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53. A Multicohort Open-label Phase II Trial of Bipolar Androgen Therapy in Men with Metastatic Castration-resistant Prostate Cancer (RESTORE): A Comparison of Post-abiraterone Versus Post-enzalutamide Cohorts

Author

Markowski, Mark C., Wang, Hao, Sullivan, Rana, Rifkind, Irina, Sinibaldi, Victoria, Schweizer, Michael T., Teply, Benjamin A., Ngomba, Nduku, Fu, Wei, Carducci, Michael A., Paller, Channing J., Marshall, Catherine H., Eisenberger, Mario A., Luo, Jun, Antonarakis, Emmanuel S., and Denmeade, Samuel R.

Published
2021
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54. Association between BRCA2 alterations and intraductal and cribriform histologies in prostate cancer

Author

Lozano, Rebeca, Salles, Daniela C., Sandhu, Shahneen, Aragón, Isabel M., Thorne, Heather, López-Campos, Fernando, Rubio-Briones, José, Gutierrez-Pecharroman, Ana M., Maldonado, Laneisha, di Domenico, Tomas, Sanz, Alejandro, Prieto, Juan D., García, Isabel, Pacheco, María I., Garcés, Teresa, Llacer, Casilda, Romero-Laorden, Nuria, Zambrana, Francisco, López-Casas, Pedro P., Lorente, David, Mateo, Joaquin, Pritchard, Colin C., Antonarakis, Emmanuel S., Olmos, David, Lotan, Tamara L., and Castro, Elena

Published
2021
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55. Pan-Cancer Analysis of Copy-Number Features Identifies Recurrent Signatures and a Homologous Recombination Deficiency Biomarker to Predict Poly (ADP-Ribose) Polymerase Inhibitor Response

Author

Moore, Jay A., Chen, Kuei-Ting, Madison, Russell, Newberg, Justin Y., Fleischmann, Zoe, Wang, Shuoguo, Sharaf, Radwa, Murugesan, Karthikeyan, Fendler, Bernard J., Hughes, Jason, Schrock, Alexa B., Hegde, Priti S., Oxnard, Geoffrey R., Fabrizio, David, Frampton, Garrett M., Antonarakis, Emmanuel S., Sokol, Ethan S., and Jin, Dexter X.

Published
2023
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56. MLH1 Loss in Primary Prostate Cancer

Author

Nourmohammadi Abadchi, Sanaz, Sena, Laura A., Antonarakis, Emmanuel S., Pritchard, Colin C., Eshleman, James R., Konnick, Eric Q., Salipante, Stephen J., Shenderov, Eugene, and Lotan, Tamara L.

Published
2023
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58. Senescence Reprogramming by TIMP1 Deficiency Promotes Prostate Cancer Metastasis

Author

Guccini, Ilaria, Revandkar, Ajinkya, D'Ambrosio, Mariantonietta, Colucci, Manuel, Pasquini, Emiliano, Mosole, Simone, Troiani, Martina, Brina, Daniela, Sheibani-Tezerji, Raheleh, Elia, Angela Rita, Rinaldi, Andrea, Pernigoni, Nicolò, Rüschoff, Jan Hendrik, Dettwiler, Susanne, De Marzo, Angelo M., Antonarakis, Emmanuel S., Borrelli, Costanza, Moor, Andreas E., Garcia-Escudero, Ramon, Alajati, Abdullah, Attanasio, Giuseppe, Losa, Marco, Moch, Holger, Wild, Peter, Egger, Gerda, and Alimonti, Andrea

Published
2021
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59. Genomic, immunologic, and prognostic associations of TROP2 (TACSTD2) expression in solid tumors.

Author

Morgenstern-Kaplan, Dan, Kareff, Samuel A, Trabolsi, Asaad, Rodriguez, Estelamari, Krause, Harris, Ribeiro, Jennifer R, Tan, Heng, Antonarakis, Emmanuel S, Lou, Emil, Nagasaka, Misako, Algaze, Sandra, Lenz, Heinz-Josef, Liu, Stephen V, Halmos, Balazs, Hoon, Dave S B, Seeber, Andreas, Ma, Patrick C, El-Deiry, Wafik S, Vanderwalde, Ari M, and Lopes, Gilberto

Subjects
PROTEINS, GENOMICS, RESEARCH funding, BREAST tumors, FISHER exact test, DNA, COLORECTAL cancer, DESCRIPTIVE statistics, MANN Whitney U Test, CHI-squared test, GENE expression, IMMUNOHISTOCHEMISTRY, KAPLAN-Meier estimator, PANCREATIC tumors, GENES, GENE expression profiling, TUMORS, TUMOR antigens, GENETIC mutation, SEQUENCE analysis, OVERALL survival, HEPATOCELLULAR carcinoma, CYCLIN-dependent kinases
Abstract

Background TROP2 (TACSTD2) expression is associated with decreased overall survival (OS) in some solid tumors, and the TROP2-targeting antibody-drug conjugate (ADC) sacituzumab govitecan has been approved in breast and urothelial carcinomas. We aimed to explore the multi-omic landscape associated with TACSTD2 gene expression in various solid tumors to identify patients most likely to benefit from this approach. Methods Breast (N  = 11 246), colorectal (N  = 15 425), hepatocellular (N  = 433), pancreatic (N  = 5488), and urothelial (N  = 4125) tumors were stratified into quartiles by TACSTD2 gene expression, analyzed by next-generation DNA sequencing, whole transcriptome sequencing, and immunohistochemistry at Caris Life Sciences (Phoenix, AZ). Survival data were obtained from insurance claims, and Kaplan-Meier estimates were calculated for molecularly defined cohorts. Results Several pathogenic mutations were associated with TACSTD2 -high tumors, including TP53 in breast, colorectal (CRC), pancreatic, and hepatocellular cancers; KRAS in pancreatic and CRC cancers; ARID1A and FGFR3 in urothelial cancer; and CTNNB1 in hepatocellular cancer. TACSTD2-low breast tumors were enriched for copy number amplifications in CCND1 and FGF/R family member genes. TACSTD2 high was generally associated with more immune cell infiltration and greater T-cell inflammation scores. Patients with TACSTD2 -high breast, CRC, and pancreatic cancers demonstrated a significantly shorter OS than TACSTD2 -low tumors. This was restricted to CRC with microsatellite stable tumors and patients with pancreatic cancer with KRAS -mutant tumors. Patients with breast cancer with TACSTD2 -high tumors also experienced significantly worse OS following immune checkpoint inhibitors. Conclusions TACSTD2 expression is associated with key driver alterations and a more active immune microenvironment, suggesting possible combinatorial strategies with TROP2-targeting ADCs plus immunotherapy in various solid tumors. [ABSTRACT FROM AUTHOR]

Published
2024
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60. Current uses and resistance mechanisms of enzalutamide in prostate cancer treatment.

Author

Miller, Carly D., Likasitwatanakul, Pornlada, Toye, Eamon, Hwang, Justin H., and Antonarakis, Emmanuel S.

Subjects
ANDROGEN receptors, CASTRATION-resistant prostate cancer, PROSTATE cancer, CANCER treatment, POLY(ADP-ribose) polymerase, TUMORS, METASTASIS
Abstract

Introduction: Prostate cancer continues to be a major cause of morbidity and mortality for men worldwide. Enzalutamide, a second-generation non-steroidal antiandrogen that blocks androgen receptor (AR) transcriptional activity, is a treatment for biochemically recurrent, metastatic, castration-sensitive, and castration-resistant tumors. Unfortunately, most patients ultimately develop resistance to enzalutamide, making long-term treatment with this agent challenging. Areas covered: We performed a literature search of PubMed without date restrictions to investigate the literature surrounding enzalutamide and discuss the current uses of enzalutamide, proposed mechanisms driving resistance, and summarize current efforts to mitigate this resistance. Expert opinion: Enzalutamide is an effective prostate cancer therapy that is currently used in biochemically recurrent and metastatic disease and for both castration-sensitive and castration-resistant tumors. Unfortunately, resistance to enzalutamide occurs in each of these scenarios. In the clinical setting, enzalutamide-resistant tumors are either AR-driven or AR-indifferent. AR-dependent resistance mechanisms include genomic or epigenomic events that result in enhanced AR signaling. Tumors that do not require AR signaling instead may depend on alternative oncogenic pathways. There are numerous strategies to mitigate enzalutamide resistance, including concurrent use of PARP inhibitors or immune therapies. Additional work is required to uncover novel approaches to treat patients in the enzalutamide-resistant setting. [ABSTRACT FROM AUTHOR]

Published
2024
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61. Olaparib Without Androgen Deprivation for High-Risk Biochemically Recurrent Prostate Cancer Following Prostatectomy: A Nonrandomized Controlled Trial.

Author

Marshall, Catherine H., Teply, Benjamin A., Lu, Jiayun, Oliveira, Lia, Wang, Hao, Mao, Shifeng S., Kelly, W. Kevin, Paller, Channing J., Markowski, Mark C., Denmeade, Samuel R., King, Serina, Sullivan, Rana, Davicioni, Elai, Proudfoot, James A., Eisenberger, Mario A., Carducci, Michael A., Lotan, Tamara L., and Antonarakis, Emmanuel S.

Published
2024
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62. TRIUMPH: phase II trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer harboring germline homologous recombination repair gene mutations.

Author

Markowski, Mark C, Sternberg, Cora N, Wang, Hao, Wang, Tingchang, Linville, Laura, Marshall, Catherine H, Sullivan, Rana, King, Serina, Lotan, Tamara L, and Antonarakis, Emmanuel S

Subjects
THERAPEUTIC use of antineoplastic agents, RESEARCH funding, ENZYME inhibitors, CLINICAL trials, PROSTATE tumors, TREATMENT effectiveness, DESCRIPTIVE statistics, TUMOR markers, METASTASIS, INDOLE compounds, DNA repair, RESEARCH, GENETIC mutation, SURVIVAL analysis (Biometry), CONFIDENCE intervals, SEQUENCE analysis
Abstract

Background The activity of PARP inhibitors (PARPi) in patients with homologous recombination repair (HRR) mutations and metastatic castration-resistant prostate cancer has been established. We hypothesized that the benefit of PARPi can be maintained in the absence of androgen deprivation therapy (ADT) in an HRR-mutated population. We report the results of a phase II clinical trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Methods This was a multi-center, single-arm phase II trial (NCT03413995) for patients with asymptomatic, mHSPC. Patients were required to have a pathogenic germline mutation in an HRR gene for eligibility. All patients received rucaparib 600 mg by mouth twice daily, without androgen deprivation. The primary endpoint was a confirmed PSA50 response rate. Results Twelve patients were enrolled, 7 with a BRCA1/2 mutation and 5 with a CHEK2 mutation. The confirmed PSA50 response rate to rucaparib was 41.7% (N = 5/12, 95% CI: 15.2-72.3%, one-sided P  = .81 against the 50% null), which did not meet the pre-specified efficacy boundary to enroll additional patients. In patients with measurable disease, the objective response rate was 60% (N = 3/5), all with a BRCA2 mutation. The median radiographic progression-free survival on rucaparib was estimated at 12.0 months (95% CI: 8.0-NR months). The majority of adverse events were grade ≤2, and expected. Conclusion Rucaparib can induce clinical responses in a biomarker-selected metastatic prostate cancer population without concurrent ADT. However, the pre-specified efficacy threshold was not met, and enrolment was truncated. Although durable responses were observed in a subset of patients, further study of PARPi treatment without ADT in mHSPC is unlikely to change clinical practice. [ABSTRACT FROM AUTHOR]

Published
2024
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64. Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12 Alterations in the Phase 2 IMPACT Trial

Author

Nguyen, Charles B., primary, Reimers, Melissa A., additional, Perera, Chamila, additional, Abida, Wassim, additional, Chou, Jonathan, additional, Feng, Felix Y., additional, Antonarakis, Emmanuel S., additional, McKay, Rana R., additional, Pachynski, Russell K., additional, Zhang, Jingsong, additional, Reichert, Zachery R., additional, Palmbos, Phillip L., additional, Caram, Megan E.V., additional, Vaishampayan, Ulka N., additional, Heath, Elisabeth I., additional, Hopkins, Alexander C., additional, Cieslik, Marcin P., additional, Wu, Yi-Mi, additional, Robinson, Dan, additional, Baladandayuthapani, Veerabhadran, additional, Chinnaiyan, Arul M., additional, and Alva, Ajjai S., additional

Published
2024
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67. Expert Perspectives on Controversies in Castration-Sensitive Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 1

Author

Crawford, E. David, primary, Bryce, Alan H., additional, Hussain, Maha H., additional, Agarwal, Neeraj, additional, Beltran, Himisha, additional, Cooperberg, Matthew R., additional, Petrylak, Daniel P., additional, Shore, Neal, additional, Spratt, Daniel E., additional, Tagawa, Scott T., additional, Antonarakis, Emmanuel S., additional, Aparicio, Ana M., additional, Armstrong, Andrew J., additional, Boike, Thomas P., additional, Calais, Jeremie, additional, Carducci, Michael A., additional, Chapin, Brian F., additional, Cookson, Michael S., additional, Davis, John W., additional, Dorff, Tanya, additional, Eggener, Scott E., additional, Feng, Felix Y., additional, Gleave, Martin, additional, Higano, Celestia, additional, Iagaru, Andrei, additional, Morgans, Alicia K., additional, Morris, Michael, additional, Murray, Katie S., additional, Poage, Wendy, additional, Rettig, Matthew B., additional, Sartor, Oliver, additional, Scher, Howard I., additional, Sieber, Paul, additional, Small, Eric, additional, Srinivas, Sandy, additional, Yu, Evan Y., additional, Zhang, Tian, additional, and Koo, Phillip J., additional

Published
2024
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68. Expert Perspectives on Controversies in Metastatic Castration-Resistant Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 2

Author

Bryce, Alan H., primary, Crawford, E. David, additional, Agarwal, Neeraj, additional, Hussain, Maha H., additional, Beltran, Himisha, additional, Cooperberg, Matthew R., additional, Petrylak, Daniel P., additional, Shore, Neal, additional, Spratt, Daniel E., additional, Tagawa, Scott T., additional, Antonarakis, Emmanuel S., additional, Aparicio, Ana M., additional, Armstrong, Andrew J., additional, Boike, Thomas P., additional, Calais, Jeremie, additional, Carducci, Michael A., additional, Chapin, Brian F., additional, Cookson, Michael S., additional, Davis, John W., additional, Dorff, Tanya, additional, Eggener, Scott E., additional, Feng, Felix Y., additional, Gleave, Martin, additional, Higano, Celestia, additional, Iagaru, Andrei, additional, Morgans, Alicia K., additional, Morris, Michael, additional, Murray, Katie S., additional, Poage, Wendy, additional, Rettig, Matthew B., additional, Sartor, Oliver, additional, Scher, Howard I., additional, Sieber, Paul, additional, Small, Eric, additional, Srinivas, Sandy, additional, Yu, Evan Y., additional, Zhang, Tian, additional, and Koo, Phillip J., additional

Published
2024
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69. Characterization and impact of non‐canonical WNT signaling on outcomes of urothelial carcinoma

Author

Meagher, Margaret, primary, Krause, Harris, additional, Elliott, Andrew, additional, Farrell, Alex, additional, Antonarakis, Emmanuel S., additional, Bastos, Bruno, additional, Heath, Elisabeth I., additional, Jamieson, Christina, additional, Stewart, Tyler F., additional, Bagrodia, Aditya, additional, Nabhan, Chadi, additional, Oberley, Matt, additional, McKay, Rana R., additional, and Salmasi, Amirali, additional

Published
2024
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70. Supplementary Figure S1 from The Impact of Circulating Tumor Cell HOXB13 RNA Detection in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide

Author

Halabi, Susan, primary, Guo, Siyuan, primary, Park, Joseph J., primary, Nanus, David M., primary, George, Daniel J., primary, Antonarakis, Emmanuel S., primary, Danila, Daniel Costin, primary, Szmulewitz, Russell Zelig, primary, McDonnell, Donald P., primary, Norris, John D., primary, Lu, Changxue, primary, Luo, Jun, primary, and Armstrong, Andrew J., primary

Published
2024
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71. Supplementary Table S4 from The Impact of Circulating Tumor Cell HOXB13 RNA Detection in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide

Author

Halabi, Susan, primary, Guo, Siyuan, primary, Park, Joseph J., primary, Nanus, David M., primary, George, Daniel J., primary, Antonarakis, Emmanuel S., primary, Danila, Daniel Costin, primary, Szmulewitz, Russell Zelig, primary, McDonnell, Donald P., primary, Norris, John D., primary, Lu, Changxue, primary, Luo, Jun, primary, and Armstrong, Andrew J., primary

Published
2024
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72. Androgen receptor activity in prostate cancer dictates efficacy of bipolar androgen therapy through MYC

Author

Sena, Laura A., Kumar, Rajendra, Sanin, David E., Thompson, Elizabeth A., Rosen, D. Marc, Dalrymple, Susan L., Antony, Lizamma, Yang, Yuhan, Gomes-Alexandre, Carolina, Hicks, Jessica L., Jones, Tracy, Bowers, Kiara A., Eskra, Jillian N., Meyers, Jennifer, Gupta, Anuj, Skaist, Alyza, Yegnasubramanian, Srinivasan, Luo, Jun, Brennen, W. Nathaniel, Kachhap, Sushant K., Antonarakis, Emmanuel S., De Marzo, Angelo M., Isaacs, John T., Markowski, Mark C., and Denmeade, Samuel R.

Subjects
Care and treatment, Physiological aspects, Genetic aspects, Research, Methods, Health aspects, Androgen receptors -- Health aspects -- Physiological aspects, Cancer research, Proto-oncogenes -- Health aspects -- Physiological aspects, Prostate cancer -- Care and treatment -- Genetic aspects, Gene expression -- Research, Hormone therapy -- Methods, Oncology, Experimental, Cancer -- Research
Abstract

Introduction Signaling through the androgen receptor (AR) is the primary oncogenic driver of prostate adenocarcinoma. Inhibition of AR signaling by androgen deprivation and AR inhibitors produces significant therapeutic and palliative [...], Testosterone is the canonical growth factor of prostate cancer but can paradoxically suppress its growth when present at supraphysiological levels. We have previously demonstrated that the cyclical administration of supraphysiological androgen (SPA), termed bipolar androgen therapy (BAT), can result in tumor regression and clinical benefit for patients with castrationresistant prostate cancer. However, predictors and mechanisms of response and resistance have been ill defined. Here, we show that growth inhibition of prostate cancer models by SPA required high androgen receptor (AR) activity and were driven in part by downregulation of MYC. Using matched sequential patient biopsies, we show that high pretreatment AR activity predicted downregulation of MYC, improved clinical response, and prolonged progression-free and overall survival for patients on BAT. BAT induced strong downregulation of AR in all patients, which is shown to be a primary mechanism of acquired resistance to SPA. Acquired resistance was overcome by alternating SPA with the AR inhibitor enzalutamide, which induced adaptive upregulation of AR and resensitized prostate cancer to SPA. This work identifies high AR activity as a predictive biomarker of response to BAT and supports a treatment paradigm for prostate cancer involving alternating between AR inhibition and activation.

Published
2022
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76. Management of patients with advanced prostate cancer. Report from the 2024 advanced prostate cancer consensus conference (APCCC)

Author

Gillessen, Silke, Turco, Fabio, Davis, Ian D., Efstathiou, Jason A., Fizazi, Karim, James, Nicholas D., Shore, Neal, Small, Eric, Smith, Matthew, Sweeney, Christopher J., Tombal, Bertrand, Zilli, Thomas, Agarwal, Neeraj, Antonarakis, Emmanuel S., Aparicio, Ana, Armstrong, Andrew J., Bastos, Diogo Assed, Attard, Gerhardt, Axcrona, Karol, Ayadi, Mouna, Beltran, Himisha, Bjartell, Anders, Blanchard, Pierre, Bourlon, Maria T., Briganti, Alberto, Bulbul, Muhammad, Buttigliero, Consuelo, Caffo, Orazio, Castellano, Daniel, Castro, Elena, Cheng, Heather H., Chi, Kim N., Clarke, Caroline S., Clarke, Noel, de Bono, Johann S., De Santis, Maria, Duran, Ignacio, Efstathiou, Eleni, Ekeke, Onyeanunam N., El Nahas, Tamer I.H., Emmett, Louise, Fanti, Stefano, Fatiregun, Omolara A., Feng, Felix Y., Fong, Peter C.C., Fonteyne, Valerie, Fossati, Nicola, George, Daniel J., Gleave, Martin E., Gravis, Gwenaelle, Halabi, Susan, Heinrich, Daniel, Herrmann, Ken, Hofman, Michael S., Hope, Thomas A., Horvath, Lisa G., Hussain, Maha H.A., Jereczek-Fossa, Barbara Alicja, Jones, Robert J., Joshua, Anthony M., Kanesvaran, Ravindren, Keizman, Daniel, Khauli, Raja B., Kramer, Gero, Loeb, Stacy, Mahal, Brandon A., Maluf, Fernando C., Mateo, Joaquin, Matheson, David, Matikainen, Mika P., McDermott, Ray, McKay, Rana R., Mehra, Niven, Merseburger, Axel S., Morgans, Alicia K., Morris, Michael J., Mrabti, Hind, Mukherji, Deborah, Murphy, Declan G., Murthy, Vedang, Mutambirwa, Shingai B.A., Nguyen, Paul L., Oh, William K., Ost, Piet, O'Sullivan, Joe M., Padhani, Anwar R., Parker, Chris, Poon, Darren M.C., Pritchard, Colin C., Rabah, Danny M, Rathkopf, Dana, Reiter, Robert E., Renard-Penna, Raphaele, Ryan, Charles J., Saad, Fred, Sade, Juan Pablo, Sandhu, Shahneen, Sartor, Oliver A., Schaeffer, Edward, Scher, Howard I., Sharifi, Nima, Skoneczna, Iwona A., Soule, Howard R., Spratt, Daniel E., Srinivas, Sandy, Sternberg, Cora N., Suzuki, Hiroyoshi, Taplin, Mary-Ellen, Thellenberg-Karlsson, Camilla, Tilki, Derya, Türkeri, Levent N., Uemura, Hiroji, Ürün, Yüksel, Vale, Claire L., Vapiwala, Neha, Walz, Jochen, Yamoah, Kosj, Ye, Dingwei, Yu, Evan Y., Zapatero, Almudena, Omlin, Aurelius, Gillessen, Silke, Turco, Fabio, Davis, Ian D., Efstathiou, Jason A., Fizazi, Karim, James, Nicholas D., Shore, Neal, Small, Eric, Smith, Matthew, Sweeney, Christopher J., Tombal, Bertrand, Zilli, Thomas, Agarwal, Neeraj, Antonarakis, Emmanuel S., Aparicio, Ana, Armstrong, Andrew J., Bastos, Diogo Assed, Attard, Gerhardt, Axcrona, Karol, Ayadi, Mouna, Beltran, Himisha, Bjartell, Anders, Blanchard, Pierre, Bourlon, Maria T., Briganti, Alberto, Bulbul, Muhammad, Buttigliero, Consuelo, Caffo, Orazio, Castellano, Daniel, Castro, Elena, Cheng, Heather H., Chi, Kim N., Clarke, Caroline S., Clarke, Noel, de Bono, Johann S., De Santis, Maria, Duran, Ignacio, Efstathiou, Eleni, Ekeke, Onyeanunam N., El Nahas, Tamer I.H., Emmett, Louise, Fanti, Stefano, Fatiregun, Omolara A., Feng, Felix Y., Fong, Peter C.C., Fonteyne, Valerie, Fossati, Nicola, George, Daniel J., Gleave, Martin E., Gravis, Gwenaelle, Halabi, Susan, Heinrich, Daniel, Herrmann, Ken, Hofman, Michael S., Hope, Thomas A., Horvath, Lisa G., Hussain, Maha H.A., Jereczek-Fossa, Barbara Alicja, Jones, Robert J., Joshua, Anthony M., Kanesvaran, Ravindren, Keizman, Daniel, Khauli, Raja B., Kramer, Gero, Loeb, Stacy, Mahal, Brandon A., Maluf, Fernando C., Mateo, Joaquin, Matheson, David, Matikainen, Mika P., McDermott, Ray, McKay, Rana R., Mehra, Niven, Merseburger, Axel S., Morgans, Alicia K., Morris, Michael J., Mrabti, Hind, Mukherji, Deborah, Murphy, Declan G., Murthy, Vedang, Mutambirwa, Shingai B.A., Nguyen, Paul L., Oh, William K., Ost, Piet, O'Sullivan, Joe M., Padhani, Anwar R., Parker, Chris, Poon, Darren M.C., Pritchard, Colin C., Rabah, Danny M, Rathkopf, Dana, Reiter, Robert E., Renard-Penna, Raphaele, Ryan, Charles J., Saad, Fred, Sade, Juan Pablo, Sandhu, Shahneen, Sartor, Oliver A., Schaeffer, Edward, Scher, Howard I., Sharifi, Nima, Skoneczna, Iwona A., Soule, Howard R., Spratt, Daniel E., Srinivas, Sandy, Sternberg, Cora N., Suzuki, Hiroyoshi, Taplin, Mary-Ellen, Thellenberg-Karlsson, Camilla, Tilki, Derya, Türkeri, Levent N., Uemura, Hiroji, Ürün, Yüksel, Vale, Claire L., Vapiwala, Neha, Walz, Jochen, Yamoah, Kosj, Ye, Dingwei, Yu, Evan Y., Zapatero, Almudena, and Omlin, Aurelius

Abstract

Background and objective: Innovations have improved outcomes in advanced prostate cancer (PC). Nonetheless, we continue to lack high-level evidence on a variety of topics that greatly impact daily practice. The 2024 Advanced Prostate Cancer Consensus Conference (APCCC) surveyed experts on key questions in clinical management in order to supplement evidence-based guidelines. Here we present voting results for questions from APCCC 2024. Methods: Before the conference, a panel of 120 international PC experts used a modified Delphi process to develop 183 multiple-choice consensus questions on eight different topics. Before the conference, these questions were administered via a web-based survey to the voting panel members (“panellists”). Key findings and limitations: Consensus was a priori defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. The voting results show varying degrees of consensus, as discussed in this article and detailed in the Supplementary material. These findings do not include a formal literature review or meta-analysis. Conclusions and clinical implications: The voting results can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers in prioritising areas for future research. Diagnostic and treatment decisions should always be individualised on the basis of patient and cancer characteristics, and should incorporate current and emerging clinical evidence, guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2024 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials.

Published
2024
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78. A MYC and RAS co-activation signature in localized prostate cancer drives bone metastasis and castration resistance

Author

Arriaga, Juan M., Panja, Sukanya, Alshalalfa, Mohammed, Zhao, Junfei, Zou, Min, Giacobbe, Arianna, Madubata, Chioma J., Kim, Jaime Yeji, Rodriguez, Antonio, Coleman, Ilsa, Virk, Renu K., Hibshoosh, Hanina, Ertunc, Onur, Ozbek, Büşra, Fountain, Julia, Jeffrey Karnes, R., Luo, Jun, Antonarakis, Emmanuel S., Nelson, Peter S., Feng, Felix Y., Rubin, Mark A., De Marzo, Angelo M., Rabadan, Raul, Sims, Peter A., Mitrofanova, Antonina, and Abate-Shen, Cory

Published
2020
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88. Radium-223 in combination with docetaxel in patients with castration-resistant prostate cancer and bone metastases: a phase 1 dose escalation/randomised phase 2a trial

Author

Morris, Michael J., Loriot, Yohann, Sweeney, Christopher J., Fizazi, Karim, Ryan, Charles J., Shevrin, Daniel H., Antonarakis, Emmanuel S., Pandit-Taskar, Neeta, Deandreis, Désirée, Jacene, Heather A., Vesselle, Hubert, Petrenciuc, Oana, Lu, Cindy, Carrasquillo, Jorge A., and Higano, Celestia S.

Published
2019
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89. Cabozantinib Versus Mitoxantrone-prednisone in Symptomatic Metastatic Castration-resistant Prostate Cancer: A Randomized Phase 3 Trial with a Primary Pain Endpoint

Author

Basch, Ethan M., Scholz, Mark, de Bono, Johann S., Vogelzang, Nicholas, de Souza, Paul, Marx, Gavin, Vaishampayan, Ulka, George, Saby, Schwarz, James K., Antonarakis, Emmanuel S., O'Sullivan, Joseph M., Kalebasty, Arash Rezazadeh, Chi, Kim N., Dreicer, Robert, Hutson, Thomas E., Dueck, Amylou C., Bennett, Antonia V., Dayan, Erica, Mangeshkar, Milan, Holland, Jaymes, Weitzman, Aaron L., and Scher, Howard I.

Published
2019
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90. Natural Killer Cell Infiltration in Prostate Cancers Predict Improved Patient Outcomes

Author

Zorko, Nicholas A., primary, Makovec, Allison, additional, Elliott, Andrew, additional, Kellen, Samuel, additional, Lozada, John R., additional, Arafa, Ali T., additional, Felices, Martin, additional, Shackelford, Madison, additional, Barata, Pedro, additional, Zakharia, Yousef, additional, Narayan, Vivek, additional, Stein, Mark N., additional, Zarrabi, Kevin K., additional, Patniak, Akash, additional, Bilen, Mehmet A., additional, Radovich, Milan, additional, Sledge, George, additional, El-Deiry, Wafik S., additional, Heath, Elisabeth I., additional, Hoon, Dave S. B., additional, Nabhan, Chadi, additional, Miller, Jeffrey S., additional, Hwang, Justin H., additional, and Antonarakis, Emmanuel S., additional

Published
2024
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93. The Impact of Circulating Tumor Cell HOXB13 RNA Detection in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide

Author

Halabi, Susan, primary, Guo, Siyuan, additional, Park, Joseph J., additional, Nanus, David M., additional, George, Daniel J., additional, Antonarakis, Emmanuel S., additional, Danila, Daniel Costin, additional, Szmulewitz, Russell Zelig, additional, McDonnell, Donald P., additional, Norris, John D., additional, Lu, Changxue, additional, Luo, Jun, additional, and Armstrong, Andrew J., additional

Published
2024
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96. Targeted Inhibition of CYP11A1 in Castration-Resistant Prostate Cancer

Author

Fizazi, Karim, primary, Bernard-Tessier, Alice, additional, Roubaud, Guilhem, additional, Utriainen, Tapio, additional, Barthélémy, Philippe, additional, Fléchon, Aude, additional, van der Voet, Johannes, additional, Gravis, Gwenaëlle, additional, Ratta, Raffaele, additional, Jones, Robert, additional, Parikh, Omi, additional, Tanner, Minna, additional, Antonarakis, Emmanuel S., additional, Baldini, Capucine, additional, Peters, Niamh, additional, Garratt, Chris, additional, Ikonen, Tarja, additional, Pohjanjousi, Pasi, additional, Joensuu, Heikki, additional, and Cook, Natalie, additional

Published
2023
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97. MYC-driven increases in mitochondrial DNA copy number occur early and persist throughout prostatic cancer progression

Author

Chen, Jiayu, primary, Zheng, Qizhi, additional, Hicks, Jessica L., additional, Trabzonlu, Levent, additional, Ozbek, Busra, additional, Jones, Tracy, additional, Vaghasia, Ajay M., additional, Larman, Tatianna C., additional, Wang, Rulin, additional, Markowski, Mark C., additional, Denmeade, Sam R., additional, Pienta, Kenneth J., additional, Hruban, Ralph H., additional, Antonarakis, Emmanuel S., additional, Gupta, Anuj, additional, Dang, Chi V., additional, Yegnasubramanian, Srinivasan, additional, and De Marzo, Angelo M., additional

Published
2023
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98. Co-occurring BRCA2/SPOP Mutations Predict Exceptional Poly (ADP-ribose) Polymerase Inhibitor Sensitivity in Metastatic Castration-Resistant Prostate Cancer

Author

Orme, Jacob J., primary, Taza, Fadi, additional, De Sarkar, Navonil, additional, Tewari, Alok K., additional, Arsalan Naqvi, Syed, additional, Riaz, Irbaz B., additional, Childs, Daniel S., additional, Omar, Noha, additional, Adra, Nabil, additional, Ashkar, Ryan, additional, Cheng, Heather H., additional, Schweizer, Michael T., additional, Sokolova, Alexandra O., additional, Agarwal, Neeraj, additional, Barata, Pedro, additional, Sartor, Oliver, additional, Bastos, Diogo, additional, Smaletz, Oren, additional, Berchuck, Jacob E., additional, McClure, Heather, additional, Taplin, Mary-Ellen, additional, Aggarwal, Rahul, additional, Sternberg, Cora N., additional, Vlachostergios, Panagiotis J., additional, Alva, Ajjai S., additional, Mehra, Niven, additional, Nelson, Peter S., additional, Hwang, Justin, additional, Dehm, Scott M., additional, Shi, Qian, additional, Fleischmann, Zoe, additional, Sokol, Ethan S., additional, Elliott, Andrew, additional, Huang, Haojie, additional, Bryce, Alan, additional, Marshall, Catherine H., additional, and Antonarakis, Emmanuel S., additional

Published
2023
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99. Diverse AR-V7 cistromes in castration-resistant prostate cancer are governed by HoxB13

Author

Chen, Zhong, Wu, Dayong, Thomas-Ahner, Jennifer M., Lu, Changxue, Zhao, Pei, Zhang, Qingfu, Geraghty, Connor, Yan, Pearlly S., Hankey, William, Sunkel, Benjamin, Cheng, Xiaolong, Antonarakis, Emmanuel S., Wang, Qi-En, Liu, Zhihua, Huang, Tim H.-M., Jin, Victor X., Clinton, Steven K., Luo, Jun, Huang, Jiaoti, and Wang, Qianben

Published
2018

100. PARP inhibitors: What urologists need to know

Author

Antonarakis, Emmanuel S.

Subjects
Development and progression, Genetic aspects, Cancer genetics -- Genetic aspects -- Development and progression, DNA damage -- Genetic aspects, Olaparib, Cell death -- Genetic aspects, Pembrolizumab, Antineoplastic agents, Cancer -- Genetic aspects, Antimitotic agents
Abstract

In May 2020, the FDA approved the oral poly (ADP-ribose) polymerase (PARP) inhibitors rucaparib (Rubraca) and olaparib (Lynparza) for the treatment of metastatic castration-resistant prostate cancer. These 2 novel treatments [...]

Published
2021

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