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Dr. David Lyden, the Stavros S. Niarchos Professor in Pediatric Cardiology and a professor of pediatrics at Weill Cornell Medicine, has been named the winner of the 2024 Paget-Ewing Award by the Metastasis Research Society.  

The Paget-Ewing Award is the highest honor bestowed by the society and recognizes a person’s scientific excellence and substantial contributions to the understanding and control of cancer metastasis. The award is named after Dr. Stephen Paget and Dr. James Ewing, pioneers in metastasis research in the late 19th and early 20th centuries, who proposed the two major theories to explain the organ selectivity of metastasis.

Dr. Lyden is being recognized for his work identifying the pre-metastatic niche, the cellular and molecular changes in a future organ site destined to become a site of metastatic disease, and his ongoing research targeting the pre-metastatic niche to prevent or better treat metastases. “We found that cancer, once it’s developed, releases factors that are key in setting up metastases,” said Dr. Lyden, who is also a professor of cell and developmental biology and a member of the Sandra and Edward Meyer Cancer Center and the Gale and Ira Drukier Institute for Children’s Health.

By interfering with the production or reception of these signals, which cause immune cells and other neighboring cells in the pre-metastatic niche to respond inappropriately and support metastases, cancer progression may be blocked. “Our long-term goal is to use this approach to prevent and treat metastases,” he said.

Dr. Lyden and his team discovered that the tumors are communicating with distant organ sites via exosomes–small, virus-sized, extracellular vesicles. These exosomes have a protein or “zip code” on their surface comprised of molecules known as integrins, he said. “They’re adhesion molecules, acting like glue. They dictate which organ these exosomes are going to go to.”

In addition, Dr. Lyden discovered another smaller particle, the exomere, which is less than 50 nanometers in diameter. These miniscule bodies affect normal organ metabolism and, indirectly, a patient’s immune cells. Combined with exosomes, they promote inflammation at future sites of metastasis and mediate the systemic effects of cancer such as organ failure, immune cell dysregulation and thrombosis.

Having all of this new information changes the path forward for cancer research, said Dr. Lyden, since, if investigators can identify which integrin is contained on the exosome, they can predict in which organ metastasis will develop and potentially preemptively treat it.

“This offers a huge prognostic advantage for the clinician who can then possibly predict whether their patient is going to get metastases and in which organs,” he said. “You may monitor that organ with better imaging technologies, and you also may treat those patients differently than the patients that are unlikely to metastasize.”

“David is a richly deserving recipient of the Paget-Ewing Award,” said Erik Sahai, president of the Metastasis Research Society (MRS). “His pioneering work on the pre-metastatic niche has profoundly influenced how we think about the process of metastasis, and our understanding of cancer as a systemic disease.” The MRS conference and ceremony for the award will take place at the Francis Crick Institute in London, England in June.

Dr. James Ewing was the first professor of pathology at Weill Cornell Medicine and a founder of the American Association for Cancer Research. His achievements included the discovery and characterization of Ewing’s Sarcoma, a form of bone cancer, and the recognition of radiation as cancer treatment. In his work, he noted that cancer cells are directed to the metastatic site by the flow of lymphatic and circulatory systems. For his part, Dr. Paget developed the “seed and soil” theory, which proposed that metastasis relied on the compatibility of the tumor cells or the “seeds,” and the host organ, the “soil.”

“We found that the exosomes from the tumor actually condition this ‘soil’ to prepare it for metastases,” Dr. Lyden said. “Thus, our research adds to Drs. Paget and Ewing’s work, and that’s exciting.”