Affiliation: Memorial Sloan-Kettering Cancer Center
- Finding and drugging the vulnerabilities of RAS-dependent cancersCharles L Sawyers
Howard Hughes Medical Institute, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
Cell 137:796-8. 2009..Two papers in this issue (Luo et al., 2009; Scholl et al., 2009) could change this landscape by uncovering kinase-specific vulnerabilities in tumors with RAS mutations...
- Something lost--something gained: the ASCI begins its second centuryCharles L Sawyers
Howard Hughes Medical Institute, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
J Clin Invest 118:1213-4. 2008..Their recollections provide a view of the changes that have occurred in academic medicine in general and for the physician-scientist in particular...
- Development of a second-generation antiandrogen for treatment of advanced prostate cancerChris Tran
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Science 324:787-90. 2009..These compounds thus appear to be promising candidates for treatment of advanced prostate cancer...
- Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen-receptor signaling axisHoward I Scher
Genitourinary Oncology Service, Department of Medicine, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
J Clin Oncol 23:8253-61. 2005..On the basis of this schema, we discuss strategies that are focused on the AR either directly or indirectly, as single agents or in combination, that are in clinical development...
- Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 studyHoward I Scher
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
Lancet 375:1437-46. 2010..Because growth of castration-resistant prostate cancer is dependent on continued androgen-receptor signalling, we assessed the antitumour activity and safety of MDV3100 in men with this disease...
- Targeting the androgen receptor pathway in prostate cancerYu Chen
Genitourinary Oncology Service, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Curr Opin Pharmacol 8:440-8. 2008..Many of these strategies are currently being tested in clinical trials in CRPC...
- Constitutively active androgen receptor splice variants expressed in castration-resistant prostate cancer require full-length androgen receptorPhilip A Watson
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Proc Natl Acad Sci U S A 107:16759-65. 2010....
- Targeted cancer therapyCharles Sawyers
Howard Hughes Medical Institute, David Geffen School of Medicine at UCLA, Jonsson Comprehensive Cancer Center, 10833 LeConte Avenue, Los Angeles, California 90095, USA
Nature 432:294-7. 2004..Recent progress in understanding the molecular changes that underlie cancer development offer the prospect of specifically targeting malfunctioning molecules and pathways to achieve more effective and rational cancer therapy...
- Mammalian target of rapamycin inhibition promotes response to epidermal growth factor receptor kinase inhibitors in PTEN-deficient and PTEN-intact glioblastoma cellsMaria Y Wang
Department of Pathology and Laboratory Medicine, Henry E Singleton Brain Tumor Program, Howard Hughes Medical Institute, David Geffen School of Medicine, University of California at Los Angeles, CA 90095 1732, USA
Cancer Res 66:7864-9. 2006..These studies provide strong rationale for combined mTOR/EGFR kinase inhibitor therapy in glioblastoma patients, particularly those with PTEN-deficient tumors...
- Opportunities and challenges in the development of kinase inhibitor therapy for cancerCharles L Sawyers
Howard Hughes Medical Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
Genes Dev 17:2998-3010. 2003
- ETV1 is a lineage survival factor that cooperates with KIT in gastrointestinal stromal tumoursPing Chi
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Nature 467:849-53. 2010..It also represents a novel mechanism of oncogenic transcription factor activation...
- Phosphorylation of the ATP-binding loop directs oncogenicity of drug-resistant BCR-ABL mutantsBrian J Skaggs
Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095, USA
Proc Natl Acad Sci U S A 103:19466-71. 2006..Therefore, mutations that confer clinical resistance to kinase inhibitors can substantially alter kinase function and confer novel biological properties that may impact disease progression...
- Cooperativity of TMPRSS2-ERG with PI3-kinase pathway activation in prostate oncogenesisJennifer C King
Memorial Sloan Kettering Cancer Center, New York, New York, USA
Nat Genet 41:524-6. 2009..TMPRSS2-ERG-positive human tumors are also enriched for PTEN loss, suggesting cooperation in prostate tumorigenesis...
- Integrative genomic profiling of human prostate cancerBarry S Taylor
Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
Cancer Cell 18:11-22. 2010..The genomic and clinical outcome data from these patients are now made available as a public resource...
- 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....
- The cancer biomarker problemCharles L Sawyers
Howard Hughes Medical Institute, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA
Nature 452:548-52. 2008..One of the main barriers to further progress is identifying the biological indicators, or biomarkers, of cancer that predict who will benefit from a particular targeted therapy...
- Will mTOR inhibitors make it as cancer drugs?Charles L Sawyers
Howard Hughes Medical Institute, Los Angeles, CA 90095, USA
Cancer Cell 4:343-8. 2003
- A novel pyridopyrimidine inhibitor of abl kinase is a picomolar inhibitor of Bcr-abl-driven K562 cells and is effective against STI571-resistant Bcr-abl mutantsDavid R Huron
Department of Medicine, Memorial Sloan-Kettering Cancer Center and Program in Pharmacology, New York, New York 10021, USA
Clin Cancer Res 9:1267-73. 2003..PD166326 is a prototype of a new generation of anti-Bcr-abl compounds with picomolar potency and substantial activity against STI571-resistant mutants...
- The nuclear factor-kappaB pathway controls the progression of prostate cancer to androgen-independent growthRen Jie Jin
Vanderbilt Prostate Cancer Center and Department of Urologic Surgery, Vanderbilt University Medical Center, A1329 MCN, 1161 21st Avenue South, Nashville, TN 37232 2765, USA
Cancer Res 68:6762-9. 2008..Thus, the NF-kappaB pathway may be a potential target for therapy against androgen-independent prostate cancer...
- Context-dependent hormone-refractory progression revealed through characterization of a novel murine prostate cancer cell linePhilip A Watson
Division of Hematology/Oncology, Department of Medicine, University of California at Los Angeles, 90095, USA
Cancer Res 65:11565-71. 2005....
- Molecular determinants of resistance to antiandrogen therapyCharlie D Chen
Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA
Nat Med 10:33-9. 2004..These findings provide insight toward the design of new antiandrogens...
- MicroPET imaging of prostate cancer in LNCAP-SR39TK-GFP mouse xenograftsHonghao Yang
Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine, 10833 LeConte Avenue, Los Angeles, CA 90095, USA
Prostate 55:39-47. 2003..Extension of this approach may allow repetitive imaging of tumor metastases...
- Whole-body skeletal imaging in mice utilizing microPET: optimization of reproducibility and applications in animal models of bone diseaseFrank Berger
The Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology University of California School of Medicine, 700 Westwood Blvd, Los Angeles, CA 90095, USA
Eur J Nucl Med Mol Imaging 29:1225-36. 2002..Morphological imaging with microCAT is useful to display correlative changes in anatomy. Detailed in vivo studies of the murine skeleton in various small animal models of bone diseases should now be possible...
- Growth inhibitory effects of the dual ErbB1/ErbB2 tyrosine kinase inhibitor PKI-166 on human prostate cancer xenograftsIngo K Mellinghoff
Department of Medicine, School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA
Cancer Res 62:5254-9. 2002..These results suggest that ErbB1/ErbB2 RTKs play an important role in the biology of androgen-independent prostate cancer and provide a rationale for clinical evaluation of inhibitors targeted to this pathway...
- Chromosomal aberrations in prostate cancer xenografts detected by comparative genomic hybridizationSari Laitinen
Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland
Genes Chromosomes Cancer 35:66-73. 2002..In conclusion, the identified genetic aberrations lay the groundwork for further detailed genetic analyses of these xenografts...
- TMEFF2 is an androgen-regulated gene exhibiting antiproliferative effects in prostate cancer cellsSigal Gery
Division of Hematology Oncology, Cedars Sinai Medical Center, Los Angeles, California, CA 90048, USA
Oncogene 21:4739-46. 2002....
- Amplification and overexpression of prosaposin in prostate cancerShahriar Koochekpour
Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
Genes Chromosomes Cancer 44:351-64. 2005....
- A prostatic intraepithelial neoplasia-dependent p27 Kip1 checkpoint induces senescence and inhibits cell proliferation and cancer progressionPradip K Majumder
Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
Cancer Cell 14:146-55. 2008..These data suggest that a p27(Kip1)-driven checkpoint limits progression of PIN to CaP...
- Myc-driven murine prostate cancer shares molecular features with human prostate tumorsKatharine Ellwood-Yen
Department of Medicine, and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
Cancer Cell 4:223-38. 2003..This approach illustrates how genomic technologies can be applied to mouse cancer models to guide evaluation of human tumor databases...
- Antitumor activity of rapamycin in a Phase I trial for patients with recurrent PTEN-deficient glioblastomaTim F Cloughesy
Department of Neurology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
PLoS Med 5:e8. 2008..Small, molecularly focused clinical studies offer the promise of the early definition of optimal biologic dose and patient population...
- Murine cell lines derived from Pten null prostate cancer show the critical role of PTEN in hormone refractory prostate cancer developmentJing Jiao
Department of Molecular and Medical Pharmacology, University of California at Los Angeles, Los Angeles, California 90095 1735, USA
Cancer Res 67:6083-91. 2007..These cell lines will serve as useful tools for understanding signaling pathways controlled by PTEN and elucidating the molecular mechanisms involved in hormone refractory prostate cancer formation...
- HER2/neu kinase-dependent modulation of androgen receptor function through effects on DNA binding and stabilityIngo K Mellinghoff
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA
Cancer Cell 6:517-27. 2004..Surprisingly, the downstream signaling pathway responsible for these effects appears to involve kinases other than Akt. These data suggest that the HER2/ERBB3 pathway is a critical target in hormone-refractory prostate cancer...
- Antibody-based profiling of the phosphoinositide 3-kinase pathway in clinical prostate cancerGeorge V Thomas
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California 90095, USA
Clin Cancer Res 10:8351-6. 2004..These three antibodies are potentially able to define a molecular signature of PTEN loss and/or AKT pathway activation in prostate cancer...
- Ligand-specific allosteric regulation of coactivator functions of androgen receptor in prostate cancer cellsSung Hee Baek
Department of Biological Sciences, Research Center for Functional Cellulomics, Seoul National University, South Korea
Proc Natl Acad Sci U S A 103:3100-5. 2006....
- Transcriptional regulation of a metastasis suppressor gene by Tip60 and beta-catenin complexesJung Hwa Kim
Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151 742, South Korea
Nature 434:921-6. 2005....
- NF-kappa B activates prostate-specific antigen expression and is upregulated in androgen-independent prostate cancerCharlie D Chen
Division of Hematology Oncology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095 1678, USA
Mol Cell Biol 22:2862-70. 2002..These results suggest a role of NF-kappa B in prostate cancer progression...
- MOUSE MODELS FOR HUMAN PROSTATE CANCERCharles Sawyers; Fiscal Year: 2007..abstract_text> ..
- Molecular Biology in Clinical Oncology WorkshopCharles Sawyers; Fiscal Year: 2007..Professional evaluation of the program is provided by Dr. Rebecca Lipner and Mr. Louis Grosso of the American Board of Internal Medicine. ..
- REGULATION OF THE PTEN GENE IN PROSTATE CANCERCharles Sawyers; Fiscal Year: 2001..Together, these experiments will define a novel mode of PTEN regulation in human cancers. ..
- STEM CELL GENES IN PROSTATE GROWTH AND DIFFERENTIATIONCharles Sawyers; Fiscal Year: 2001..These studies will enhance our understanding of the potential role of prostatic stem cell population in the normal and abnormal growth of the prostate that characterizes benign prostatic hypertrophy. ..