Tomoo Iwakuma, MD, PhD
Director, Translational Oncology Research Laboratory; Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Professor of Cancer Biology, University of Kansas School of Medicine
Full BiographyJohn M. Perry, PhD
Associate Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Assistant Professor of Pediatrics, University of Kansas School of Medicine
Full Biography
Tomoo Iwakuma, MD, PhD, and John Perry, PhD, Hematology/Oncology/BMT, both received advisory board grants from the Masonic Cancer Alliance (MCA).
Dr. Iwakuma’s two-year, $250,000 grant is being used for his study, “Taxane sensitivity is a novel vulnerability imposed by overexpressed MDM2.”
MDM2 functions as an oncogene, a gene that has the potential to cause cancer, mainly by inducing degradation of the tumor suppressor p53 protein. MDM2 is overexpressed in approximately 30 percent of human sarcomas.
According to Dr. Iwakuma, recent reports in human clinical trials suggest that MDM2 inhibitors cause significant side effects, including bone marrow suppression and gastrointestinal toxicities with modest anti-tumor effects. This suggests how important it is to identify alternative strategies that target overexpressed MDM2.
Increasing evidence indicates p53-independent oncogenic functions of MDM2; however, no drug that inhibits the p53-independent cancer-promoting activity of MDM2 is clinically available.
As the group works to identify such drugs, they have already performed high throughput drug screening and identified taxanes as drugs that specifically kill MDM2-overexpressing p53-deficient (p53KO) osteosarcoma (OS) cells as compared to MDM2/p53-double knockout (DKO) OS cells. Taxanes are a group of drugs that specifically bind to tubulin and inhibits microtubule (MT) depolymerization, hence called as “MT-stabilizing chemotherapy agents”.
“Completion of this study will not only identify vulnerabilities imposed by overexpressed MDM2 (increased taxane sensitivity), but also reveal yet unappreciated MDM2 function and the novel targets, thereby having high impact on public health,” wrote Dr. Iwakuma. “There is the potential to lead to the discovery of a novel anti-cancer therapy that targets overexpressed MDM2.”
Michael Washburn, PhD, of the University of Kansas Medical Center will serve as a co-investigator.
Dr. Perry’s two-year, $249,995 grant is for his study, “Investigation of stem-like T cells and their latent role in anticancer activity.”
The study will explore the possibility of using the rare, highly potent “stem-like T cells” as anti-cancer vaccines. According to Dr. Perry, these cells combine the cancer-fighting activity of mature T cells and the long-term staying-power and replicative ability of stem cells.
Dr. Perry and his team are using single-cell genomic and proteomic analysis to investigate immunological changes during development of hematopoietic stem cells (HSCs), leukemia stem cells (LSCs), and their offspring in response to low dose anthracycline treatment. Comparing minimal residual disease (MRD) patient samples, the team has found that different proportions of stem-like T cells persist in the bone marrow of leukemia patients. Their preliminary studies have revealed that low dose in contrast to high dose anthracyclines, anti-tumor antibiotics that work on the DNA inside cancer cells, create opposing effects on LSCs vs. HSCs and stem-like vs. differentiated T cells.
“In this study we will use cutting edge techniques to better understand and use these unique stem-like T cells and its ability to potently drive anti-cancer immunity,” said Dr. Perry. “Understanding them in detail will allow researchers and clinicians to harness stem-like T cells for better, more durable cures, especially against therapy resistant adult acute myeloid leukemia (AML).”
Mary Markiewicz, PhD, of the University of Kansas Medical Center will serve as a co-investigator.