Treatments Found in Translational Science

Behind every cancer patient stands a long line of researchers they will never know, although their work and expertise remain critical to their outcomes.

Reflecting the complexities of the disease, cancer research is an ever-evolving field requiring constant infusions of innovation and funding. Starting this year, those resources at Yale Cancer Center will be augmented by its Translational Incubator, an initiative to further support and accelerate cooperation and collaboration among Yale experts.

“There’s basic science research that we want to get to patients, and we just have to create more connections to move it forward,” explained Barbara Burtness, MD, associate director for translational research at Yale Cancer Center and co-leader of the Developmental Therapeutics research program. “The purpose of the incubator [is to] take the culture of translation to all our scientists and all our clinical investigators.”

In the research world, “translation” means transforming basic scientific findings in a laboratory setting into potential treatments for disease. It routinely involves painstaking research to provide evidence of its viability as a treatment. Once that phase is complete, approval is sought to test the potential treatment with patients who volunteer for clinical trials.

Sometimes referred to as “bench to bedside” the translational process is closely regulated and typically takes years. Facilitating this process is the aim of the Translational Incubator.

“Our purpose is to create excitement among potential users…all the people who have not consistently been seeking out translational opportunities,” said Dr. Burtness, the Anthony N. Brady Professor of Medicine (medical oncology) at Yale School of Medicine.

It’s “how we can jump-start the next step. You have to get the right people into the room,” she said. “You have to figure out who should be talking to each other and then create [ways] they can do that.”

Like tech, business, or development incubators, the Translational Incubator is meant to provide evaluation, guidance, and assistance to investigators who believe that a finding in the laboratory is ready to be explored clinically or a clinical finding merits laboratory investigation.

The incubator will be “a touchpoint for people as they want to think about accessing shared resources and we’ll be keeping a curated list of translational funding opportunities,” Dr. Burtness said.

In addition, the incubator will direct investigators to the cancer center shared resources, which include services, technologies, and scientific consultations in a half dozen areas that include cancer biostatistics, pathology tissue services, genomic analysis, and molecular discovery. Each resource is led by a cancer center expert.

The incubator also will have its own resources, including a science writer as well as a research affairs professional, who will have office hours to meet with researchers. Pratima Chaurasia, PhD, is enthused about that new role. “I’ve dedicated my life to science,” said Chaurasia, a successful scientist who has just completed a new assay in the Yale Center for Genome Analysis. “I’m excited about helping with building [relationships]…about helping them to build a network and the right collaborators…so they can develop their scientific ideas and careers.”

The incubator’s steering committee, chaired by Dr. Burtness, will include five YCC associate directors—Translational, Clinical, and Basic Sciences, Shared Resources and Experimental Therapeutics—and the deputy director for Population Sciences. It will meet monthly to consider concepts from basic and clinical investigators and to prioritize the proposals, based in part on catchment area needs, alignment with the center’s strategic priorities, and potential impact. The steering committee will also meet bimonthly with the cancer center’s six research program leaders to promote collaboration and bring concepts to the Incubator.

“We’ll also keep track of publications and grant submissions,” so that the information can be shared and suggest areas for partnerships, Dr. Burtness said. “It could be like ‘Have you seen so-and-so’s amazing data? We are thinking about how cool this would be in your model.’ It’s trying to understand where the synergies might be.”

Those multi-disciplinary synergies, or “team science” collaborations, leverage the strengths and expertise of diverse professionals in different aspects of the same field and can be effective in tackling complex scientific and societal problems, says the National Cancer Institute. Team science is important to nurture as competition for research dollars intensifies, despite the enviable fact that the US government devotes more money to cancer research, about $7.3 billion in 2023, than any other single entity in the world.

The Translational Incubator’s precursor was the less formal Drug Candidate Review Group operated by the leaders of Developmental Therapeutics (Dr. Burtness and Karen Anderson, PhD, YSM professor of pharmacology and of molecular biophysics and biochemistry) over the last six to seven years. The review group provided a forum where colleagues could learn about “this large number of promising new compounds [with the aim of] connecting those people with others doing disease-specific research, disease-specific models and [who were] interested in taking these into the clinic,” Dr. Burtness said.

“The idea was how could we help these people who had incredible basic science stories find translational ways forward,” Dr. Burtness said of the review board. It met about a half dozen times a year, assembling different experts depending on the science being reviewed, but with a handful of core members who attended each session.

“We assembled a small group of translational investigators, animal modelers, pathologists interested in biomarker characterization, and early phase clinical trialists,” she explained. “It was very interactive, every slide got discussed” and ideas were kicked around.

Among the translational projects advanced by YCC and the Drug Candidate Review Group are pH low insertion peptides, combination FGFR and HDAC inhibitor therapy, and KDM5 inhibitors. Those research discoveries, combined with efforts to translate the work into viable treatments via Developmental Therapeutics, has yielded other outstanding Yale successes, including:

• The proteasome inhibitor molecule carfilzomib, now FDA-approved as standard of care for multiple myeloma

• Development of proteolysis-targeting chimeras (PROTACs) with applications envisioned for numerous cancers and the advancement of the PROTAC ARV-110 for treatment of metastatic castrate-resistant prostate cancer (mCRPC) in a clinical trial at Yale.

“With the launch of the Translational Incubator, we believe the process of moving concepts from the lab to the clinic will be more streamlined than ever before,” said Eric Winer, MD, the director of YCC.

Treatment-altering cancer research at Yale stretches back to the earliest chemotherapy, first introduced for patient use at Yale in the early 1940s, and remains robust today, now newly supported by the Translational Incubator.

Not every Yale researcher will be physically present at a patient’s bedside, but their work makes each step in their cancer treatment possible.