The Division of Hematology/Oncology is actively advancing the understanding, diagnosis, and treatment of cancer and hematological disorders through nationally-recognized basic, translational, clinical, and population-based research programs. The Division has enjoyed a long history of outstanding research support, with $26 million in total research funding in FY 2019 and $11.7 million in peer-reviewed direct funding. The UPMC Hillman Cancer Center serves as the hub for the Hematology/Oncology scientific and clinical research activities in cancer. UPMC Hillman is Western Pennsylvania’s only National Cancer Institute (NCI)-designated Comprehensive Cancer Center and is ranked 12th in NCI funding.
Through our clinical research programs, our faculty are defining lifesaving approaches and accelerating the transformation of breakthroughs in their laboratories into clinical application for patients within the region and beyond. Clinical faculty are actively enrolling patients into clinical trials that investigate novel agents and combination regimens. In 2018-19, Division faculty enrolled 1,231 patients into various therapeutic, non-therapeutic, and compassionate-use clinical trials.
Within the Division, several members are internationally recognized for their leadership and expertise in various sold tumors. With the patient at the center of its mission, Division faculty strive to improve their understanding of the biological basis of cancer to develop new approaches for the prevention of cancer and to refine and redefine the ways in which patients are diagnosed and treated.
Benign Hematology Research
The Division includes a Section of Benign Hematology with more than 10 physician-scientists and research investigators, and is of the largest benign hematology programs in the U.S. Areas of excellence include hemophilia and bleeding disorders, and sickle cell disease The section oversees more than 20 clinical studies, primarily in sickle cell disease, but with a growing number of trials in other areas of benign hematology, such as acquired platelet disorders and autoimmune hemolytic anemias.
Fall 2022 Research Highlights
- A Phase 1 Dose Escalation Study of the Pyruvate Kinase Activator Mitapivat (AG-348) in Sickle Cell Disease. In this Phase 1 single-center, open-label study of the novel red-cell pyruvate kinase (PKR) activator mitapivat (AG-348) for the treatment of sickle cell disease (SCD), led by Dr. Julia Xu and published in the journal Blood, the team evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses of mitapivat in 17 adults with HbSS disease. The study found that mivapivat was overall safe and well tolerated, with no drug discontinuations for treatment-related adverse events. Of the 16 subjects completing at least 3 ascending dose levels of mitapivat, 9/16 (56.3%) subjects achieved a hemoglobin response of ≥ 1 g/dL increase compared to baseline. Mean reductions in hemolytic markers and dose-dependent decreases in mean 2,3-DPG and increases in mean ATP levels were observed, in line with mitapivat’s mechanism of action. This study provides proof of concept that mitapivat has disease-modifying potential in patients with SCD. (Xu JZ, …, Thein SL. Blood. 2022 May 16:blood.2022015403. https://pubmed.ncbi.nlm.nih.gov/35576529/)
- Hematopoietic stem cell regeneration through paracrine regulation of the Wnt5a/Prox1 signaling axis. A recent publication in the Journal of Clinical Investigation from Dr Wei Du’s lab investigates the crosstalk between the bone marrow (BM) niche and hematopoietic stem cells (HSCs) in HSC regeneration. Dr. Du’s team identified a paracrine Wnt5a/Prox1 Signaling axis as a regulator of HSCs regeneration under conditions of injury and aging, therefore suggesting a potential target for improving HSC function under stressed conditions. (Lin Q, Wu L, Chatla S, Chowdhury FA, Atale N, Joseph J, Du W. J Clin Invest. 2022 Jun 15;132(12):e155914. PMC9197516 https://pubmed.ncbi.nlm.nih.gov/35703178/)
- Differential responses to immune checkpoint inhibitor dictated by pre-existing differential immune profiles in squamous cell carcinomas caused by same initial oncogenic drivers. New Research published in the Journal of Experimental & Clinical Cancer Research from Dr. Jing Hong Wang‘s lab has uncovered tumor-intrinsic differences between two SCC tumor lines (TAb2 and TCh3), both of which harbor TP53 deletion and PIK3CA hyperactivation, and their differential response to anti-PD-L1 therapy. The study demonstrates that stratifying cancers according to their genetic alterations alone is not sufficient in determining immune checkpoint inhibitor (ICI) efficacy. In addition, the findings suggest that evaluating HNSCC tumor-intrinsic cues along with immune profiles in the TME may help better predict ICI responses in individual hosts. The experimental models used may provide a platform for pinpointing tumor-intrinsic differences underlying an immunosuppressive TME in HNSCCs and for testing combined immunotherapies targeting either tumor-specific or TAM-specific players to improve ICI efficacy. These findings may be translatable to individual HNSCC patients with unique TMEs (e.g., higher expression of CSF1/VEGF-C), and determine if these multi-factorial profiles will help identify patients who may benefit from ICI therapy or other personalized therapies. (Chen SMY, …. , Wang JH. J Exp Clin Cancer Res. 2022 Apr 2;41(1):123. PMC8976353. https://pubmed.ncbi.nlm.nih.gov/35366939/)
- Dr. Jing Hong Wang / Dr. Robert Ferris (MPI):
“Identifying cellular and molecular signatures from distinct T cell receptor clonotypes associated with favorable immune checkpoint inhibitor responses in HNSCCs”
- Dr. Donna Posluzny (PI):
“Dyadic Intervention to Improve Patient-Family Caregiver Team-Based Management of the Medical Regimen after Allogeneic Hematopoietic Cell Transplantation”
- Dr. Taofeek Owonikoko (PI):
“Targeting PLK1 for therapy of small cell lung cancer”
- Dr. Riyue Bao / Dr. Jason Luke (MPI):
“Immune exclusion in cancer immunotherapy”
- Dr. Yana Najjar / Dr. Greg Delgoffe / Dr. Amanda Poholek (MPI):
“Dissecting the role of hypoxia in T cell differentiation in cancer”
- Dr. Dawar Diwakar will present the following talks at the upcoming SITC meeting in Boston
- “Neoadjuvant nivo/vidu in high-risk resectable melanoma.”
- “Phase I study of TLR7/8 agonist TC TLR 7/8 in advanced solid tumors.”
Division of Hematology/Oncology
UPMC Cancer Pavilion
5150 Centre Avenue, 5th floor
Pittsburgh, PA 15232
412-648-6575 | Email Us
UPMC Hillman Cancer Center
5115 Centre Avenue
Pittsburgh, PA 15232