Dr. Druker's research focuses on activated tyrosine kinases with an emphasis on signal transduction and cellular transformation and the application of this knowledge to cancer therapies. The BCR-ABL oncogene is his lab's primary model system because of its central role in the pathogenesis of a human disease, chronic myeloid leukemia (CML). Numerous tyrosine phosphorylated proteins have been identified in BCR-ABL transformed cells and projects are ongoing to define their necessity for BCR-ABL function. These studies include mutational, biochemical and genetic approaches. Imatinib (Gleevec), a specific inhibitor of the ABL protein tyrosine kinase, has been proven to be an effective therapeutic agent in CML. However, it is not capable of eliminating all leukemic cells. In laboratory correlate studies done alongside imatinib clinical trials, Dr. Druker's lab learned that ABL kinase domain mutations are the most common mechanism of resistance to imatinib. Using this information, his team has evaluated several novel ABL inhibitors that are now available to treat patients with Gleevec resistance. Lastly, Dr. Druker's lab is performing screens for other tyrosine kinases that may be pathogenic in other leukemias and has developed functional assays that allow rapid target identification.
- M.D., University of California San Diego 1981
- Barnes Hospital, Washington University, St. Louis
- Medical oncology - Dana-Farber Cancer Institute, Harvard Medical School, Boston
- American Board of Internal Medicine, 1984
Memberships and associations
- Institute of Medicine: National Academy of Sciences
- American Association of Physicians
- National Academy of Sciences
- American Society for Clinical Investigation
- American Society of Hematology
- American Society of Clinical Oncology
- American Association for Cancer Research
- American Association for the Advancement of Science
- American Society for Microbiology
- Children’s Oncology Group
- The American Society for Cell Biology
- "Molecularly targeted drug combinations demonstrate selective effectiveness for myeloid- and lymphoid-derived hematologic malignancies." Proceedings of the National Academy of Sciences of the United States of America In: , Vol. 114, No. 36, 05.09.2017, p. E7554-E7563.
- "Stability of patient-specific features of altered DNA replication timing in xenografts of primary human acute lymphoblastic leukemia." Experimental Hematology In: , Vol. 51, 01.07.2017, p. 71-82.e3.
- "Understanding cancer from the stem cells up." Nature Medicine In: , Vol. 23, No. 6, 06.06.2017, p. 656-657.
- "Identification of Interleukin-1 by Functional Screening as a Key Mediator of Cellular Expansion and Disease Progression in Acute Myeloid Leukemia." Cell Reports In: , Vol. 18, No. 13, 28.03.2017, p. 3204-3218.
- "Long-term outcomes of imatinib treatment for chronic myeloid leukemia." New England Journal of Medicine In: , Vol. 376, No. 10, 09.03.2017, p. 917-927.
- "Concurrent STAT3, DNMT3A, and TET2 mutations in T-LGL leukemia with molecularly distinct clonal hematopoiesis of indeterminate potential." American Journal of Hematology In: , Vol. 92, No. 1, 01.01.2017, p. E6-E8.
- "Analysis of acquired mutations in transgenes arising in Ba/F3 transformation assays : Findings and recommendations." Oncotarget In: , Vol. 8, No. 8, 2017, p. 12596-12606.
- "Functional validation of the oncogenic cooperativity and targeting potential of tuberous sclerosis mutation in medulloblastoma using a MYC-amplified model cell line." Pediatric Blood and Cancer In: , 2017.
- "Maternal, fetal, and neonatal imatinib levels with treatment of chronic myeloid leukemia in pregnancy." Obstetrics and Gynecology In: , Vol. 129, No. 5, 2017, p. 831-834.
- "Differentiation status of primary chronic myeloid leukemia cells affects sensitivity to BCR-ABL1 inhibitors." Oncotarget In: , Vol. 8, No. 14, 2017, p. 22606-22615.
- "Novel Method Enabling the Use of Cryopreserved Primary Acute Myeloid Leukemia Cells in Functional Drug Screens." Journal of Pediatric Hematology/Oncology In: , Vol. 39, No. 7, 2017, p. e359-e366.
- "PBA2, a novel inhibitor of imatinib-resistant BCR-ABL T315I mutation in chronic myeloid leukemia." Cancer Letters In: , Vol. 383, No. 2, 28.12.2016, p. 220-229.
- "FGF2 from marrow microenvironment promotes resistance to FLT3 inhibitors in acute myeloid leukemia." Cancer Research In: , Vol. 76, No. 22, 15.11.2016, p. 6471-6482.
- "Discovery and functional characterization of a germline, CSF2RB-activating mutation in leukemia." Leukemia In: , Vol. 30, No. 9, 01.09.2016, p. 1950-1953.
- "Clonal hematopoiesis as determined by the HUMARA assay is a marker for acquired mutations in epigenetic regulators in older women." Experimental Hematology In: , Vol. 44, No. 9, 01.09.2016, p. 857-865.e5.
- "Targeting BCL-2 and ABL/LYN in Philadelphia chromosome-positive acute lymphoblastic leukemia." Science Translational Medicine In: , Vol. 8, No. 354, 354ra114, 31.08.2016.
- "Ultrasensitive proteomic quantitation of cellular signaling by digitized nanoparticle-protein counting." Scientific Reports In: , Vol. 6, 28163, 20.06.2016.
- "A novel crizotinib-resistant solvent-front mutation responsive to cabozantinib therapy in a patient with ROS1-rearranged lung cancer." Clinical Cancer Research In: , Vol. 22, No. 10, 15.05.2016, p. 2351-2358.
- "Mutant calreticulin-expressing cells induce monocyte hyperreactivity through a paracrine mechanism." American Journal of Hematology In: , Vol. 91, No. 2, 01.02.2016, p. 211-219.
- "JAK2 results in cytokine hypersensitivity without causing an overt myeloproliferative disorder in a mouse transduction-transplantation model." Experimental Hematology In: , Vol. 44, No. 1, 01.01.2016, p. 24-29.e1.
- "Identification and characterization of tyrosine kinase nonreceptor 2 mutations in leukemia through integration of kinase inhibitor screening and genomic analysis." Cancer Research In: , Vol. 76, No. 1, 01.01.2016, p. 127-138.
- "IRS2 silencing increases apoptosis and potentiates the effects of ruxolitinib in JAK2-positive myeloproliferative neoplasms." Oncotarget In: , Vol. 7, No. 6, 2016, p. 6948-6959.
- "Age-related mutations and chronic myelomonocytic leukemia." Leukemia In: , 09.12.2015.
- "Cardio-oncology : How new targeted cancer therapies and precision medicine can inform cardiovascular discovery." Circulation In: , Vol. 132, No. 23, 08.12.2015, p. 2248-2258.
- "Extreme mutational selectivity of axitinib limits its potential use as a targeted therapeutic for BCR-ABL1-positive leukemia." Leukemia In: , 19.11.2015.
- "Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors." Proceedings of the National Academy of Sciences of the United States of America In: , Vol. 112, No. 39, 29.09.2015, p. E5381-E5390.
- "Functional RNAi screen targeting cytokine and growth factor receptors reveals oncorequisite role for interleukin-2 gamma receptor in JAK3-mutation-positive leukemia." Oncogene In: , Vol. 34, No. 23, 04.06.2015, p. 2991-2999.
- "Therapeutically targetable ALK mutations in leukemia." Cancer Research In: , Vol. 75, No. 11, 01.06.2015, p. 2146-2150.
- "YM155 potently kills acute lymphoblastic leukemia cells through activation of the DNA damage pathway." Journal of Hematology and Oncology In: , Vol. 8, No. 1, 39, 22.04.2015.
- "Self-Enforcing Feedback Activation between BCL6 and Pre-B Cell Receptor Signaling Defines a Distinct Subtype of Acute Lymphoblastic Leukemia." Cancer Cell In: , Vol. 27, No. 3, 09.03.2015, p. 409-425.