Speakers at the Vanderbilt-Ingram Cancer Center 25th Annual Scientific Retreat detailed the history of hereditary cancer discoveries and gave overviews about ongoing research.
But for one speaker, the history was deeply personal. Displaying family photographs, Damaris Olagundoye, MD, shared how breast cancer and ovarian cancer had affected generations of her family, including herself. A survivor of both breast and kidney cancer, Olagundoye said she didn’t learn until her diagnosis that a mutation in the BRCA2 gene ran through her maternal bloodline.
Reflecting upon her mother’s passing from ovarian cancer, she said, “Ovarian cancer wasn’t even on our radar. It came like a stealth bomber to eviscerate all her hopes and dreams of grandkids’ graduations.”
Now, the women in her family are getting tested for the mutation and undergoing intensive screening regimens or prophylactic surgeries. Olagundoye also delivered a message of appreciation.
“Human existence is paradoxically so frail and yet so powerful,” she said. “Oncologists, you help us hook into that power that turns visions into existence, struggles into triumphs, and dreams into reality by breathing new life into our dying hope — that hope that sees the invisible, feels the intangible, and believes the impossible.”
The other speakers included internationally renowned cancer researchers, notably Bert Vogelstein, MD, who has been named the most highly cited scientist in the world by the Institute for Scientific Information and is known for his groundbreaking work on the genetics of cancer. The co-director of the Ludwig Institute at Johns Hopkins and director of the Lustgarten Dedicated Laboratory for Pancreatic Cancer Research at the Sidney Kimmel Comprehensive Cancer Center, Vogelstein provided a historical timeline of his research that led in 2017 to the U.S. Food and Drug Administration’s (FDA) first approval for a cancer drug prescribed according to molecular phenotype instead of a specific organ site. That drug is the immunotherapy pembrolizumab.
The line of scientific inquiry was born from Vogelstein’s quest to understand Lynch Syndrome, an inherited disorder that puts people at increased risk for hereditary cancers. The story is one of persistence and patience.
Vogelstein noted that about 16 years passed between when his lab linked mismatch repair deficiency, also known as microsatellite instability, to hereditary colorectal cancer, and to when pembrolizumab was initially approved by the FDA for only melanoma and lung cancer. Researchers at that time did not know why other cancer types didn’t respond to pembrolizumab.
He asked Suzanne Topalian, MD, the leader of the team of pembrolizumab researchers, whether patients with any other type of cancer had responded to the treatment. She answered that one woman with colorectal cancer did have a durable response.
“At that moment, the people in our lab, we all had a collective ‘eureka moment,’” Vogelstein said. “We immediately understood what was going on. We all immediately recognized what this was telling us. It was saying it’s got a lot of mutations . . . And secondly, we realized in the same kind of ‘eureka moment’ that the patients who would respond best would be those who had mismatch repair.”
After next learning this patient’s colorectal tumor tested positive for mismatch repair deficiency, Vogelstein approached both the academic journal that had published the study that led to pembrolizumab’s initial approval as well as the drug marker about a follow-up clinical trial that would test the drug’s effectiveness for cancers of all types with microsatellite instability. Both turned him down, so he was able to convince Johns Hopkins to sponsor the trial.
“Patients with mismatch repair deficiency had a rather remarkable response,” he said. “I think one of the unique aspects of this whole story is that it was the first time a drug had been approved by the FDA for use in patients independent of the cancer type . . . This really kind of epitomized the idea of personalized or precision medicine.”
The annual scientific retreat is also a celebration of the achievements of graduate students and postdoctoral scholars committed to cancer research. Mirazul Islam, MS, was named VICC Graduate Student of the Year. His research focuses on developing new technologies in the field of single-cell multimodal genomics. Jackie Bader, PhD, was named VICC Postdoctoral Scholar of the Year. Her research focuses on the role of macrophages in colorectal cancer and the effects of obesity.
The scientific poster session and competition is also a highlight of the event. Winners receive monetary prizes. Amanda Hesterberg won the top Overall Exceptional Poster prize and $500. First, second and third prize winners in three categories won $300, $200 and $100, respectively.
Basic Science: first, Hillary Layden, PhD; second, Emily Arner, PhD; third, Abigail Rich.
Population Science: (two top winners) first, Thuraya Al-Sayegh, MD; first, Alvina Liang; second, Tina Cha. (No third-place price was awarded.)
Translational Science: (two top winners) first, Destiny Ball; first, Taylor Sheehy; second, Abigail Fabiano; third, Sarah Glass.
