated the mechanisms by which prostate cancer hijacks cell metabolism to allow tumors to flourish. Unlike healthy cells, prostate tumors rely on fat, or lipids, for energy. Loda discovered that targeting this molecular pathway makes tumor cells vulnerable to cell death, leading to drugs that exploit this metabolic mechanism with few side effects. Loda has also identified prostate cancer biomarkers that can predict the effectiveness of specific therapies.

"The rewiring of metabolism in cancer to support its growth has always been a fascination of mine," he said. "We discovered that tumors are entirely dependent on certain fatty acids and have spent the last 25 years figuring out why. This has evolved to clinical trials using pharmacologic agents that target a critical metabolic enzyme in patients with prostate cancer. It's been an interesting path."

After completing his medical degree and residency in surgery at University of Milan, Loda completed a residency in anatomic pathology at Harvard Medical School as well as a fellowship at Tufts University focused on molecular pathology, a nascent discipline at the time. The field seemed an ideal fit since it allowed him to combine research and clinical care, focusing on pathogenetic mechanisms of disease.

"I'm interested in cancer pathogenesis and how this affects patients' therapeutic options and outcome, and pathology gives you the opportunity to bring the question back to the lab and investigate it," he said. "The combination was, for me, perfect."

Loda joined Weill Cornell Medicine in 2019 after serving as a professor of pathology at Harvard Medical School, chairing the Department of Oncologic Pathology at Dana-Farber Cancer Institute and serving as a co-leader of the Prostate Program at Dana-Farber/Harvard Cancer Center. He has received several honors, including the Donald S. Coffey Physician-Scientist Award from the Prostate Cancer Foundation, the Newton Abraham Professorship at the University of Oxford, Lincoln College and membership to the Association of American Physicians.

He has published more than 450 scholarly papers in leading journals. He has also served on several national advisory boards, leads the American Association for Cancer Research (AACR) Pathology Working Group and was a standing member of the Tumor Cell Biology study section at the National Cancer Institute.

Loda now wants to build on his vast body of work by expanding the early-phase clinical trials he's currently leading, to achieve co-targeting of oncogenic drivers and metabolic enzymes in prostate cancer patients. He hopes his research will lead to additional targeted prostate cancer treatments.

"In oncology, we've shifted in the last 20 or 30 years from a diagnosis of cancer that was simply organ-specific, treated with chemotherapy with relatively low specificity and undesired side-effects, to a biology-driven more granular and complex understanding of many more subtypes of cancer. Subtypes which may respond differently to different drugs or combination of therapeutic agents - including targeting lipid metabolism," he said. "There's been an evolution in this area and our work has been part of that."

Maureen Salamon is a freelance writer for Weill Cornell Medicine.

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