Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Oncology Reports
Published in: Current Oncology Reports 5/2017

01-05-2017 | Genitourinary Cancers (DP Petrylak and JW Kim, Section Editors)

Emerging Variants of Castration-Resistant Prostate Cancer

Authors: Panagiotis J. Vlachostergios, Loredana Puca, Himisha Beltran

Published in: Current Oncology Reports | Issue 5/2017

Login to get access

Abstract

Metastatic castration-resistant prostate cancer (CRPC) is associated with substantial clinical, pathologic, and molecular heterogeneity. Most tumors remain driven by androgen receptor (AR) signaling, which has clinical implications for patient selection for AR-directed approaches. However, histologic and clinical resistance phenotypes can emerge after AR inhibition, in which the tumors become less dependent on the AR. In this review, we discuss prostate cancer variants including neuroendocrine (NEPC) and aggressive variant (AVPC) prostate cancers and their clinical implications. Improvements in the understanding of the biologic mechanisms and molecular features underlying prostate cancer variants may help prognostication and facilitate the development of novel therapeutic approaches for subclasses of patient with CRPC.
Literature
1.
Weischenfeldt J, Simon R, Feuerbach L, Schlangen K, Weichenhan D, Minner S, et al. Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer. Cancer Cell. 2013;23(2):159–70.CrossRefPubMed
2.
Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J Clin. 1972;22(4):232–40.CrossRefPubMed
3.
Kirby M, Hirst C, Crawford ED. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract. 2011;65(11):1180–92.CrossRefPubMed
4.
Cookson MS, Roth BJ, Dahm P, Engstrom C, Freedland SJ, Hussain M, et al. Castration-resistant prostate cancer: AUA Guideline. J Urol. 2013;190(2):429–38.CrossRefPubMed
5.
Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014;65(2):467–79.CrossRefPubMed
6.
Roviello G, Sigala S, Sandhu S, Bonetta A, Cappelletti MR, Zanotti L, et al. Role of the novel generation of androgen receptor pathway targeted agents in the management of castration-resistant prostate cancer: a literature based meta-analysis of randomized trials. Eur J Cancer. 2016;61:111–21.CrossRefPubMed
7.
• Watson PA, Arora VK, Sawyers CL. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat Rev Cancer. 2015;15(12):701–11. Comprehensive review of mechanisms of resistance in CRPC
8.
Graham L, Schweizer MT. Targeting persistent androgen receptor signaling in castration-resistant prostate cancer. Med Oncol. 2016;33(5):44.CrossRefPubMed
9.
• Crawford ED, Higano CS, Shore ND, Hussain M, Petrylak DP. Treating patients with metastatic castration resistant prostate cancer: a comprehensive review of available therapies. J Urol. 2015;194(6):1537–47. Comprehensive review of currently approved therapies in CRPC CrossRefPubMed
10.
•• Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med. 2015;373(18):1697–708. First biomarker-driven phase 2 trial in mCRPC patients showing significant responses in patients with BRCA2 and ATM DNA repair defects CrossRefPubMedPubMedCentral
11.
Fraser M, Berlin A, Bristow RG, van der Kwast T. Genomic, pathological, clinical heterogeneity as drivers of personalized medicine in prostate cancer. Urol Oncol. 2015;33(2):85–94.CrossRefPubMed
12.
McKay RR, Zukotynski KA, Werner L, Voznesensky O, Wu JS, Smith SE, et al. Imaging, procedural and clinical variables associated with tumor yield on bone biopsy in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2014;17(4):325–31.CrossRefPubMedPubMedCentral
13.
•• Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015;161(5):1215–28. The first multi-institutional, comprehensive assessment of whole-exome and transcriptome sequencing from mCRPC lesions revealed the most common gene aberrations, involving AR, ETS, TP53, and PTEN and DNA repair genes CrossRefPubMedPubMedCentral
14.
•• Small EJ, Aggarwal RR, Huang J, Sokolov A, Zhang L, Alumkal JJ, et al. Clinical and genomic characterization of metastatic small cell/neuroendocrine prostate cancer (SCNC) and intermediate atypical prostate cancer (IAC): results from the SU2C/PCF/AACRWest Coast Prostate Cancer Dream Team (WCDT). J Clin Oncol. 2016;34 (suppl; abstr 5019). The identification and characterization of a new pathologic subtype, IAC, in mCRPC patients resistant to ABT or ENZ. The majority of CRPC metastases were found to display non-adenocarcinoma features, associated with a shortened survival. IAC was found to have a distinct transcriptional signature compared to classic adenocarcinoma and SCPC and an intermediate median survival .
15.
Zong Y, Goldstein AS. Adaptation or selection—mechanisms of castration-resistant prostate cancer. Nat Rev Urol. 2013;10(2):90–8.CrossRefPubMed
16.
• Epstein JI, Amin MB, Beltran H, Lotan TL, Mosquera JM, Reuter VE, et al. Proposed morphologic classification of prostate cancer with neuroendocrine differentiation. Am J Surg Pathol. 2014;38(6):756–67. Refined diagnostic terminology describing the full spectrum of NE differentiation in 5 different pathological entities CrossRefPubMedPubMedCentral
17.
Parimi V, Goyal R, Poropatich K, Yang XJ. Neuroendocrine differentiation of prostate cancer: a review. Am J Clin Exp Urol. 2014;2(4):273–85.PubMedPubMedCentral
18.
19.
Wang W, Epstein JI. Small cell carcinoma of the prostate. A morphologic and immunohistochemical study of 95 cases. Am J Surg Pathol. 2008;32(1):65–71.CrossRefPubMed
20.
Scheble VJ, Braun M, Wilbertz T, Stiedl AC, Petersen K, Schilling D, et al. ERG rearrangement in small cell prostatic and lung cancer. Histopathology. 2010;56(7):937–43.CrossRefPubMed
21.
Lotan TL, Gupta NS, Wang W, Toubaji A, Haffner MC, Chaux A, et al. ERG gene rearrangements are common in prostatic small cell carcinomas. Mod Pathol. 2011;24(6):820–8.CrossRefPubMedPubMedCentral
22.
Papandreou CN, Daliani DD, Thall PF, Tu SM, Wang X, Reyes A, et al. Results of a phase II study with doxorubicin, etoposide, and cisplatin in patients with fully characterized small-cell carcinoma of the prostate. J Clin Oncol. 2002;20(14):3072–80.CrossRefPubMed
23.
Wang HT, Yao YH, Li BG, Tang Y, Chang JW, Zhang J. Neuroendocrine Prostate Cancer (NEPC) progressing from conventional prostatic adenocarcinoma: factors associated with time to development of NEPC and survival from NEPC diagnosis-a systematic review and pooled analysis. J Clin Oncol. 2014;32(30):3383–90.CrossRefPubMed
24.
Deorah S, Rao MB, Raman R, Gaitonde K, Donovan JF. Survival of patients with small cell carcinoma of the prostate during 1973-2003: a population-based study. BJU Int. 2012;109(6):824–30.CrossRefPubMed
25.
•• Beltran H, Rickman DS, Park K, Chae SS, Sboner A, MacDonald TY, et al. Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer Discov. 2011;1(6):487–95.CrossRefPubMedPubMedCentral
26.
•• Lee JK, Phillips JW, Smith BA, Park JW, Stoyanova T, McCaffrey EF, et al. N-Myc drives neuroendocrine prostate cancer initiated from human prostate epithelial cells. Cancer Cell. 2016;29(4):536–47. Identification of N-Myc and activated AKT1 as oncogenic transformers of CRPC cells to NEPC with foci of divergent differentiation from adenocarcinoma. CrossRefPubMedPubMedCentral
27.
•• Dardenne E, Beltran H, Benelli M, Gayvert K, Berger A, Puca L, et al. N-Myc induces an EZH2-mediated transcriptional program driving neuroendocrine prostate cancer. Cancer Cell. 2016;30(4):563–77. Functional characterization of the role of N-myc as a driver of NE differentiation via EZH2-mediated repression of AR signaling and sensitization to EZH2 and AURKA inhibitors.
28.
Otto T, Horn S, Brockmann M, Eilers U, Schüttrumpf L, Popov N, et al. Stabilization of N-Myc is a critical function of aurora A in human neuroblastoma. Cancer Cell. 2009;15(1):67–78.CrossRefPubMed
29.
Brockmann M, Poon E, Berry T, Carstensen A, Deubzer HE, Rycak L, et al. Small molecule inhibitors of aurora-a induce proteasomal degradation of N-myc in childhood neuroblastoma. Cancer Cell. 2013;24(1):75–89.CrossRefPubMedPubMedCentral
30.
Gustafson WC, Meyerowitz JG, Nekritz EA, Chen J, Benes C, Charron E, et al. Drugging MYCN through an allosteric transition in aurora kinase A. Cancer Cell. 2014;26(3):414–27.CrossRefPubMedPubMedCentral
31.
Dominguez-Brauer C, Thu KL, Mason JM, Blaser H, Bray MR, Mak TW. Targeting mitosis in cancer: emerging strategies. Mol Cell. 2015;60(4):524–36.CrossRefPubMed
32.
Li Z, Sun Y, Chen X, Squires J, Nowroozizadeh B, Liang C, et al. p53 mutation directs AURKA overexpression via miR-25 and FBXW7 in prostatic small cell neuroendocrine carcinoma. Mol Cancer Res. 2015;13(3):584–91.CrossRefPubMed
33.
•• Beltran H, Prandi D, Mosquera JM, Benelli M, Puca L, Cyrta J, et al. Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat Med. 2016;22(3):298–305. Integrative molecular analysis of NEPC. Whole exome sequencing provided evidence of divergent clonal evolution of adenocarcinoma to NEPC.
34.
35.
Tan HL, Sood A, Rahimi HA, Wang W, Gupta N, Hicks J, et al. Rb loss is characteristic of prostatic small cell neuroendocrine carcinoma. Clin Cancer Res. 2014;20(4):890–903.CrossRefPubMed
36.
Zhou Z, Flesken-Nikitin A, Corney DC, Wang W, Goodrich DW, Roy-Burman P, et al. Synergy of p53 and Rb deficiency in a conditional mouse model for metastatic prostate cancer. Cancer Res. 2006;66(16):7889–98.CrossRefPubMed
37.
Bianchi-Frias D, Hernandez SA, Coleman R, Wu H, Nelson PS. The landscape of somatic chromosomal copy number aberrations in GEM models of prostate carcinoma. Mol Cancer Res. 2015;13(2):339–47.CrossRefPubMed
38.
•• Mu P, Zhang Z, Benelli M, Karthaus WR, Hoover E, Chen CC, et al. SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer. Science. 2017;355(6320):84–8. Combined Rb1 and TP53 loss is associated with loss of luminal features, lineage plasticity, and enzalutamide-resistance, and this is mediated by the reprogramming factor SOX2 CrossRefPubMedPubMedCentral
39.
•• Ku SY, Rosario S, Wang Y, Mu P, Seshadri M, Goodrich ZW, et al. Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. Science. 2017;355(6320):78–83. Loss of Rb1 and Trp53 is associated with propagation of lineage plasticity and emergence of NE phenotypes mediated by epigenetic reprogramming through EZH2 which confers antiandrogen therapy resistance and can be reversed by EZH2 inhibition in CRPC and NEPC models
40.
•• Bishop JL, Thaper D, Vahid S, Jama R, Ketola K, Kim S, et al. The master neural transcription factor BRN2 is an androgen receptor suppressed driver of neuroendocrine differentiation in prostate cancer. Cancer Discov. 2017;7(1):54–71. Mechanistic link between AR and the master regulator of neuronal differentiation, POU-domain transcription factor BRN2. In context of enzalutamide resistance and an AR-low phenotype, suppression of BRN2 is lost and BRN2 thereby drives neuroendocrine differentiation and aggressive disease CrossRefPubMed
41.
Arora VK, Schenkein E, Murali R, Subudhi SK, Wongvipat J, Balbas MD, et al. Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell. 2013;155(6):1309–22.CrossRefPubMedPubMedCentral
42.
Lin D, Wyatt AW, Xue H, Wang Y, Dong X, Haegert A, et al. High fidelity patient-derived xenografts for accelerating prostate cancer discovery and drug development. Cancer Res. 2014;74(4):1272–83.CrossRefPubMed
43.
Zhang X, Coleman IM, Brown LG, True LD, Kollath L, Lucas JM, et al. SRRM4 expression and the loss of REST activity may promote the emergence of the neuroendocrine phenotype in castration-resistant prostate cancer. Clin Cancer Res. 2015;21(20):4698–708.CrossRefPubMedPubMedCentral
44.
Gao D, Vela I, Sboner A, Iaquinta PJ, Karthaus WR, Gopalan A, et al. Organoid cultures derived from patients with advanced prostate cancer. Cell. 2014;159(1):176–87.CrossRefPubMedPubMedCentral
45.
Pauli C, Puca L, Mosquera JM, Robinson BD, Beltran H, Rubin MA, et al. An emerging role for cytopathology in precision oncology. Cancer Cytopathol. 2016;124(3):167–73.CrossRefPubMed
46.
Lapuk AV, Wu C, Wyatt AW, McPherson A, McConeghy BJ, Brahmbhatt S, et al. From sequence to molecular pathology, and a mechanism driving the neuroendocrine phenotype in prostate cancer. J Pathol. 2012;227(3):286–97.CrossRefPubMedPubMedCentral
47.
Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS, et al. Integrative genomic profiling of human prostate cancer. Cancer Cell. 2010;18(1):11–22.CrossRefPubMedPubMedCentral
48.
•• Li Y, Donmez N, Sahinalp C, Xie N, Wang Y, Xue H, et al. SRRM4 drives neuroendocrine transdifferentiation of prostate adenocarcinoma under androgen receptor pathway inhibition. Eur Urol. 2016. Identification of a NEPC-specific mRNA splicing signature driven by SRRM4, inducing NE transdifferentiation through REST1 alternative splicing-associated downregulation, in 2 independent CRPC-NEPC patient cohorts .
49.
•• Akamatsu S, Wyatt AW, Lin D, Lysakowski S, Zhang F, Kim S, et al. The placental gene PEG10 promotes progression of neuroendocrine prostate cancer. Cell Rep. 2015;12(6):922–36. Identification of PEG10 involvement in NEPC transdifferentiation and invasion through transcriptional re-expression and translational stabilization of PEG10 via AR-, p53- and RB1/E2F1-dependent mechanisms in patient-derived xenografts CrossRefPubMed
50.
Mounir Z, Lin F, Lin VG, Korn JM, Yu Y, Valdez R, et al. TMPRSS2:ERG blocks neuroendocrine and luminal cell differentiation to maintain prostate cancer proliferation. Oncogene. 2015;34(29):3815–25.CrossRefPubMed
51.
Tzelepi V, Zhang J, Lu JF, Kleb B, Wu G, Wan X, et al. Modeling a lethal prostate cancer variant with small-cell carcinoma features. Clin Cancer Res. 2012;18(3):666–77.CrossRefPubMed
52.
• Tsai H, Morais CL, Alshalalfa M, Tan HL, Haddad Z, Hicks J, et al. Cyclin D1 loss distinguishes prostatic small-cell carcinoma from most prostatic adenocarcinomas. Clin Cancer Res. 2015;21(24):5619–29. A high ratio of CDKN2A to CCND1 expression and loss of cyclin D1 protein expression are associated with underlying Rb functional loss and distinguish morphologically identified SCPC from adenocarcinoma in 2 distinct rapid autopsy mCRPC patient cohorts and PDX CrossRefPubMedPubMedCentral
53.
•• Aparicio AM, Harzstark AL, Corn PG, Wen S, Araujo JC, Tu SM, et al. Platinum-based chemotherapy for variant castrate-resistant prostate cancer. Clin Cancer Res. 2013;19(13):3621–30. First phase 2 evidence of platinum-based chemotherapy efficacy in AVPC with 7 clinically defined criteria, based on SCPC characteristics
54.
•• Aparicio AM, Shen L, Tapia EL, Lu JF, Chen HC, Zhang J, et al. Combined tumor suppressor defects characterize clinically defined aggressive variant prostate cancers. Clin Cancer Res. 2016;22(6):1520–30. Combined alterations in RB1, Tp53, and/or PTEN copy number losses in AVPC clinical trial patients and AVPC PDX model were identified as the strongest discriminators between AVPC and unselected mCRPC patients from other cohorts CrossRefPubMed
55.
• Corn PG, Li-Ning-Tapia E, Xiao L, Heath EI, Chancoco H, Hoang A, et al. Confirmatory analysis to determine associations between platinum-sensitivity, molecular signature of combined tumor suppressor defects and aggressive variant prostate carcinomas (AVPC). J Clin Oncol. 2016;34 (suppl; abstr 5020). Activity of cabazitaxel-carboplatin combination with evidence of PFS benefit in AVPC patients.
56.
Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H, et al. Inherited DNA repair gene mutations in men with metastatic prostate cancer, New England Journal of Medicine. N Engl J Med. 2016;375(5):443–53.CrossRefPubMedPubMedCentral
57.
Small EJ, Huang J, Youngren J, Sokolov A, Aggarwal RR, Thomas G, et al. Characterization of neuroendocrine prostate cancer (NEPC) in patients with metastatic castration resistant prostate cancer (mCRPC) resistant to abiraterone (Abi) or enzalutamide (Enz): Preliminary results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT). J Clin Oncol. 2015;33 (suppl; abstr 5003)
58.
•• Smith BA, Sokolov A, Uzunangelov V, Baertsch R, Newton Y, Graim K, et al. A basal stem cell signature identifies aggressive prostate cancer phenotypes. Proc Natl Acad Sci U S A. 2015;112(47):E6544–52. First evidence of a conserved, E2F-driven, stemness transcriptional program between primary prostate basal cells and small cell NEPC cells after comparison with independent mCRPC patient cohorts CrossRefPubMedPubMedCentral
59.
Beltran H, Tomlins S, Aparicio A, Arora V, Rickman D, Ayala G, et al. Aggressive variants of castration-resistant prostate cancer. Clin Cancer Res. 2014;20(11):2846–50.CrossRefPubMedPubMedCentral
60.
Marcus DM, Goodman M, Jani AB, Osunkoya AO, Rossi PJ. A comprehensive review of incidence and survival in patients with rare histological variants of prostate cancer in the United States from 1973 to 2008. Prostate Cancer Prostatic Dis. 2012;15(3):283–8.CrossRefPubMed
61.
Tu SM, Lopez A, Leibovici D, Bilen MA, Evliyaoglu F, Aparicio A, et al. Ductal adenocarcinoma of the prostate: clinical features and implications after local therapy. Cancer. 2009;115(13):2872–80.CrossRefPubMed
62.
Han B, Mehra R, Suleman K, Tomlins SA, Wang L, Singhal N, et al. Characterization of ETS gene aberrations in select histologic variants of prostate carcinoma. Mod Pathol. 2009;22(9):1176–85.CrossRefPubMedPubMedCentral
63.
• Schweizer MT, Cheng HH, Tretiakova MS, Vakar-Lopez F, Klemfuss N, Konnick EQ, et al. Mismatch repair deficiency may be common in ductal adenocarcinoma of the prostate. Oncotarget. 2016; doi:10.​18632/​oncotarget.​12697. Description of clinical and genomic characteristics of patient series with ductal prostate adenocarcinoma
64.
65.
Halabi S, Kelly WK, Ma H, Zhou H, Solomon NC, Fizazi K, et al. Meta-analysis evaluating the impact of site of metastasis on overall survival in men with castration-resistant prostate cancer. J Clin Oncol. 2016;34(14):1652–9.CrossRefPubMedPubMedCentral
66.
Zhang T, Armstrong AJ. Clinical phenotypes of castration-resistant prostate cancer. Clin Adv Hematol Oncol. 2013;11(11):707–18.PubMed
67.
Halabi S, Lin CY, Kelly WK, Fizazi KS, Moul JW, Kaplan EB, et al. Updated prognostic model for predicting overall survival in first-line chemotherapy for patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2014;32(7):671–7.CrossRefPubMedPubMedCentral
68.
de Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2008;14(19):6302–9.CrossRefPubMed
69.
Scher HI, Heller G, Molina A, Attard G, Danila DC, Jia X, et al. Circulating tumor cell biomarker panel as an individual-level surrogate for survival in metastatic castration-resistant prostate cancer. J Clin Oncol. 2015;33(12):1348–55.CrossRefPubMedPubMedCentral
70.
Miyamoto DT, Lee RJ, Stott SL, Ting DT, Wittner BS, Ulman M, et al. Androgen receptor signaling in circulating tumor cells as a marker of hormonally responsive prostate cancer. Cancer Discov. 2012;2(11):995–1003.CrossRefPubMedPubMedCentral
71.
Crespo M, van Dalum G, Ferraldeschi R, Zafeiriou Z, Sideris S, Lorente D, et al. Androgen receptor expression in circulating tumour cells from castration-resistant prostate cancer patients treated with novel endocrine agents. Br J Cancer. 2015;112(7):1166–74.CrossRefPubMedPubMedCentral
72.
Marín-Aguilera M, Reig Ò, Lozano JJ, Jiménez N, García-Recio S, Erill N, et al. Molecular profiling of peripheral blood is associated with circulating tumor cells content and poor survival in metastatic castration-resistant prostate cancer. Oncotarget. 2015;6(12):10604–16.CrossRefPubMedPubMedCentral
73.
Punnoose EA, Ferraldeschi R, Szafer-Glusman E, Tucker EK, Mohan S, Flohr P, et al. PTEN loss in circulating tumour cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients. Br J Cancer. 2015;113(8):1225–33.CrossRefPubMedPubMedCentral
74.
Antonarakis ES, Lu C, Luber B, Wang H, Chen Y, Nakazawa M, et al. Androgen receptor splice variant 7 and efficacy of taxane chemotherapy in patients with metastatic castration-resistant prostate cancer. JAMA Oncol. 2015;1(5):582–91.CrossRefPubMedPubMedCentral
75.
Scher HI, Lu D, Schreiber NA, Louw J, Graf RP, Vargas HA, et al. Association of AR-V7 on circulating tumor cells as a treatment-specific biomarker with outcomes and survival in castration-resistant prostate cancer. JAMA Oncol. 2016 Jun 4; doi:10.​1001/​jamaoncol.​2016.​1828.PubMed
76.
•• Beltran H, Jendrisak A, Landers M, Mosquera JM, Kossai M, Louw J, et al. The initial detection and partial characterization of circulating tumor cells in neuroendocrine prostate cancer. Clin Cancer Res. 2016;22(6):1510–9. Development of a NEPC CTC classifier based on low or absent AR expression, lower cytokeratin expression, and smaller cell morphology compared to typical CRPC CrossRefPubMed
77.
Romanel A, Gasi Tandefelt D, Conteduca V, Jayaram A, Casiraghi N, Wetterskog D, et al. Plasma AR and abiraterone-resistant prostate cancer. Sci Transl Med. 2015;7(312):312re10.CrossRefPubMed
78.
Carreira S, Romanel A, Goodall J, Grist E, Ferraldeschi R, Miranda S, et al. Tumor clone dynamics in lethal prostate cancer. Sci Transl Med. 2014;6(254):254ra125.CrossRefPubMedPubMedCentral
79.
Azad AA, Volik SV, Wyatt AW, Haegert A, Le Bihan S, Bell RH, et al. Androgen receptor gene aberrations in circulating cell-free DNA: biomarkers of therapeutic resistance in castration-resistant prostate cancer. Clin Cancer Res. 2015;21(10):2315–24.CrossRefPubMed
80.
Wyatt AW, Azad AA, Volik SV, Annala M, Beja K, McConeghy B, et al. Genomic alterations in cell-free DNA and enzalutamide resistance in castration-resistant prostate cancer. JAMA Oncol. 2016 May 5; doi:10.​1001/​jamaoncol.​2016.​0494.
81.
Xia Y, Huang CC, Dittmar R, Du M, Wang Y, Liu H, et al. Copy number variations in urine cell free DNA as biomarkers in advanced prostate cancer. Oncotarget. 2016;7(24):35818–31.PubMedPubMedCentral
82.
Motamedinia P, Scott AN, Bate KL, Sadeghi N, Salazar G, Shapiro E, et al. Urine exosomes for non-invasive assessment of gene expression and mutations of prostate cancer. PLoS One. 2016 May 4;11(5):e0154507.CrossRefPubMedPubMedCentral
83.
Minciacchi VR, You S, Spinelli C, Morley S, Zandian M, Aspuria PJ, et al. Large oncosomes contain distinct protein cargo and represent a separate functional class of tumor-derived extracellular vesicles. Oncotarget. 2015;6(13):11327–41.CrossRefPubMedPubMedCentral
84.
Meulenbeld HJ, Bleuse JP, Vinci EM, Raymond E, Vitali G, Santoro A, et al. Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure. BJU Int. 2013;111:44–52.CrossRefPubMed
85.
Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011;146(6):904–17.CrossRefPubMedPubMedCentral
86.
Asangani IA, Dommeti VL, Wang X, Malik R, Cieslik M, Yang R, et al. Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. Nature. 2014;510(7504):278–82.CrossRefPubMedPubMedCentral
87.
Bracken AP, Helin K. Polycomb group proteins: navigators of lineage pathways led astray in cancer. Nat Rev Cancer. 2009;9(11):773–84.CrossRefPubMed
88.
89.
Kleb B, Estécio MR, Zhang J, Tzelepi V, Chung W, Jelinek J, et al. Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas. Epigenetics. 2016;11(3):184–93.CrossRefPubMedPubMedCentral
90.
Saunders LR, Bankovich AJ, Anderson WC, Aujay MA, Bheddah S, Black K, et al. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Sci Transl Med. 2015;7(302):302ra136.CrossRefPubMedPubMedCentral
91.
Rudin CM, Pietanza MC, Bauer TM, Spigel DR, Ready N, Morgensztern D, et al. Safety and efficacy of single-agent rovalpituzumab tesirine (SC16LD6.5), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate (ADC) in recurrent or refractory small cell lung cancer (SCLC). J Clin Oncol. 2016;34 (suppl; abstr LBA8505).
92.
Ott PA, Elez Fernandez ME, Hiret S, Kim DW, Moss RA, Winser T, et al. Pembrolizumab (MK-3475) in patients (pts) with extensive-stage small cell lung cancer (SCLC): preliminary safety and efficacy results from KEYNOTE-028. J Clin Oncol. 2015;33 (suppl; abstr 7502).
93.
Antonia SJ, López-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016;17(7):883–95.CrossRefPubMed
94.
Graff JN, Alumkal JJ, Drake CG, Thomas GV, Redmond WL, Farhad M, et al. Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. Oncotarget. 2016; doi:10.​18632/​oncotarget.​10547.
95.
Geethakumari PR, Cookson MS, Kelly WK, Prostate Cancer Clinical Trials Working Group 3. The evolving biology of castration-resistant prostate cancer: review of recommendations from the prostate cancer clinical trials working group 3. Oncology (Williston Park). 2016;30(2):187–95. 199
Metadata
Title
Emerging Variants of Castration-Resistant Prostate Cancer
Authors
Panagiotis J. Vlachostergios
Loredana Puca
Himisha Beltran
Publication date
01-05-2017
Publisher
Springer US
Published in
Current Oncology Reports / Issue 5/2017
Print ISSN: 1523-3790
Electronic ISSN: 1534-6269
DOI
https://doi.org/10.1007/s11912-017-0593-6

Other articles of this Issue 5/2017

Current Oncology Reports 5/2017 Go to the issue

Breast Cancer (B Overmoyer, Section Editor)

The Evolving Role of the Estrogen Receptor Mutations in Endocrine Therapy-Resistant Breast Cancer

Gastrointestinal Cancers (J Meyer, Section Editor)

Immunotherapy for Esophageal Squamous Cell Carcinoma

Leukemia (A Aguayo, Section Editor)

Philadelphia-Like Acute Lymphoblastic Leukemia in Adults

Melanoma (RJ Sullivan, Section Editor)

Adjuvant Therapy for Melanoma

Lymphomas (MR Smith, Section Editor)

Optimal Therapy for Early-Stage Hodgkin’s Lymphoma: Risk Adapting, Response Adapting, and Role of Radiotherapy
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits