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Himisha Beltran, MD


Medical Oncology

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Physician

  • Physician
  • Associate Professor of Medicine, Harvard Medical School

Centers/Programs

Clinical Interests

  • Precision medicine
  • Prostate cancer

Diseases Treated

Contact Information

  • Appointments617-632-2682 (new)
    617-582-9725 (established)
  • Office Phone Number617-632-2429

Bio

Dr. Beltran is an Associate Professor of Medicine in the Lank Center for Genitourinary Oncology and the Division of Molecular and Cellular Oncology. She is also the Director of Translational Research within Medical Oncology.

Board Certification:

  • Hematology, 2011
  • Medical Oncology, 2011

Fellowship:

  • Weill Cornell Medical College

Residency:

  • University of Pennsylvania

Medical School:

  • New York Medical College

Recent Awards:

  • American Society of Clinical Investigation (ASCI) Young Physician-Scientist Award, 2017
  • Alliance for Clinical Trials in Oncology Scholar Awards in Honor of Dr. Emil “Tom” Frei III , 2014
  • Damon Runyon Cancer Research Foundation Clinical Investigator Award, 2013
  • Prostate Cancer Foundation Young Investigator Award, 2010

Research

The Beltran lab is focused on understanding mechanisms of treatment resistance in prostate cancer including lineage plasticity and the development of neuroendocrine prostate cancer
My lab is focused on understanding mechanisms of treatment resistance in advanced prostate cancer through the integration of clinical and molecular features of patients combined with preclinical modeling. We have focused on understanding mechanisms underlying an emerging subclass of androgen-indifferent prostate cancers that develop neuroendocrine features as an adaptive response mechanism upon selective therapeutic pressure of the androgen receptor (AR). We have used genomics and epigenomics to elucidate the molecular mechanisms driving evolution towards an AR-low state. We are developing tissue and circulating biomarkers and novel therapeutic strategies for clinical translation. Our mission is to make discoveries that improve the way we manage and treat patients with advanced prostate cancer.
In addition, within Dana Farber and through national and international collaborations, we work with a multidisciplinary team of scientists and clinicians towards the development of next generation molecular platforms and biomarkers for the clinical application of precision medicine across tumor types.

Transcriptional mediators of treatment resistance in lethal prostate cancer. Nat Med. 2021 03; 27(3):426-433.
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Activated ALK Cooperates with N-Myc via Wnt/ß-catenin Signaling to Induce Neuroendocrine Prostate Cancer. Cancer Res. 2021 Feb 26.
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Clinical considerations for the management of androgen indifferent prostate cancer. Prostate Cancer Prostatic Dis. 2021 Feb 10.
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Clinical and Biological Features of Neuroendocrine Prostate Cancer. Curr Oncol Rep. 2021 Jan 12; 23(2):15.
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Prostate Cancer Foundation Hormone-Sensitive Prostate Cancer Biomarker Working Group Meeting Summary. Urology. 2020 Dec 26.
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Common germline-somatic variant interactions in advanced urothelial cancer. Nat Commun. 2020 12 03; 11(1):6195.
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Integration of whole-exome and anchored PCR-based next generation sequencing significantly increases detection of actionable alterations in precision oncology. Transl Oncol. 2021 Jan; 14(1):100944.
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Role of specialized composition of SWI/SNF complexes in prostate cancer lineage plasticity. Nat Commun. 2020 11 03; 11(1):5549.
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Taxane-induced Attenuation of the CXCR2/BCL-2 Axis Sensitizes Prostate Cancer to Platinum-based Treatment. Eur Urol. 2020 Nov 02.
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Activity of Platinum-Based Chemotherapy in Patients With Advanced Prostate Cancer With and Without DNA Repair Gene Aberrations. JAMA Netw Open. 2020 10 01; 3(10):e2021692.
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Cancer and Leukemia Group B 90203 (Alliance): Radical Prostatectomy With or Without Neoadjuvant Chemohormonal Therapy in Localized, High-Risk Prostate Cancer. J Clin Oncol. 2020 09 10; 38(26):3042-3050.
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Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019. J Clin Oncol. 2020 08 20; 38(24):2798-2811.
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Small extracellular vesicles modulated by aVß3 integrin induce neuroendocrine differentiation in recipient cancer cells. J Extracell Vesicles. 2020 May 24; 9(1):1761072.
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ABEMUS: platform-specific and data-informed detection of somatic SNVs in cfDNA. Bioinformatics. 2020 05 01; 36(9):2665-2674.
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PIM protein kinases regulate the level of the long noncoding RNA H19 to control stem cell gene transcription and modulate tumor growth. Mol Oncol. 2020 05; 14(5):974-990.
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Circulating tumor DNA profile recognizes transformation to castration-resistant neuroendocrine prostate cancer. J Clin Invest. 2020 04 01; 130(4):1653-1668.
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SLFN11 Expression in Advanced Prostate Cancer and Response to Platinum-based Chemotherapy. Mol Cancer Ther. 2020 05; 19(5):1157-1164.
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Docetaxel for Early Prostate Cancer: What Have We Learned? Eur Urol. 2020 05; 77(5):573-575.
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Molecular Biomarkers in Localized Prostate Cancer: ASCO Guideline Summary. JCO Oncol Pract. 2020 06; 16(6):340-343.
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Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019. Eur Urol. 2020 04; 77(4):508-547.
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Androgen deprivation upregulates SPINK1 expression and potentiates cellular plasticity in prostate cancer. Nat Commun. 2020 01 20; 11(1):384.
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Genomic and clinical characterization of stromal infiltration markers in prostate cancer. Cancer. 2020 04 01; 126(7):1407-1412.
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Molecular Biomarkers in Localized Prostate Cancer: ASCO Guideline. J Clin Oncol. 2020 05 01; 38(13):1474-1494.
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Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015. Ann Oncol. 2019 12; 30(12):e3.
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Organotypic tumor slice cultures provide a versatile platform for immuno-oncology and drug discovery. Oncoimmunology. 2019; 8(12):e1670019.
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Towards precision oncology in advanced prostate cancer. Nat Rev Urol. 2019 11; 16(11):645-654.
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The Balancing Act: Assessing Treatment Burden Versus Treatment Benefit with Evolving Metastatic Hormone-sensitive Prostate Cancer Data. Eur Urol. 2019 12; 76(6):729-731.
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Integrative Molecular Analysis of Patients With Advanced and Metastatic Cancer. JCO Precis Oncol. 2019; 3.
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Clinical features of neuroendocrine prostate cancer. Eur J Cancer. 2019 11; 121:7-18.
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PARP Inhibition Suppresses GR-MYCN-CDK5-RB1-E2F1 Signaling and Neuroendocrine Differentiation in Castration-Resistant Prostate Cancer. Clin Cancer Res. 2019 11 15; 25(22):6839-6851.
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Proteomic and genomic signatures of repeat instability in cancer and adjacent normal tissues. Proc Natl Acad Sci U S A. 2019 08 20; 116(34):16987-16996.
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Cancer-Specific Thresholds Adjust for Whole Exome Sequencing-based Tumor Mutational Burden Distribution. JCO Precis Oncol. 2019; 3.
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The Role of Lineage Plasticity in Prostate Cancer Therapy Resistance. Clin Cancer Res. 2019 12 01; 25(23):6916-6924.
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Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling. Nat Commun. 2019 07 05; 10(1):2977.
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N-Myc-mediated epigenetic reprogramming drives lineage plasticity in advanced prostate cancer. J Clin Invest. 2019 07 01; 129(9):3924-3940.
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Publisher Correction: The long tail of oncogenic drivers in prostate cancer. Nat Genet. 2019 Jul; 51(7):1194.
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Erratum: CRIPTO overexpression promotes mesenchymal differentiation in prostate carcinoma cells through parallel regulation of AKT and FGFR activities. Oncotarget. 2019 06 25; 10(41):4247-4248.
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Transcriptomic and Clinical Characterization of Neuropeptide Y Expression in Localized and Metastatic Prostate Cancer: Identification of Novel Prostate Cancer Subtype with Clinical Implications. Eur Urol Oncol. 2019 07; 2(4):405-412.
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Retinoblastoma Loss in Cancer: Casting a Wider Net. Clin Cancer Res. 2019 07 15; 25(14):4199-4201.
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CHD1 Loss Alters AR Binding at Lineage-Specific Enhancers and Modulates Distinct Transcriptional Programs to Drive Prostate Tumorigenesis. Cancer Cell. 2019 May 13; 35(5):817-819.
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Genomic correlates of clinical outcome in advanced prostate cancer. Proc Natl Acad Sci U S A. 2019 06 04; 116(23):11428-11436.
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Ultrasensitive detection of cancer biomarkers by nickel-based isolation of polydisperse extracellular vesicles from blood. EBioMedicine. 2019 May; 43:114-126.
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Phase 1/2 study of fractionated dose lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 (177 Lu-J591) for metastatic castration-resistant prostate cancer. Cancer. 2019 08 01; 125(15):2561-2569.
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Exceptional Response to Pembrolizumab in a Patient With Castration-Resistant Prostate Cancer With Pancytopenia From Myelophthisis. J Oncol Pract. 2019 06; 15(6):343-345.
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CHD1 Loss Alters AR Binding at Lineage-Specific Enhancers and Modulates Distinct Transcriptional Programs to Drive Prostate Tumorigenesis. Cancer Cell. 2019 04 15; 35(4):603-617.e8.
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Delta-like protein 3 expression and therapeutic targeting in neuroendocrine prostate cancer. Sci Transl Med. 2019 03 20; 11(484).
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Increased Serine and One-Carbon Pathway Metabolism by PKC?/? Deficiency Promotes Neuroendocrine Prostate Cancer. Cancer Cell. 2019 03 18; 35(3):385-400.e9.
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Identification of a therapeutic target using molecular sequencing for treatment of recurrent uterine serous adenocarcinoma. Gynecol Oncol Rep. 2019 May; 28:54-57.
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Biological Evolution of Castration-resistant Prostate Cancer. Eur Urol Focus. 2019 03; 5(2):147-154.
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Neuroendocrine Differentiation in Prostate Cancer: Emerging Biology, Models, and Therapies. Cold Spring Harb Perspect Med. 2019 02 01; 9(2).
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The application of precision medicine in diagnosing familial Mediterranean fever. Leuk Lymphoma. 2019 08; 60(8):2091-2093.
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ONECUT2 is a driver of neuroendocrine prostate cancer. Nat Commun. 2019 01 17; 10(1):278.
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Low Tristetraprolin Expression Is Associated with Lethal Prostate Cancer. Cancer Epidemiol Biomarkers Prev. 2019 03; 28(3):584-590.
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Immunogenomic analyses associate immunological alterations with mismatch repair defects in prostate cancer. J Clin Invest. 2018 11 01; 128(11):5185.
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Publisher Correction: Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature. 2018 11; 563(7731):E24.
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Plasma androgen receptor and serum chromogranin A in advanced prostate cancer. Sci Rep. 2018 10 18; 8(1):15442.
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CD38 is methylated in prostate cancer and regulates extracellular NAD. Cancer Metab. 2018; 6:13.
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A Phase II Trial of the Aurora Kinase A Inhibitor Alisertib for Patients with Castration-resistant and Neuroendocrine Prostate Cancer: Efficacy and Biomarkers. Clin Cancer Res. 2019 01 01; 25(1):43-51.
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The Role of Next-Generation Sequencing in Precision Medicine: A Review of Outcomes in Oncology. J Pers Med. 2018 Sep 17; 8(3).
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Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses. Nat Commun. 2018 09 06; 9(1):3600.
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Immunogenomic analyses associate immunological alterations with mismatch repair defects in prostate cancer. J Clin Invest. 2018 10 01; 128(10):4441-4453.
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Biallelic tumour suppressor loss and DNA repair defects in de novo small-cell prostate carcinoma. J Pathol. 2018 10; 246(2):244-253.
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Evolving Intersection Between Inherited Cancer Genetics and Therapeutic Clinical Trials in Prostate Cancer: A White Paper From the Germline Genetics Working Group of the Prostate Cancer Clinical Trials Consortium. JCO Precis Oncol. 2018; 2018.
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Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study. J Clin Oncol. 2018 08 20; 36(24):2492-2503.
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Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature. 2018 08; 560(7719):499-503.
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BRCA2-Associated Prostate Cancer in a Patient With Spinal and Bulbar Muscular Atrophy. JCO Precis Oncol. 2018; 2.
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Patient derived organoids to model rare prostate cancer phenotypes. Nat Commun. 2018 06 19; 9(1):2404.
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The long noncoding RNA landscape of neuroendocrine prostate cancer and its clinical implications. Gigascience. 2018 06 01; 7(6).
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CATCH-KB: Establishing a Pharmacogenomics Variant Repository for Chemotherapy-Induced Cardiotoxicity. AMIA Jt Summits Transl Sci Proc. 2018; 2017:168-177.
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The long tail of oncogenic drivers in prostate cancer. Nat Genet. 2018 05; 50(5):645-651.
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Cellular plasticity and the neuroendocrine phenotype in prostate cancer. Nat Rev Urol. 2018 05; 15(5):271-286.
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Clinical Outcome of Prostate Cancer Patients with Germline DNA Repair Mutations: Retrospective Analysis from an International Study. Eur Urol. 2018 05; 73(5):687-693.
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Naming disease states for clinical utility in prostate cancer: a rose by any other name might not smell as sweet. Ann Oncol. 2018 01 01; 29(1):23-25.
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Bone biopsy protocol for advanced prostate cancer in the era of precision medicine. Cancer. 2018 03 01; 124(5):1008-1015.
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Aberrant Activation of a Gastrointestinal Transcriptional Circuit in Prostate Cancer Mediates Castration Resistance. Cancer Cell. 2017 Dec 11; 32(6):792-806.e7.
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Rapid autopsy of a patient with recurrent anaplastic ependymoma. Palliat Support Care. 2018 04; 16(2):238-242.
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Impact of Therapy on Genomics and Transcriptomics in High-Risk Prostate Cancer Treated with Neoadjuvant Docetaxel and Androgen Deprivation Therapy. Clin Cancer Res. 2017 Nov 15; 23(22):6802-6811.
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Management of Patients with Advanced Prostate Cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017. Eur Urol. 2018 02; 73(2):178-211.
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Next-Generation Rapid Autopsies Enable Tumor Evolution Tracking and Generation of Preclinical Models. JCO Precis Oncol. 2017; 2017.
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Biology and evolution of poorly differentiated neuroendocrine tumors. Nat Med. 2017 Jun 06; 23(6):1-10.
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A germline FANCA alteration that is associated with increased sensitivity to DNA damaging agents. Cold Spring Harb Mol Case Stud. 2017 Sep; 3(5).
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Erratum to: Unraveling the clonal hierarchy of somatic genomic aberrations. Genome Biol. 2017 05 02; 18(1):80.
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Transplantation of engineered organoids enables rapid generation of metastatic mouse models of colorectal cancer. Nat Biotechnol. 2017 06; 35(6):577-582.
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Emerging Variants of Castration-Resistant Prostate Cancer. Curr Oncol Rep. 2017 May; 19(5):32.
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On-site Cytology for Development of Patient-Derived Three-dimensional Organoid Cultures - A Pilot Study. Anticancer Res. 2017 04; 37(4):1569-1573.
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Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine. Cancer Discov. 2017 05; 7(5):462-477.
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The clone wars. Sci Transl Med. 2017 02 15; 9(377).
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SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer. Science. 2017 01 06; 355(6320):84-88.
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Unleashing the wrath of Ras. Sci Transl Med. 2017 01 04; 9(371).
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Prostate cancer in 2016: Improved outcomes and precision medicine come within reach. Nat Rev Urol. 2017 Feb; 14(2):71-72.
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Personalizing Therapy for Metastatic Prostate Cancer: The Role of Solid and Liquid Tumor Biopsies. Am Soc Clin Oncol Educ Book. 2017; 37:358-369.
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Synthetic lethality and beyond. Sci Transl Med. 2016 11 16; 8(365):365ec182.
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The Master Neural Transcription Factor BRN2 Is an Androgen Receptor-Suppressed Driver of Neuroendocrine Differentiation in Prostate Cancer. Cancer Discov. 2017 01; 7(1):54-71.
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Clonal evolution of chemotherapy-resistant urothelial carcinoma. Nat Genet. 2016 12; 48(12):1490-1499.
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N-Myc Induces an EZH2-Mediated Transcriptional Program Driving Neuroendocrine Prostate Cancer. Cancer Cell. 2016 10 10; 30(4):563-577.
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Development and validation of a whole-exome sequencing test for simultaneous detection of point mutations, indels and copy-number alterations for precision cancer care. NPJ Genom Med. 2016; 1.
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Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J Med. 2016 Aug 04; 375(5):443-53.
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Update on the biology and management of neuroendocrine prostate cancer. Clin Adv Hematol Oncol. 2016 Jul; 14(7):513-5.
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SRRM4 Drives Neuroendocrine Transdifferentiation of Prostate Adenocarcinoma Under Androgen Receptor Pathway Inhibition. Eur Urol. 2017 01; 71(1):68-78.
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Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015. Ann Oncol. 2019 12; 30(12):e3.
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PO-43 - Differential coagulation factor expression in neuroendocrine prostate cancer (PC), metastatic castrate-resistant PC, and localized prostatic adenocarcinoma. Thromb Res. 2016 Apr; 140 Suppl 1:S192.
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Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat Med. 2016 Mar; 22(3):298-305.
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Emerging Molecular Biomarkers in Advanced Prostate Cancer: Translation to the Clinic. Am Soc Clin Oncol Educ Book. 2016; 35:131-41.
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The Initial Detection and Partial Characterization of Circulating Tumor Cells in Neuroendocrine Prostate Cancer. Clin Cancer Res. 2016 Mar 15; 22(6):1510-9.
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An emerging role for cytopathology in precision oncology. Cancer Cytopathol. 2016 Mar; 124(3):167-73.
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The Placental Gene PEG10 Promotes Progression of Neuroendocrine Prostate Cancer. Cell Rep. 2015 Aug 11; 12(6):922-36.
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Prostate cancer: Intrapatient heterogeneity in prostate cancer. Nat Rev Urol. 2015 Aug; 12(8):430-1.
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Integrative Clinical Genomics of Advanced Prostate Cancer. Cell. 2015 Jul 16; 162(2):454.
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Whole-Exome Sequencing of Metastatic Cancer and Biomarkers of Treatment Response. JAMA Oncol. 2015 Jul; 1(4):466-74.
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Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015. Ann Oncol. 2015 Aug; 26(8):1589-604.
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Integrative clinical genomics of advanced prostate cancer. Cell. 2015 May 21; 161(5):1215-1228.
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CRIPTO overexpression promotes mesenchymal differentiation in prostate carcinoma cells through parallel regulation of AKT and FGFR activities. Oncotarget. 2015 May 20; 6(14):11994-2008.
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Prioritizing precision medicine for prostate cancer. Ann Oncol. 2015 Jun; 26(6):1041-1042.
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The spectrum of neuroendocrine tumors: histologic classification, unique features and areas of overlap. Am Soc Clin Oncol Educ Book. 2015; 92-103.
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ERG induces taxane resistance in castration-resistant prostate cancer. Nat Commun. 2014 Nov 25; 5:5548.
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The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer. Nat Commun. 2014 Nov 21; 5:5383.
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Organoid cultures derived from patients with advanced prostate cancer. Cell. 2014 Sep 25; 159(1):176-187.
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Unraveling the clonal hierarchy of somatic genomic aberrations. Genome Biol. 2014 Aug 26; 15(8):439.
View in: PubMed

Exploring the role of anti-angiogenic therapies in prostate cancer: results from the phase 3 trial of sunitinib. Asian J Androl. 2014 Jul-Aug; 16(4):568-9.
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Prostate cancer with Paneth cell-like neuroendocrine differentiation has recognizable histomorphology and harbors AURKA gene amplification. Hum Pathol. 2014 Oct; 45(10):2136-43.
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Proposed morphologic classification of prostate cancer with neuroendocrine differentiation. Am J Surg Pathol. 2014 Jun; 38(6):756-67.
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Aggressive variants of castration-resistant prostate cancer. Clin Cancer Res. 2014 Jun 01; 20(11):2846-50.
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The many faces of neuroendocrine differentiation in prostate cancer progression. Front Oncol. 2014; 4:60.
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The N-myc Oncogene: Maximizing its Targets, Regulation, and Therapeutic Potential. Mol Cancer Res. 2014 Jun; 12(6):815-22.
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High fidelity patient-derived xenografts for accelerating prostate cancer discovery and drug development. Cancer Res. 2014 Feb 15; 74(4):1272-83.
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Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013 Nov; 31(11):1023-31.
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Cross modulation between the androgen receptor axis and protocadherin-PC in mediating neuroendocrine transdifferentiation and therapeutic resistance of prostate cancer. Neoplasia. 2013 Jul; 15(7):761-72.
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Punctuated evolution of prostate cancer genomes. Cell. 2013 Apr 25; 153(3):666-77.
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Epigenomic alterations in localized and advanced prostate cancer. Neoplasia. 2013 Apr; 15(4):373-83.
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DNA mismatch repair in prostate cancer. J Clin Oncol. 2013 May 10; 31(14):1782-4.
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Concurrent AURKA and MYCN gene amplifications are harbingers of lethal treatment-related neuroendocrine prostate cancer. Neoplasia. 2013 Jan; 15(1):1-10.
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New strategies in prostate cancer: translating genomics into the clinic. Clin Cancer Res. 2013 Feb 01; 19(3):517-23.
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Epigenetic repression of miR-31 disrupts androgen receptor homeostasis and contributes to prostate cancer progression. Cancer Res. 2013 Feb 01; 73(3):1232-44.
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Challenges in recognizing treatment-related neuroendocrine prostate cancer. J Clin Oncol. 2012 Dec 20; 30(36):e386-9.
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Targeted next-generation sequencing of advanced prostate cancer identifies potential therapeutic targets and disease heterogeneity. Eur Urol. 2013 May; 63(5):920-6.
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From sequence to molecular pathology, and a mechanism driving the neuroendocrine phenotype in prostate cancer. J Pathol. 2012 Jul; 227(3):286-97.
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Editorial comment. J Urol. 2012 Jul; 188(1):108-9.
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Identification of functionally active, low frequency copy number variants at 15q21.3 and 12q21.31 associated with prostate cancer risk. Proc Natl Acad Sci U S A. 2012 Apr 24; 109(17):6686-91.
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Next generation sequencing of prostate cancer from a patient identifies a deficiency of methylthioadenosine phosphorylase, an exploitable tumor target. . 2012 Mar; 11(3):775-83.
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Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer Discov. 2011 Nov; 1(6):487-95.
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Novel therapeutics for the management of castration-resistant prostate cancer (CRPC). BJU Int. 2012 Apr; 109(7):968-85.
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Abiraterone plus prednisone improves survival in metastatic castration-resistant prostate cancer. Asian J Androl. 2011 Nov; 13(6):785-6.
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New therapies for castration-resistant prostate cancer: efficacy and safety. Eur Urol. 2011 Aug; 60(2):279-90.
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Primary squamous cell carcinoma of the urinary bladder presenting as peritoneal carcinomatosis. Adv Urol. 2010; 179250.
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Anti-prostate-specific membrane antigen-based radioimmunotherapy for prostate cancer. Cancer. 2010 Feb 15; 116(4 Suppl):1075-83.
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