Article
Oncology
Ravi A. A. Madan, Jason M. M. Redman, Fatima Karzai, William L. L. Dahut, Lisa Cordes, Farhad Fakhrejahani, Tuyen Vu, Nadeem Sheikh, Jeffrey Schlom, James L. L. Gulley
Summary: Therapeutic cancer vaccines have shown clinical benefit in mCRPC patients, but the effects of sequential checkpoint inhibitors after therapeutic vaccine are not well understood. A study using avelumab as anti-PD-L1 therapy in mCRPC patients with previous therapeutic vaccine showed disappointing results, indicating a poor response in this patient population.
JOURNAL OF IMMUNOTHERAPY
(2023)
Article
Biology
Roberta Coletti, Andrea Pugliese, Luca Marchetti
Summary: This study analyzes the potential effect of immunotherapies on castration-resistant prostate cancer, showing limited impact of dendritic vaccine sipuleucel-T and potential effectiveness of ipilimumab in controlling and eliminating androgen-independent prostate cancer. Mathematical models suggest that under continuous administration of ipilimumab, the system may be in a bistable situation, with the outcome potentially influenced by the schedule of periodic treatments.
JOURNAL OF THEORETICAL BIOLOGY
(2021)
Review
Oncology
Canling Lin, Yonghui Chen, Liji Shi, Huarong Lin, Hongmei Xia, Weihua Yin
Summary: Prostate cancer is a significant disease worldwide, and its incidence is increasing in China. Despite the efficacy of chemotherapy agents, treatment failure can occur, leading to castration-resistant prostate cancer. Due to limited treatment options, bio-immunotherapy targeting the prostate microenvironment has become an important option for advanced prostate cancer. This study investigates the role of three types of bio-immunotherapies in castrate-resistant prostate cancer, providing insights for clinical treatment.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Oncology
Ravi A. Madan, Marijo Bilusic, Mark N. Stein, Renee N. Donahue, Philip M. Arlen, Fatima Karzai, Elizabeth Plimack, Yu-Ning Wong, Daniel M. Geynisman, Matthew Zibelman, Tina Mayer, Julius Strauss, Gang Chen, Myrna Rauckhorst, Sheri McMahon, Anna Couvillon, Seth Steinberg, William D. Figg, William L. Dahut, Jeffrey Schlom, James L. Gulley
Summary: This study compared the efficacy of Flutamide with or without PROSTVAC in patients with non-metastatic castration resistant prostate cancer, and the results showed that the addition of PROSTVAC did not improve patient outcomes.
Review
Oncology
Dhruv Bansal, Melissa A. Reimers, Eric M. Knoche, Russell K. Pachynski
Summary: Immunotherapy has revolutionized the treatment of various malignancies, but its efficacy in prostate cancer remains limited due to the immunosuppressive tumor microenvironment. Clinical trials are now focusing on combination therapies to enhance anti-tumor immune responses, including immunomodulatory agents and conventional treatments. Promising new approaches, such as vaccine-based therapies and checkpoint inhibitors, are being explored to improve outcomes for patients with metastatic castrate-resistant prostate cancer.
Article
Biochemistry & Molecular Biology
Raquibul Hannan, Michael J. Dohopolski, Laurentiu M. Pop, Samantha Mannala, Lori Watumull, Dana Mathews, Ang Gao, Aurelie Garant, Yull E. Arriaga, Isaac Bowman, Jin-Sung Chung, Jing Wang, Kiyoshi Ariizumi, Chul Ahn, Robert Timmerman, Kevin Courtney
Summary: The addition of concurrent stereotactic ablative radiotherapy (SAbR) did not significantly increase the time to progression in patients with metastatic castrate-resistant prostate cancer (mCRPCA) treated with sipuleucel-T, but induced cellular and humoral immune responses.
Article
Oncology
Masanori Noguchi, Kiyohide Fujimoto, Gaku Arai, Hiroji Uemura, Katsuyoshi Hashine, Hiroaki Matsumoto, Satoshi Fukasawa, Yasuo Kohjimoto, Hideomi Nakatsu, Atsushi Takenaka, Masato Fujisawa, Hirotsugu Uemura, Seiji Naito, Shin Egawa, Hiroyuki Fujimoto, Shiro Hinotsu, Kyogo Itoh
Summary: This study investigated the impact of personalized peptide vaccination (PPV) on overall survival (OS) in HLA-A24-positive patients with castration-resistant prostate cancer (CRPC) who failed docetaxel chemotherapy. The results showed that PPV did not prolong OS overall, but subgroup analysis revealed survival benefits in patients with a lower proportion of neutrophils or a higher proportion of lymphocytes at baseline.
Article
Oncology
Gilberto Filaci, Daniela Fenoglio, Franco Nole, Elisa Zanardi, Laura Tomasello, Massimo Aglietta, Gianluca Del Conte, Joan Carles, Rafael Morales-Barrera, Pamela Guglielmini, Giorgio Scagliotti, Alessio Signori, Alessia Parodi, Francesca Kalli, Giuseppina Astone, Francesca Ferrera, Tiziana Altosole, Giuseppina Lamperti, Domenico Criscuolo, Francesco Gianese, Francesco Boccardo
Summary: This study aimed to compare the safety and immunological response of three GX301 regimens in metastatic castration-resistant prostate cancer patients who had response/disease stability after docetaxel chemotherapy. Results showed that the rate of immunological responders was proportionally related to the number of immunizations, suggesting that regimens with a higher number of administrations may lead to better immunological outcomes.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Oncology
Alberto Martini, Anish B. Parikh, John P. Sfakianos, Francesco Montorsi, Matthew D. Galsky, William K. Oh, Che-Kai Tsao
Summary: Docetaxel is widely used in mCRPC, but its optimal use is unclear. This study aimed to create a predictive model for Docetaxel toxicity-related discontinuation (TRDD) using data from three clinical trials. The model identified three risk groups for TRDD, helping clinicians balance treatment toxicity and efficacy.
PROSTATE CANCER AND PROSTATIC DISEASES
(2021)
Review
Oncology
Christina Steinbach, Almas Merchant, Alexandru-Teodor Zaharie, Peter Horak, Maximilian Marhold, Michael Krainer
Summary: Prostate cancer is a leading cause of cancer-related deaths among men in the US and Europe. Conventional treatments have limitations, while immunotherapy, specifically cellular immunotherapy and chimeric antigen receptors (CAR) T-cell therapy, shows promise in targeting malignant cells. The complex microenvironment of the tumor greatly affects the success or failure of immunotherapies in prostate cancer.
Review
Cell Biology
Vincenza Conteduca, Alessandra Mosca, Nicole Brighi, Ugo de Giorgi, Pasquale Rescigno
Summary: Prostate cancer is a common cancer in men and patients may develop metastatic disease after radical treatments. Prognostic biomarkers are urgently needed to define patients' risk of cancer-related death.
Article
Oncology
Emmanuel S. Antonarakis, Sumit K. Subudhi, Christopher M. Pieczonka, Lawrence I. Karsh, David I. Quinn, Jason M. Hafron, Helen M. Wilfehrt, Matthew Harmon, Nadeem A. Sheikh, Neal D. Shore, Daniel P. Petrylak
Summary: The purpose of this study was to investigate the impact of sequential or concurrent administration of androgen receptor-targeting agents (ARTAs) on sipuleucel-T immune response and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC). The results showed that the median OS remained consistent regardless of whether the agents were administered sequentially or concurrently, and sipuleucel-T induced an immunologic prime-boost effect after initial exposure, even when combined with ARTAs.
CLINICAL CANCER RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Nityam Rathi, Taylor Ryan McFarland, Roberto Nussenzveig, Neeraj Agarwal, Umang Swami
Summary: Immunotherapies have shown success in treating multiple cancer types, but have faced challenges in prostate cancer. The immune evasion in prostate cancer is attributed to intrinsic tumor factors, immunosuppressive tumor microenvironment, and host factors. Researchers are exploring ways to transform prostate cancer from a 'cold' tumor to a 'hot' tumor through various approaches, including immune checkpoint inhibitors and other upcoming immunotherapies.
Article
Oncology
Douglas G. McNeel, Jens C. Eickhoff, Ellen Wargowski, Laura E. Johnson, Christos E. Kyriakopoulos, Hamid Emamekhoo, Joshua M. Lang, Mary Jane Brennan, Glenn Liu
Summary: The combination of programmed cell death 1 blockade and MVI-816 is safe and can enhance tumor-specific T cells, resulting in a favorable 6-month disease control rate. The occurrence of immune-related adverse events is significantly associated with prolonged time on treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Giandomenico Roviello, Martina Catalano, Carlotta Ottanelli, Roberta Giorgione, Virginia Rossi, Elisabetta Gambale, Chiara Casadei, Ugo De Giorgi, Lorenzo Antonuzzo
Summary: The treatment landscape for metastatic castration-resistant prostate cancer has evolved with several drug classes available. Lack of validated predictive biomarkers makes therapeutic choice difficult. The location of metastatic site may be a valid criterion for selecting among treatment options.
Editorial Material
Urology & Nephrology
Editorial Eugene Shenderov, Emmanuel S. Antonarakis
Article
Oncology
Matthew P. Deek, Kim Van der Eecken, Philip Sutera, Rebecca A. Deek, Valerie Fonteyne, Adrianna A. Mendes, Karel Decaestecker, Ana Ponce Kiess, Nicolaas Lumen, Ryan Phillips, Aurelie De Bruycker, Mark Mishra, Zaker Rana, Jason Molitoris, Bieke Lambert, Louke Delrue, Hailun Wang, Kathryn Lowe, Sofie Verbeke, Jo Van Dorpe, Renee Bultijnck, Geert Villeirs, Kathia De Man, Filip Ameye, Daniel Y. Song, Theodore DeWeese, Channing J. Paller, Felix Y. Feng, Alexander Wyatt, Kenneth J. Pienta, Maximillian Diehn, Soren M. Bentzen, Steven Joniau, Friedl Vanhaverbeke, Gert De Meerleer, Emmanuel S. Antonarakis, Tamara L. Lotan, Alejandro Berlin, Shankar Siva, Piet Ost, Phuoc T. Tran
Summary: This study presents the long-term outcomes of metastasis-directed therapy (MDT) in oligometastatic castration-sensitive prostate cancer (omCSPC) and investigates the impact of high-risk mutations on treatment outcomes.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Endocrinology & Metabolism
Christopher T. Su, Emily Nizialek, Jacob E. Berchuck, Panagiotis J. Vlachostergios, Ryan Ashkar, Alexandra Sokolova, Pedro C. Barata, Rahul R. Aggarwal, Rana R. McKay, Neeraj Agarwal, Heather M. McClure, Nellie Nafissi, Alan H. Bryce, Oliver Sartor, Nicolas Sayegh, Heather H. Cheng, Nabil Adra, Cora N. Sternberg, Mary-Ellen Taplin, Marcin Cieslik, Ajjai S. Alva, Emmanuel S. Antonarakis
Summary: PARP inhibitors (PARPi) are standard treatment for mCRPC patients with specific mutations, but response may differ in patients with ATM and BRCA2 mutations. We investigated differences in response to taxanes, which may inform treatment sequencing decisions.
Article
Oncology
Santosh Gupta, Susan Halabi, Qian Yang, Akash Roy, Alisa Tubbs, Yamini Gore, Daniel J. George, David M. Nanus, Emmanuel S. Antonarakis, Daniel C. Danila, Russell Z. Szmulewitz, Richard Wenstrup, Andrew J. Armstrong
Summary: PSMA-targeted radioligand therapy has significantly improved clinical outcomes in men with mCRPC. A liquid biopsy characterizing PSMA expression could be useful in guiding optimal therapy.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Emmanuel S. Antonarakis, Sumit K. Subudhi, Christopher M. Pieczonka, Lawrence I. Karsh, David I. Quinn, Jason M. Hafron, Helen M. Wilfehrt, Matthew Harmon, Nadeem A. Sheikh, Neal D. Shore, Daniel P. Petrylak
Summary: The purpose of this study was to investigate the impact of sequential or concurrent administration of androgen receptor-targeting agents (ARTAs) on sipuleucel-T immune response and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC). The results showed that the median OS remained consistent regardless of whether the agents were administered sequentially or concurrently, and sipuleucel-T induced an immunologic prime-boost effect after initial exposure, even when combined with ARTAs.
CLINICAL CANCER RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Adel Mandl, Mark C. Markowski, Michael A. Carducci, Emmanuel S. Antonarakis
Summary: The BET family of proteins are crucial in activating oncogenic networks in different cancers. Therapeutic targeting of BET proteins has shown potential in treating metastatic castration-resistant prostate cancer. However, clinical success has been limited due to treatment-associated toxicities, drug resistance, and a lack of biomarkers.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2023)
Article
Oncology
Michael J. Morris, Glenn Heller, David W. Hillman, Olivia Bobek, Charles Ryan, Emmanuel S. Antonarakis, Alan H. Bryce, Olwen Hahn, Himisha Beltran, Andrew J. Armstrong, Lawrence Schwartz, Lionel D. Lewis, Jan H. Beumer, Brooke Langevin, Eric C. McGary, Paul T. Mehan, Amir Goldkorn, Bruce J. Roth, Han Xiao, Colleen Watt, Mary-Ellen Taplin, Susan Halabi, Eric J. Small
Summary: The purpose of this study was to determine whether the addition of abiraterone acetate and prednisone (AAP) to enzalutamide prolongs overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) in the first-line setting. The results showed that the addition of AAP did not provide a statistically significant benefit in OS compared to enzalutamide treatment alone.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Emmanuel S. Antonarakis, Wassim Abida
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Emmanuel S. Antonarakis, Se Hoon Park, Jeffrey C. Goh, Sang Joon Shin, Jae Lyun Lee, Niven Mehra, Ray McDermott, Nuria Sala-Gonzalez, Peter C. Fong, Richard Greil, Margitta Retz, Juan Pablo Sade, Patricio Yanez, Yi-Hsiu Huang, Stephen D. Begbie, Rustem Airatovich Gafanov, Maria De Santis, Eli Rosenbaum, Michael P. Kolinsky, Felipe Rey, Kun-Yuan Chiu, Guilhem Roubaud, Gero Kramer, Makoto Sumitomo, Francesco Massari, Hiroyoshi Suzuki, Ping Qiu, Jinchun Zhang, Jeri Kim, Christian H. Poehlein, Evan Y. Yu
Summary: This study evaluated the efficacy of pembrolizumab plus olaparib compared to a next-generation hormonal agent (NHA) for heavily pretreated mCRPC patients. The results showed that pembrolizumab plus olaparib did not significantly improve rPFS or OS. The study was stopped for futility and no new safety signals were observed.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Endocrinology & Metabolism
Ali. T. T. Arafa, Leah. R. R. Blader, Karan Ramakrishna, Jeff Engle, Charles. J. J. Ryan, Nicholas. A. A. Zorko, Gautam Jha, Emmanuel. S. S. Antonarakis
Summary: This study evaluated the impact of androgen deprivation therapy (ADT) cessation in patients starting abiraterone for castration-resistant prostate cancer. The results showed that abiraterone alone was associated with comparable clinical outcomes to abiraterone plus ADT. Further prospective studies are needed to assess the impact of abiraterone alone on treatment outcomes and cost savings.
Review
Endocrinology & Metabolism
Ali T. T. Arafa, Aditya Jain, Pavel Skrobanek, Brad Humphrey, Jerry W. W. Froelich, Emmanuel S. S. Antonarakis
Summary: This study assessed the impact of Piflufolastat F-18 (18F-DCFPyL) prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging on clinical practice. The results showed that this technology significantly influenced the initial staging, biochemical recurrence, and restaging of metastatic prostate cancer.
Review
Oncology
Angela Y. Y. Jia, Ana P. Kiess, Qiubai Li, Emmanuel S. Antonarakis
Summary: The discovery of small molecules targeting the extracellular domain of PSMA has advanced diagnostic imaging and precision radiopharmaceutical therapies. This review presents existing data and ongoing clinical evaluations of PSMA-based imaging in the management of prostate cancer. It also discusses clinical studies on PSMA-based radiopharmaceutical therapy and forthcoming trials on early disease states. Multidisciplinary collaboration in trial design and therapeutic administration is crucial for the continued progress of this radiotheranostics field.
PROSTATE CANCER AND PROSTATIC DISEASES
(2023)
Review
Oncology
Sree M. Lanka, Nicholas A. Zorko, Emmanuel S. Antonarakis, Pedro C. Barata
Summary: The development of immune checkpoint inhibitors (ICIs) has revolutionized the treatment landscape of several genitourinary malignancies, but the utility of immunotherapies in prostate cancer has been limited due to its immunologically cold tumor terrain. Pembrolizumab is currently the only approved ICI for metastatic castration resistant prostate cancer (mCRPC) in a select group of patients. Future research is exploring combination approaches with ICIs and other treatments to enhance their efficacy in mCRPC. Additionally, alternative checkpoint inhibitors like B7-H3 hold promise in expanding the treatment options for mCRPC.
Article
Medicine, Research & Experimental
Laura A. Sena, Rajendra Kumar, David E. Sanin, Elizabeth A. Thompson, D. Marc Rosen, Susan L. Dalrymple, Lizamma Antony, Yuhan Yang, Carolina Gomes-Alexandre, Jessica L. Hicks, Tracy Jones, Kiara A. Bowers, Jillian N. Eskra, Jennifer Meyers, Anuj Gupta, Alyza Skaist, Srinivasan Yegnasubramanian, Jun Luo, W. Nathaniel Brennen, Sushant K. Kachhap, Emmanuel S. Antonarakis, Angelo M. De Marzo, John T. Isaacs, Mark C. Markowski, Samuel R. Denmeade
Summary: This study identifies high androgen receptor (AR) activity as a predictive biomarker for response to bipolar androgen therapy (BAT) and supports a treatment paradigm for prostate cancer involving alternating between AR inhibition and activation.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Urology & Nephrology
Mark C. Markowski, Hao Wang, Angelo M. De Marzo, Michael T. Schweizer, Emmanuel S. Antonarakis, Samuel R. Denmeade
Summary: Bipolar androgen therapy (BAT) may be a safe and effective treatment for prostate cancer that is resistant to testosterone suppression and has mutations in tumor suppressor genes. BAT can improve PSA50 response rate, progression-free survival, and overall survival, particularly in patients without prior chemotherapy.
EUROPEAN UROLOGY OPEN SCIENCE
(2022)
