Literature DB >> 30301829

Expression of AR-V7 and ARv567es in Circulating Tumor Cells Correlates with Outcomes to Taxane Therapy in Men with Metastatic Prostate Cancer Treated in TAXYNERGY.

Scott T Tagawa1, Emmanuel S Antonarakis2, Ada Gjyrezi3, Giuseppe Galletti3, Seaho Kim3, Daniel Worroll3, John Stewart4, Atef Zaher4, Ted P Szatrowski5, Karla V Ballman3, Katsuhiro Kita3, Shinsuke Tasaki3, Yang Bai3, Luigi Portella3, Brian J Kirby3,6, Fred Saad7, Mario A Eisenberger2, David M Nanus3, Paraskevi Giannakakou1.   

Abstract

PURPOSE: Biomarkers aiding treatment optimization in metastatic castration-resistant prostate cancer (mCRPC) are scarce. The presence or absence of androgen receptor (AR) splice variants, AR-V7 and ARv567es, in mCRPC patient circulating tumor cells (CTC) may be associated with taxane treatment outcomes.Experimental Design: A novel digital droplet PCR (ddPCR) assay assessed AR-splice variant expression in CTCs from patients receiving docetaxel or cabazitaxel in TAXYNERGY (NCT01718353). Patient outcomes were examined according to AR-splice variant expression, including prostate-specific antigen (PSA)50 response and progression-free survival (PFS).
RESULTS: Of the 54 evaluable patients, 36 (67%) were AR-V7+, 42 (78%) were ARv567es+, 29 (54%) were double positive, and 5 (9%) were double negative. PSA50 response rates at any time were numerically higher for AR-V7- versus AR-V7+ (78% vs. 58%; P = 0.23) and for ARv567es- versus ARv567es+ (92% vs. 57%; P = 0.04) patients. When AR-V mRNA status was correlated with change in nuclear AR from cycle 1 day 1 to day 8 (n = 24), AR-V7+ patients (n = 16) had a 0.4% decrease versus a 12.9% and 26.7% decrease in AR-V7-/ARv567es- (n = 3) and AR-V7-/ARv567es+ (n = 5) patients, respectively, suggesting a dominant role for AR-V7 over ARv567es. Median PFS was 12.02 versus 8.48 months for AR-V7- versus AR-V7+ (HR = 0.38; P = 0.01), and 12.71 versus 7.29 months for ARv567es- versus ARv567es+ (HR = 0.37; P = 0.02). For AR-V7+, AR-V7-/ARv567es+, and AR-V7-/ARv567es- patients, median PFS was 8.48, 11.17, and 16.62 months, respectively (P = 0.0013 for trend).
CONCLUSIONS: Although detection of both CTC-specific AR-V7 and ARv567es by ddPCR influenced taxane outcomes, AR-V7 primarily mediated the prognostic impact. The absence of both variants was associated with the best response and PFS with taxane treatment.See related commentary by Dehm et al., p. 1696. ©2018 American Association for Cancer Research.

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Year:  2018        PMID： 30301829      PMCID： PMC6432911          DOI： 10.1158/1078-0432.CCR-18-0320

Source DB:  PubMed          Journal:  Clin Cancer Res        ISSN： 1078-0432            Impact factor:   12.531


  41 in total

1.  Commentary on "Integrative clinical genomics of advanced prostate cancer". Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, Montgomery B, Taplin ME, Pritchard CC, Attard G, Beltran H, Abida W, Bradley RK, Vinson J, Cao X, Vats P, Kunju LP, Hussain M, Feng FY, Tomlins SA, Cooney KA, Smith DC, Brennan C, Siddiqui J, Mehra R, Chen Y, Rathkopf DE, Morris MJ, Solomon SB, Durack JC, Reuter VE, Gopalan A, Gao J, Loda M, Lis RT, Bowden M, Balk SP, Gaviola G, Sougnez C, Gupta M, Yu EY, Mostaghel EA, Cheng HH, Mulcahy H, True LD, Plymate SR, Dvinge H, Ferraldeschi R, Flohr P, Miranda S, Zafeiriou Z, Tunariu N, Mateo J, Perez-Lopez R, Demichelis F, Robinson BD, Schiffman M, Nanus DM, Tagawa ST, Sigaras A, Eng KW, Elemento O, Sboner A, Heath EI, Scher HI, Pienta KJ, Kantoff P, de Bono JS, Rubin MA, Nelson PS, Garraway LA, Sawyers CL, Chinnaiyan AM.Cell. 21 May 2015;161(5):1215-1228.

Authors:  Stephen J Freedland; William J Aronson
Journal:  Urol Oncol       Date:  2017-06-13       Impact factor: 3.498

2.  An RNA-Based Digital Circulating Tumor Cell Signature Is Predictive of Drug Response and Early Dissemination in Prostate Cancer.

Authors:  David T Miyamoto; Richard J Lee; Mark Kalinich; Joseph A LiCausi; Yu Zheng; Tianqi Chen; John D Milner; Erin Emmons; Uyen Ho; Katherine Broderick; Erin Silva; Sarah Javaid; Tanya Todorova Kwan; Xin Hong; Douglas M Dahl; Francis J McGovern; Jason A Efstathiou; Matthew R Smith; Lecia V Sequist; Ravi Kapur; Chin-Lee Wu; Shannon L Stott; David T Ting; Anita Giobbie-Hurder; Mehmet Toner; Shyamala Maheswaran; Daniel A Haber
Journal:  Cancer Discov       Date:  2018-01-04       Impact factor: 39.397

3.  Digital droplet PCR (ddPCR) for the precise quantification of human T-lymphotropic virus 1 proviral loads in peripheral blood and cerebrospinal fluid of HAM/TSP patients and identification of viral mutations.

Authors:  Giovanna S Brunetto; Raya Massoud; Emily C Leibovitch; Breanna Caruso; Kory Johnson; Joan Ohayon; Kaylan Fenton; Irene Cortese; Steven Jacobson
Journal:  J Neurovirol       Date:  2014-04-30       Impact factor: 2.643

4.  Taxane-induced blockade to nuclear accumulation of the androgen receptor predicts clinical responses in metastatic prostate cancer.

Authors:  Medha S Darshan; Matthew S Loftus; Maria Thadani-Mulero; Benjamin P Levy; Daniel Escuin; Xi Kathy Zhou; Ada Gjyrezi; Chantal Chanel-Vos; Ruoqian Shen; Scott T Tagawa; Neil H Bander; David M Nanus; Paraskevi Giannakakou
Journal:  Cancer Res       Date:  2011-07-28       Impact factor: 12.701

5.  Androgen receptor splice variants determine taxane sensitivity in prostate cancer.

Authors:  Maria Thadani-Mulero; Luigi Portella; Shihua Sun; Matthew Sung; Alexandre Matov; Robert L Vessella; Eva Corey; David M Nanus; Stephen R Plymate; Paraskevi Giannakakou
Journal:  Cancer Res       Date:  2014-02-20       Impact factor: 12.701

6.  A Whole Blood Assay for AR-V7 and ARv567es in Patients with Prostate Cancer.

Authors:  Xichun Liu; Elisa Ledet; Dongying Li; Ary Dotiwala; Allie Steinberger; Allison Feibus; Jianzhuo Li; Yanfeng Qi; Jonathan Silberstein; Benjamin Lee; Yan Dong; Oliver Sartor; Haitao Zhang
Journal:  J Urol       Date:  2016-07-20       Impact factor: 7.450

7.  Optimal sequencing of docetaxel and abiraterone in men with metastatic castration-resistant prostate cancer.

Authors:  Benjamin L Maughan; Xian C Xhou; Daniel L Suzman; Rosa Nadal; Sunakshi Bassi; Michael T Schweizer; Emmanuel S Antonarakis
Journal:  Prostate       Date:  2015-08-26       Impact factor: 4.104

8.  Development and evaluation of a real-time PCR assay for detection of Pneumocystis jirovecii DNA in bronchoalveolar lavage fluid of HIV-infected patients.

Authors:  J F Huggett; M S Taylor; G Kocjan; H E Evans; S Morris-Jones; V Gant; T Novak; A M Costello; A Zumla; R F Miller
Journal:  Thorax       Date:  2007-08-10       Impact factor: 9.139

9.  Reverse transcriptase droplet digital PCR shows high resilience to PCR inhibitors from plant, soil and water samples.

Authors:  Nejc Rački; Tanja Dreo; Ion Gutierrez-Aguirre; Andrej Blejec; Maja Ravnikar
Journal:  Plant Methods       Date:  2014-12-31       Impact factor: 4.993

Review 10.  Splice Variants of Androgen Receptor and Prostate Cancer.

Authors:  Orazio Caffo; Francesca Maines; Antonello Veccia; Stefania Kinspergher; Enzo Galligioni
Journal:  Oncol Rev       Date:  2016-05-30
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  36 in total

Review 1.  Cellular and Molecular Mechanisms Underlying Prostate Cancer Development: Therapeutic Implications.

Authors:  Ugo Testa; Germana Castelli; Elvira Pelosi
Journal:  Medicines (Basel)       Date:  2019-07-30

2.  Considerations for AR-V7 testing in clinical routine practice.

Authors:  Christof Bernemann; Laura-Maria Krabbe; Andres Jan Schrader
Journal:  Ann Transl Med       Date:  2019-12

3.  Current status of circulating tumor cell androgen receptor splice variant-7 in metastatic castration-resistant prostate cancer.

Authors:  Shinichi Sakamoto
Journal:  Ann Transl Med       Date:  2019-12

4.  Resistance Mechanisms to Taxanes and PARP Inhibitors in Advanced Prostate Cancer.

Authors:  Alan P Lombard; Allen C Gao
Journal:  Curr Opin Endocr Metab Res       Date:  2020-02-19

Review 5.  Current and Emerging Applications of Droplet Digital PCR in Oncology: An Updated Review.

Authors:  Susana Olmedillas-López; Rocío Olivera-Salazar; Mariano García-Arranz; Damián García-Olmo
Journal:  Mol Diagn Ther       Date:  2021-11-13       Impact factor: 4.074

6.  Androgen receptor variant-driven prostate cancer II: advances in clinical investigation.

Authors:  Emmanuel S Antonarakis; Jun Luo; Andrew J Armstrong; Landon C Brown; Changxue Lu
Journal:  Prostate Cancer Prostatic Dis       Date:  2020-02-24       Impact factor: 5.554

7.  Androgen receptor splice variant 7 (AR-V7) and AR full-length (AR-FL) as predictive biomarkers of therapeutic resistance: partners in crime?

Authors:  Roberto H Barbier; Cindy H Chau; William D Figg
Journal:  BJU Int       Date:  2019-09-20       Impact factor: 5.588

8.  Androgen receptor variants: RNA-based mechanisms and therapeutic targets.

Authors:  Kiel T Tietz; Scott M Dehm
Journal:  Hum Mol Genet       Date:  2020-09-30       Impact factor: 6.150

Review 9.  Dissecting the Hormonal Signaling Landscape in Castration-Resistant Prostate Cancer.

Authors:  Fabrizio Fontana; Patrizia Limonta
Journal:  Cells       Date:  2021-05-07       Impact factor: 6.600

10.  Androgen receptor variant shows heterogeneous expression in prostate cancer according to differentiation stage.

Authors:  Ada Gjyrezi; Giuseppe Galletti; Jiaren Zhang; Daniel Worroll; Michael Sigouros; Seaho Kim; Victoria Cooley; Karla V Ballman; Allyson J Ocean; Manish A Shah; Joseph M Scandura; Andrea Sboner; David M Nanus; Himisha Beltran; Scott Tagawa; Paraskevi Giannakakou
Journal:  Commun Biol       Date:  2021-06-24
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