Article
Oncology
Yangyang Kong, Chang Xu, Xiaohui Sun, Hao Sun, Xiaotong Zhao, Ningning He, Kaihua Ji, Qin Wang, Liqing Du, Jinhan Wang, Manman Zhang, Yang Liu, Yan Wang, Qiang Liu
Summary: The study demonstrated that olaparib and ML216 could enhance the radiosensitivity of NSCLC cells, especially in cells sensitive to olaparib. Furthermore, combining olaparib with ML216 showed synergistic radiosensitization in olaparib-resistant cells.
CANCER BIOLOGY & MEDICINE
(2022)
Article
Oncology
T. Hedley Carr, Carrie Adelman, Alan Barnicle, Iwanka Kozarewa, Sally Luke, Zhongwu Lai, Sally Hollis, Brian Dougherty, Elizabeth A. Harrington, Jinyu Kang, Fred Saad, Nuria Sala, Antoine Thiery-Vuillemin, Noel W. Clarke, Darren Hodgson, J. Carl Barrett
Summary: The study showed that regardless of HRR status, mCRPC patients benefit from olaparib and abiraterone treatment, with the value of ctDNA testing highlighted as a valuable complement to tumor tissue sequencing.
Article
Oncology
Kim N. Chi, Neil Fleshner, Vincenzo Emanuele Chiuri, Siska Van Bruwaene, Jason Hafron, Douglas G. McNeel, Peter De Porre, Raymond Scott Maul, Mahesh Daksh, Xiaogang Zhong, Gary E. Mason, Ronald F. Tutrone
Summary: Niraparib, a selective PARP1 and PARP2 inhibitor, has been evaluated in combination therapy for metastatic castration-resistant prostate cancer patients with homologous recombination repair gene alterations. The combination of Niraparib with abiraterone acetate plus prednisone showed promising efficacy and manageable safety profile in this patient population.
Article
Cell Biology
Sayeh Saravi, Zena Alizzi, Sabrina Tosi, Marcia Hall, Emmanouil Karteris
Summary: This study aimed to assess the effects of the PARPi rucaparib in vitro on cell lines with BRCA2 mutations, revealing significant impact on DNA damage and the mTOR pathway of PEO1 cells.
Review
Biotechnology & Applied Microbiology
Alexis LeVee, Ching Ying Lin, Edwin Posadas, Robert Figlin, Neil A. Bhowmick, Dolores Di Vizio, Leigh Ellis, Charlos J. Rosser, Michael R. Freeman, Dan Theodorescu, Stephen J. Freedland, Jun Gong
Summary: Research has shown that PARPi plays a crucial role in the treatment of mCRPC patients, particularly those with HHR gene mutations. Olaparib, as the first PARP inhibitor, has been approved for use in male mCRPC patients.
ONCOTARGETS AND THERAPY
(2021)
Article
Medicine, Research & Experimental
Li-Min Wang, Pingyuan Wang, Xiao-Min Chen, Hui Yang, Shan-Shan Song, Zilan Song, Li Jia, Hua-Dong Chen, Xu-Bin Bao, Ne Guo, Xia-Juan Huan, Yong Xi, Yan-Yan Shen, Xin-Ying Yang, Yi Su, Yi-Ming Sun, Ying-Lei Gao, Yi Chen, Jian Ding, Jing-Yu Lang, Ze-Hong Miao, Ao Zhang, Jin-Xue He
Summary: The next-generation PARPi thioparib shows strong antitumor activity against PARPi-sensitive and -resistant HR-deficient cells, inducing DNA damage, replication stress, cell cycle arrest, and apoptosis. It also inhibits HR-mediated DNA repair, activates STAT1 and induces type I interferon production, leading to tumor growth inhibition.
EMBO MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Kristie-Ann Dickson, Tao Xie, Christian Evenhuis, Yue Ma, Deborah J. Marsh
Summary: PARP inhibitors have shown efficacy in treating tumors with BRCA gene defects, improving survival outcomes. Variability exists between different PARP inhibitors in terms of chemical structure, toxicity, and cell survival, with acquired resistance being a concerning issue that needs further exploration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Saptarshi Sinha, Subhajit Chatterjee, Subarno Paul, Biswajit Das, Somya Ranjan Dash, Chinmay Das, Chanakya Nath Kundu
Summary: The combination of RES and OLA enhances cell death in HR-proficient breast cancer cells by increasing DNA damage and inhibiting the HR pathway.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Urology & Nephrology
Konrad H. Stopsack
Summary: The PROfound trial found that treatment with the PARP inhibitor olaparib benefits men with metastatic castration-resistant prostate cancer harboring alterations in 15 different DNA repair genes. However, the benefit of olaparib was less significant, if present at all, for men with prostate cancer harboring non-BRCA DNA repair alterations compared to those with BRCA alterations.
Article
Oncology
H. P. Eikesdal, S. Yndestad, A. Elzawahry, A. Llop-Guevara, B. Gilje, E. S. Blix, H. Espelid, S. Lundgren, J. Geisler, G. Vagstad, A. Venizelos, L. Minsaas, B. Leirvaag, E. G. Gudlaugsson, O. K. Vintermyr, H. S. Aase, T. Aas, J. Balmana, V Serra, E. A. M. Janssen, S. Knappskog, P. E. Lonning
Summary: In primary treatment-naive triple negative breast cancer patients, olaparib showed a high clinical response rate in patients with homologous recombination deficiency, surpassing those without this defect. This demonstrates the effectiveness of olaparib in this population.
ANNALS OF ONCOLOGY
(2021)
Article
Oncology
F. Guffanti, M. F. Alvisi, A. Anastasia, F. Ricci, M. Chiappa, A. Llop-Guevara, V Serra, R. Fruscio, A. Degasperi, S. Nik-Zainal, M. R. Bani, M. Lupia, R. Giavazzi, E. Rulli, G. Damia
Summary: This study demonstrates that the RAD51 foci score can predict the response to olaparib in ovarian cancer patients, providing a simple and feasible biomarker for clinical application. Furthermore, the findings emphasize the importance of ovarian cancer patient-derived xenografts (PDXs) as a reliable tool for identifying and validating biomarkers of response to therapy.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Sophie Gilbert, Benjamin Peant, Anne-Marie Mes-Masson, Fred Saad
Summary: Inhibition of IKK-epsilon expression or using IKK-epsilon inhibitors can decrease proliferation and tumor volume of castrate resistant prostate cancer cells. Moreover, these inhibitors can induce senescence, DNA damage, and genomic instability. Combining Amlexanox and Olaparib can enhance the anti-cancer effects.
Review
Oncology
Lorena Incorvaia, Alessandro Perez, Claudia Marchetti, Chiara Brando, Valerio Gristina, Daniela Cancelliere, Alessia Pivetti, Silvia Contino, Emilia Di Giovanni, Nadia Barraco, Marco Bono, Ambra Giurintano, Tancredi Didier Bazan Russo, Andrea Gottardo, Sofia Cutaia, Erika Pedone, Marta Peri, Lidia Rita Corsini, Daniele Fanale, Antonio Galvano, Giovanni Scambia, Giuseppe Badalamenti, Antonio Russo, Viviana Bazan
Summary: BRCA1 and BRCA2 deleterious variants have been the main biomarkers for the efficacy of PARP inhibitors in breast cancer. However, with the increasing number of individuals seeking counseling and multigene panel testing, as well as the expanding approval of PARP inhibitors beyond BRCA1/BRCA2 variants, there is a strong need for non-BRCA biomarkers. Current testing and assays have limitations, and different approaches to identify the causes of HRD are not interchangeable. The deeper understanding of proteins involved in HRR, beyond BRCA, brings possibilities for successful non-BRCA, HRD-PARPi synthetic lethality, but also highlights the need for better definition of HRD biomarkers for predicting the magnitude of PARP inhibitor benefit.
CANCER TREATMENT REVIEWS
(2023)
Review
Oncology
Maximillian S. Wu, Hanan Goldberg
Summary: Prostate cancer is a common cancer type with strong genetic associations, and mCRPC is resistant to standard therapies. Rucaparib, a PARP inhibitor, has shown promising results in treating mCRPC patients with BRCA1/2 mutations, with similar safety profiles to other PARP inhibitors. Further research is needed to investigate metabolic differences and efficacy in other cancer types.
CANCER MANAGEMENT AND RESEARCH
(2022)
Article
Oncology
Anne Patsouris, Kadija Diop, Olivier Tredan, Daniel Nenciu, Anthony Goncalves, Monica Arnedos, Marie-Paule Sablin, Pascal Jezequel, Marta Jimenez, Nathalie Droin, Ivan Bieche, Celine Callens, Andrea Loehr, Cecile Vicier, Catherine Guerin, Thomas Filleron, Fabrice Andre
Summary: The RUBY study evaluated the efficacy of rucaparib in HER2-negative metastatic breast cancer patients, indicating that some patients without germline BRCA1/2 mutation could benefit from PARP inhibitors. However, additional biomarkers are needed to selectively identify potential responders.
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Oncology
Harsimar B. Kaur, Thiago Vidotto, Adrianna A. Mendes, Daniela C. Salles, William B. Isaacs, Emmanuel S. Antonarakis, Tamara L. Lotan
Summary: This study found that prostate tumors carrying BRCA2 or ATM gene mutations are not associated with elevated T-cell density, but measures of genomic scarring may be related to increased tumor-infiltrating T-cells.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Oncology
Mark C. Markowski, Sushant Kachhap, Angelo M. De Marzo, Laura A. Sena, Jun Luo, Samuel R. Denmeade, Emmanuel S. Antonarakis
Summary: Bipolar androgen therapy (BAT) is a novel treatment strategy for patients with metastatic castration-resistant prostate cancer (mCRPC) that has shown deep PSA responses. Our retrospective analysis found that almost all patients with extreme PSA responses to BAT harbored pathogenic mutations in TP53 and/or a homologous recombination DNA repair gene. These findings suggest that BAT may be most beneficial for mCRPC patients with DNA repair deficiencies.
CLINICAL GENITOURINARY CANCER
(2022)
Editorial Material
Urology & Nephrology
Editorial Eugene Shenderov, Emmanuel S. Antonarakis
Article
Oncology
Xiaolei Shi, Abderrahman Day, Hannah E. Bergom, Sydney Tape, Sylvan C. Baca, Zoi E. Sychev, Gabrianne Larson, Asha Bozicevich, Justin M. Drake, Nicholas Zorko, Jinhua Wang, Charles J. Ryan, Emmanuel S. Antonarakis, Justin Hwang
Summary: The study identifies B7-H3 as an immune checkpoint overexpressed in prostate cancer, particularly in metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide-resistant mCRPC cells show increased expression of B7-H3, and it is associated with resistance signaling pathways. The gene network of B7-H3 is strongly correlated with androgen receptor (AR) and its co-factors, suggesting potential therapeutic targets for mCRPC.
NPJ PRECISION 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.