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Genomes and Genes | Neil P ShahSummaryAffiliation: University of California Country: USA Publications
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Publications
Bench to bedside: BRCA: from therapeutic target to therapeutic shieldNeil P Shah
Nat Med 14:495-6. 2008
Clinical resistance to the kinase inhibitor STI-571 in chronic myeloid leukemia by mutation of Tyr-253 in the Abl kinase domain P-loopSergei Roumiantsev
Center for Blood Research and Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115 5717, USA
Proc Natl Acad Sci U S A 99:10700-5. 2002..Because clinical resistance induced by the Y253F mutation might be overcome by dose escalation of STI-571, molecular genotyping of STI-571-resistant patients may provide information useful for rational therapeutic management...- Structure of the kinase domain of an imatinib-resistant Abl mutant in complex with the Aurora kinase inhibitor VX-680Matthew A Young
Departments of Molecular and Cell Biology and Chemistry, Howard Hughes Medical Institute, The University of California at Berkeley, Berkeley, CA 94720, USA
Cancer Res 66:1007-14. 2006.... - DasatinibNeil P Shah
Division of Hematology Oncology, UCSF School of Medicine, San Francisco, California 94143, USA
Drugs Today (Barc) 43:5-12. 2007..S. Food and Drug Administration for the treatment of imatinib-resistant and -intolerant chronic myeloid leukemia as well as its full approval for the treatment of therapy-resistant Ph+ acute lymphoblastic leukemia... - Progressive thoughts about progressive diseaseNeil P Shah
Division of Hematology/Oncology, University of California, San Francisco, San Francisco, California 94143, USA
Clin Cancer Res 13:5229-31. 2007 
Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemiaNeil P Shah
Division of Hematology Oncology, University of California, San Francisco School of Medicine, Box 1270, 505 Parnassus Ave, San Francisco, CA 94143, USA
J Clin Oncol 26:3204-12. 2008..Once-daily treatment resulted in less toxicity, suggesting that toxicity results from continuous inhibition of unintended targets. Here, a dose- and schedule-optimization study is reported...- Advanced CML: therapeutic options for patients in accelerated and blast phasesNeil P Shah
Division of Hematology Oncology, University of California, San Francisco, San Francisco, California, 94143, USA
J Natl Compr Canc Netw 6:S31-S36. 2008..However, BCR-ABL-independent pathways may also become more important, indicating that other therapeutic targets may also have a future role in managing patients with advanced CML... - Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intNeil P Shah
1Division of Hematology and Oncology, University of California, San Francisco School of Medicine, San Francisco, CA, USA
Haematologica 95:232-40. 2010..To better assess durability of response to and tolerability of dasatinib, data from a 2-year minimum follow-up for a dose-optimization study in chronic-phase chronic myeloid leukemia are reported here... - Transient potent BCR-ABL inhibition is sufficient to commit chronic myeloid leukemia cells irreversibly to apoptosisNeil P Shah
Division of Hematology Oncology, Department of Medicine, UCSF School of Medicine, San Francisco, CA 94143, USA
Cancer Cell 14:485-93. 2008..In CML patients receiving dasatinib once daily, response correlates with the magnitude of BCR-ABL kinase inhibition, thereby demonstrating the potential clinical utility of intermittent potent kinase inhibitor therapy... - Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potencyNeil P Shah
Division of Hematology Oncology, Department of Medicine, UCSF School of Medicine, San Francisco, California, USA
J Clin Invest 117:2562-9. 2007.... - Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosisNeil P Shah
Division of Hematology/Oncology, The David Geffen School of Medicine at University of California-Los Angeles (UCLA, CA, USA
Blood 108:286-91. 2006..Moreover, dasatinib may be of clinical utility in other disease settings driven by activating KIT mutations... - Dasatinib 140 mg once daily versus 70 mg twice daily in patients with Ph-positive acute lymphoblastic leukemia who failed imatinib: Results from a phase 3 studyMichael B Lilly
Chao Family Comprehensive Cancer Center, University of California, Irvine, Orange, USA
Am J Hematol 85:164-70. 2010..Compared with the 70 mg twice daily, dasatinib 140 mg once daily had similar overall efficacy and safety in patients with imatinib-resistant or intolerant Ph+ ALL. (clinicaltrials.gov identifier: NCT00123487)... - Equally potent inhibition of c-Src and Abl by compounds that recognize inactive kinase conformationsMarkus A Seeliger
Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkely, USA
Cancer Res 69:2384-92. 2009..Importantly, several of the DSA compounds block the growth of Ba/F3 cells harboring imatinib-resistant BCR-ABL mutants, including the Thr315Ile "gatekeeper" mutation, but do not suppress the growth of parental Ba/F3 cells... - Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemiaNeil P Shah
Department of Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
Cancer Cell 2:117-25. 2002..Multiple independent mutant clones were detected in a subset of relapsed cases. Our data support a clonal selection model of preexisting BCR-ABL mutations that confer imatinib resistance... - Clonal hematopoiesis in Philadelphia chromosome-negative bone marrow cells of chronic myeloid leukemia patients receiving dasatinibRonald L Paquette
Department of Medicine, UCLA, 42 121 CHS, Los Angeles, CA, USA
Leuk Res 34:708-13. 2010..After three years, no patient developed myelodysplastic syndrome or acute myeloid leukemia... - Overriding imatinib resistance with a novel ABL kinase inhibitorNeil P Shah
Division of Hematology and Oncology, Department of Medicine, The David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA
Science 305:399-401. 2004..These data illustrate how molecular insight into kinase inhibitor resistance can guide the design of second-generation targeted therapies... - Frequent EVI1 translocations in myeloid blast crisis CML that evolves through tyrosine kinase inhibitorsRonald L Paquette
UCLA Department of Medicine, Los Angeles, CA, USA
Cancer Genet 204:392-7. 2011..Inhibition of c-ABL kinase-mediated DNA double-strand repair by TKIs may predispose to EVI1 translocation in this setting... - BCL6-mediated repression of p53 is critical for leukemia stem cell survival in chronic myeloid leukemiaChristian Hurtz
Department of Laboratory Medicine, University of California San Francisco, CA 94143, USA
J Exp Med 208:2163-74. 2011..Clinical validation of this concept could limit the duration of TKI treatment in CML patients, which is currently life-long, and substantially decrease the risk of blast crisis transformation... - Tyrosine kinase inhibitor therapy for chronic myeloid leukemia: approach to patients with treatment-naive or refractory chronic-phase diseaseCatherine C Smith
Department of Hematology Oncology, University of California San Francisco, San Francisco, CA 94143 1270, USA
Hematology Am Soc Hematol Educ Program 2011:121-7. 2011..To this end, the latest seminal clinical trial results of approved and investigational BCR-ABL TKIs and some of the salient unique features of each of these agents are summarized herein... - Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistanceMichael R Burgess
Molecular Biology Institute, Howard Hughes Medical Institute, and Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
Proc Natl Acad Sci U S A 102:3395-400. 2005..The combination of imatinib plus BMS-354825 greatly reduced the recovery of drug-resistant clones. Our findings provide further rationale for considering kinase conformation in the design of kinase inhibitors against cancer targets... - Mechanisms of resistance to STI571 in Philadelphia chromosome-associated leukemiasNeil P Shah
Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
Oncogene 22:7389-95. 2003..Additionally, genomic amplification of the BCR-ABL gene can occasionally be detected. This review will highlight mechanisms of STI571 resistance in clinical samples as well as preclinical models... - Is it downhill from here? Eliminating leukemic stem cells and curing chronic myeloid leukemiaCatherine C Smith
Division of Hematology Oncology, Department of Medicine, University of California at San Francisco, San Francisco, California 94143, USA
Clin Cancer Res 17:6605-7. 2011..The rate of β decrease is consistent with declining leukemic stem cells and may predict which patients may safely discontinue therapy... - Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemiaCatherine C Smith
Division of Hematology Oncology, University of California, San Francisco, California 94143, USA
Nature 485:260-3. 2012..Our findings demonstrate that FLT3-ITD can represent a driver lesion and valid therapeutic target in human AML. AC220-resistant FLT3 kinase domain mutants represent high-value targets for future FLT3 inhibitor development efforts... - Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapyAndreas Hochhaus
III Medizinische Klinik, Medizinische Fakultat Mannheim, Universitat Heidelberg, Theodor Kutzer Ufer 1 3, 68167 Mannheim, Germany
Blood 109:2303-9. 2007..This trial was registered at www.clinicaltrials.gov as CA180013... - Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemiasMoshe Talpaz
Department of Leukemia, M.D. Anderson Cancer Center, Houston, USA
N Engl J Med 354:2531-41. 2006..CONCLUSIONS: Dasatinib induces hematologic and cytogenetic responses in patients with CML or Ph-positive ALL who cannot tolerate or are resistant to imatinib. (ClinicalTrials.gov number, NCT00064233 [ClinicalTrials.gov].)... - Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinasesTodd A Carter
Ambit, Inc, 4215 Sorrento Valley Boulevard, San Diego, CA 92121, USA
Proc Natl Acad Sci U S A 102:11011-6. 2005.... - Dynamics of chronic myeloid leukaemiaFranziska Michor
Program for Evolutionary Dynamics, Department of Organismic and Evolutionary Biology, Department of Mathematics, Harvard University, Cambridge, Massachusetts 02138, USA
Nature 435:1267-70. 2005..We calculate the probability of developing imatinib resistance mutations and estimate the time until detection of resistance. Our model provides the first quantitative insights into the in vivo kinetics of a human cancer... - Detection of BCR-ABL kinase mutations in CD34+ cells from chronic myelogenous leukemia patients in complete cytogenetic remission on imatinib mesylate treatmentSu Chu
Division of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA
Blood 105:2093-8. 2005..We conclude that BCR-ABL kinase mutations can be detected in CD34+ cells from CML patients in CCR on imatinib, may contribute to persistence of small populations of malignant progenitors, and could be a potential source of relapse...