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Researchers are using patient-derived tumor organoids to match patients with optimal treatments - When most people think of precision cancer medicine, they think of genomics, with researchers trying to decipher complex gene interactions for the clinical benefit of patients. But according to Dr. Christopher Kemp, a cancer biologist at the Fred Hutchinson Cancer Research Center, that is a narrow view: “[Genomics] is important, but it’s not the whole puzzle by any stretch.”

“Cancer cells that are cultured for extended periods of time can undergo a variety of changes and may not be representative of the tumor cells that are actually in a mouse or human,” says study first author Patrick Bhola, PhD, of Dana-Farber. “The challenge has been to create a drug-screening technique that shrinks the gap between tumor cells in the body and the cells we do the screening on. The technique we’ve developed helps to accomplish that.” Read Dana Farber’s press release about HT-DBP technology for more information.

Anthony Letai, PhD gives an overview of how BH3 profiling can be used to predict response to therapy. “There is an enormous amount of actionable information that can be obtained from taking the actual cancer cell you’re interested in and subjecting it to a relevant perturbation, that is, exposing it to the actual drugs,” he said. “We nearly completely overlook this in today’s precision medicine approaches, and I think there is enormous unrealized potential in this general approach.”

Because each patient’s cancer is unique, novel approaches are needed to translate clinical and genomic diagnostics to actionable information. While the concept of directly studying a given patient’s tumor cells using functional assays is simple and appealing, the execution is not. Major challenges include technical, analytical, and regulatory, as well as inherent skepticism concerning the use of personalized models for functional testing. Benefits include the ability to functionally interrogate an actual patient’s cancer in unprecedented detail using high throughput assays. This session will present strategies to overcome major challenges and will discuss different applications of functional testing including target identification, preclinical drug and companion diagnostic development, and identification of potentially effective drugs for cancer patients in real time. Attendees will gain an appreciation of how functional testing of patient derived tumor cells can reveal novel insights into cancer biology and accelerate the goals of precision medicine.

Last month, the Banbury Center held its “CSHL Technology and Education Council: Challenges and Promise in Precision Medicine” meeting (February 18-20). During this time, I was able to meet with Christopher Kemp, Ph.D., and learn about the oncology research he performs and how he’s hoping to make a difference through it. Dr. Kemp, a Full Member at the Fred Hutchinson Cancer Research Center in Seattle, WA, received his doctorate in oncology from the University of Wisconsin–Madison.

Acute myeloid leukemia (AML) results from the enhanced proliferation and impaired differentiation of hematopoietic stem and progenitor cells. Using an ex vivo functional screening assay, we identified that the combination of the BTK inhibitor ibrutinib and BCL2 inhibitor venetoclax (IBR + VEN), currently in clinical trials for chronic lymphocytic leukemia (CLL), demonstrated enhanced efficacy on primary AML patient specimens, AML cell lines, and in a mouse xenograft model of AML.

Most patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) do not benefit from current re-induction or approved targeted therapies. In the absence of targetable genetic mutations, there is minimal guidance on optimal treatment selection particularly in the R/R setting highlighting an unmet need for clinically useful functional biomarkers. Blood and bone marrow samples from patients treated on two clinical trials were used to test the combination of lenalidomide (LEN) and MEC (mitoxantrone, etoposide, and cytarabine) chemotherapy in R/R AML patients.

Jeffrey Tyner, Ph.D., has received an Emerging Leader Award from @TheMarkFdn for Cancer Research. The award will support his research seeking combinations of anticancer agents able to stop #AML by targeting unique vulnerabilities among patients.

Congratulations to Sara Cherry on her well-deserved Penn Medicine Stanley N. Cohen Biomedical Research Award! In recognition of an outstanding body of work in Biomedical Research!

A technique involving BH3 profiling is emerging as a promising drug discovery tool for assessing whether a tumor is primed for cell death and would respond to anticancer therapy, according to a presentation at the 2019 Association for Molecular Pathology Annual Meeting.