The Hematologic Malignancies research program focuses on advancing our understanding of molecular pathogenesis and treatment of leukemias and lymphomas. Examination of the differences between neoplastic cells and their normal counterparts has provided insight into the molecular and biochemical features that define the malignant phenotype. In addition, research on somatic mutations associated with tumors has provided a blueprint of the molecular features that contribute to disease development or progression.
Together with research on biochemical factors that govern cell-cycle progression, cellular differentiation, response to injury, and programmed cell death, there is greater appreciation of molecular pathways that could be targeted for development of novel anti-neoplastic drugs. Such agents should have a higher therapeutic index than standard chemotherapy.
Five themes in basic, translational, and clinical research govern this program: (1) lymphocytic leukemias and lymphomas; (2) myeloid leukemias; (3) hematopoietic stem cell transplantation; (4) pediatric leukemias, and; (5) leukemia stem cells.
A main goal of members is to implement a bench-to-bedside and bedside-to-bench approach to improve the therapeutic index of anti-leukemia/lymphoma therapy, and key strategies include:
- Identify mutations and/or aberrant signaling pathways in leukemias and related diseases that contribute proliferative/survival signals, impair differentiation, and/or confer properties of self-renewal to leukemic/lymphoma cells and/or stem cells.
- Use insights to generate accurate cell culture and animal models of leukemia/lymphoma, to improve our understanding of the pathogenesis of disease, and validate mutant genes as therapeutic targets.
- Develop and test novel therapeutic strategies in preclinical models.
- Test promising new approaches in Phase l/ll clinical trials.
- Conduct such clinical trials with pharmacokinetic and correlative-science studies on primary leukemia/lymphoma cells that examine whether the targeted molecular pathway(s) is being hit by therapy.
- Develop and validate surrogate endpoints for activity of novel therapeutic strategies for patients with leukemias and/or lymphomas that can be used in later-stage clinical trials.