Article
Multidisciplinary Sciences
Changsheng Huang, Shengxiang Ren, Yaqi Chen, Anyi Liu, Qi Wu, Tao Jiang, Panjing Lv, Da Song, Fuqing Hu, Jingqing Lan, Li Sun, Xue Zheng, Xuelai Luo, Qian Chu, Keyi Jia, Yan Li, Jun Wang, Caicun Zou, Junbo Hu, Guihua Wang
Summary: This research discovered that PD-L1 K162 was methylated by SETD7 and demethylated by LSD2. Additionally, PD-L1 K162 methylation controlled the PD1/PD-L1 interaction and significantly enhanced the suppression of T cell activity in controlling cancer immune surveillance. The study demonstrated that PD-L1 hypermethylation was the key mechanism for anti-PD-L1 therapy resistance, identified PD-L1 K162 methylation as a negative predictive marker for anti-PD-1 treatment in patients with non-small cell lung cancer, and showed that the PD-L1 K162 methylation:PD-L1 ratio was a more accurate biomarker for predicting anti-PD-(L)1 therapy sensitivity.
Review
Biochemistry & Molecular Biology
Enrico Munari, Francesca R. Mariotti, Linda Quatrini, Pietro Bertoglio, Nicola Tumino, Paola Vacca, Albino Eccher, Francesco Ciompi, Matteo Brunelli, Guido Martignoni, Giuseppe Bogina, Lorenzo Moretta
Summary: Immune evasion is a crucial strategy adopted by tumor cells to promote survival and metastasis, with PD-1 playing a major role in inhibiting immune responses. Targeting the PD-1/PD-L1 axis has been a significant breakthrough in cancer treatment, representing unprecedented success in various cancer types. Further research on mechanisms regulating PD-1 expression and signaling in tumors is needed to improve therapeutic efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Laure Chardin, Alexandra Leary
Summary: Ovarian cancer is a highly lethal gynecologic malignancy with a high recurrence rate, despite many patients responding effectively to current treatments. In order to improve outcomes, further research into the immune microenvironment and the development of effective therapies are urgently needed.
FRONTIERS IN ONCOLOGY
(2021)
Review
Immunology
Mengke Niu, Yiming Liu, Ming Yi, Dechao Jiao, Kongming Wu
Summary: The immune checkpoint pathway involving PD-1 and PD-L1 plays a crucial role in inhibiting T-cell proliferation and function, affecting antitumor immune responses. Alternative forms of PD-1/PD-L1, such as sPD-1/sPD-L1 and exoPD-L1, have been detected in cancer patients and may have significant biological activities.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Yanyan Zhang, Shuyi Zhu, Yuanyuan Du, Fan Xu, Wenbo Sun, Zhi Xu, Xiumei Wang, Peipei Qian, Qin Zhang, Jifeng Feng, Yong Xu
Summary: This study elucidates the molecular mechanism by which tumorous RelB contributes to immune evasion by inhibiting T cell immunity through the amplification of the PD-L1/PD-1-mediated immune checkpoint.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Review
Immunology
Ali Razaghi, Mickael Durand-Dubief, Nele Brusselaers, Mikael Bjornstedt
Summary: PD-1 and PD-L1 play crucial roles in immune regulation and can be targeted for cancer treatment. Blocking PD-1/PD-L1 can enhance tumor recognition by activated T cells and combining it with type I interferon (IFN) can further improve therapeutic efficacy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Plant Sciences
Myong Hak Ri, Juan Ma, Xuejun Jin
Summary: This study reviews the pharmacological effects of natural products, raw extracts, and traditional medicines associated with the PD-1/PD-L1 axis in cancer immunotherapy, particularly focusing on PD-L1. It was found that several natural products and traditional medicines have diverse and multi-functional effects that can improve strategies for anti-PD-1/PD-L1 therapy, but further research and exploration are needed.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Review
Cell Biology
Mateusz Kciuk, Damian Kolat, Zaneta Kaluzinska-Kolat, Mateusz Gawrysiak, Rafal Drozda, Ismail Celik, Renata Kontek
Summary: The application of immunotherapy for cancer treatment is expanding rapidly. Combining immunotherapeutic agents with different treatments can enhance the clinical response in patients who have developed resistance to monotherapy. Chemotherapeutic drugs that induce DNA damage often increase the expression of PD-L1, which can be used by cancer cells to evade immune surveillance. Targeting PD-L1 on cancer cells can restore the immune-reactive tumor microenvironment, making the tumor more susceptible to combined therapies. This review discusses the recent advances in understanding how DDR regulates PD-L1 expression and the impact of certain chemotherapeutic drugs on the anti-tumor immune response.
Article
Oncology
LeAnne Young, Shanda Finnigan, Howard Streicher, Helen X. Chen, James Murray, H. Nida Sen, Elad Sharon
Summary: Ocular adverse events are rare complications of PD-1/PD-L1 inhibitor therapy, but can be severe enough to cause treatment discontinuation or delay. Proper evaluation by eye specialists is necessary in managing these adverse events.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Medicine, Research & Experimental
Elina Khatoon, Dey Parama, Aviral Kumar, Mohammed S. Alqahtani, Mohamed Abbas, Sosmitha Girisa, Gautam Sethi, Ajaikumar B. Kunnumakkara
Summary: Ovarian cancer is a deadly gynecological cancer with a low survival rate. Recent advancements in immunotherapy, particularly targeting the PD-1/PD-L1 axis, have shown promise in enhancing anti-tumor activity. Combinatorial treatment with small molecule inhibitors has also shown improved efficacy.
Review
Oncology
Zi Yin, Min Yu, Tingting Ma, Chuanzhao Zhang, Shanzhou Huang, Mohammad Reza Karimzadeh, Amir Abaas Momtazi-Borojeni, Sheng Chen
Summary: Exosomes, specifically those derived from cancer cells, contain immunosuppressive proteins such as PD-L1, which can hinder immune responses and promote tumor progression. Blocking the interaction between PD-1 and PD-L1 can enhance the efficacy of cancer treatment by restoring anti-tumor immunity.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Nutrition & Dietetics
Yuqian Wang, Lingeng Lu, Changquan Ling, Ping Zhang, Rui Han
Summary: This study proposes a novel therapeutic strategy for breast cancer treatment by combining a diet containing HDAC2 inhibitors with PD-1/PD-L1 inhibitors, offering promising possibilities for improving treatment outcomes.
Article
Chemistry, Multidisciplinary
Weijing Yang, Meng Zhang, Jinjie Zhang, Yanlong Liu, Jie Ning, Jing Yang, Zhenzhong Zhang, Lin Hou, Xiaoyuan Chen
Summary: Targeting pre-activated T cells with immune checkpoint blockade through sequential therapy enhances immune response and improves antitumor activity.
Review
Oncology
Chao Cheng, Lingdun Zhuge, Xin Xiao, Siyuan Luan, Yong Yuan
Summary: As the predominant treatment option for advanced esophageal cancer, PD-1 and PD-L1 inhibitors provide new hope to clinical practice. However, some patients do not respond to this therapy and most initially sensitive patients eventually develop resistance. Therefore, it is critical to understand the mechanisms of resistance and explore efficient strategies to overcome it, in order to expand the benefit of immunotherapy.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Yasser Tabana, Isobel S. Okoye, Arno Siraki, Shokrollah Elahi, Khaled H. Barakat
Summary: Breast cancer poses a significant global problem, with recent focus on immunotherapy as a new approach to treatment. However, there are limitations to immune checkpoint inhibitors in treating breast cancer, leading researchers to explore novel immunological targets to modulate the tumor immune microenvironment.
FRONTIERS IN ONCOLOGY
(2021)
Review
Endocrinology & Metabolism
Samuel Denmeade, Emmanuel S. Antonarakis, Mark C. Markowski
Summary: Bipolar androgen therapy (BAT) is a new treatment concept that can be safely administered to asymptomatic patients with metastatic castrate-resistant prostate cancer. BAT produces sustained prostate-specific antigen and objective responses in 30%-40% of patients and can resensitize and prolong response to subsequent antiandrogen therapy.
Article
Endocrinology & Metabolism
Emmanuel S. Antonarakis, Marni Tierno, Virginia Fisher, Hanna Tukachinsky, Sonja Alexander, Omar Hamdani, Matthew C. Hiemenz, Richard S. P. Huang, Geoffrey R. Oxnard, Ryon P. Graf
Summary: Liquid biopsy is a powerful tool for guiding treatment decisions for metastatic prostate cancer patients with difficult-to-biopsy tumors, yet its efficacy is limited by the tumor fraction of circulating tumor DNA. This study validated and provided additional resolution for clinicians to anticipate the probability of successful liquid biopsy profiling based on commonly assessed clinical and laboratory features. Results showed that PSA levels, blood markers, and timing of liquid biopsy collection were strongly associated with the tumor fraction in liquid biopsy samples.
Editorial Material
Urology & Nephrology
Editorial Eugene Shenderov, Emmanuel S. Antonarakis
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
Biochemistry & Molecular Biology
Nima Nabavi, Seied Rabi Mahdavi, Mohammad Afshar Ardalan, Mohsen Chamanara, Reza Mosaed, Aline Lara, Diogo Bastos, Sara Harsini, Emran Askari, Pedro Isaacsson Velho, Hamed Bagheri
Summary: Androgen deprivation therapy (ADT) is the main treatment for advanced prostate cancer, but the development of castration-resistant prostate cancer is inevitable. Using novel hormonal agents may have long-term toxicities and trigger the selection of androgen receptor-independent cells. Bipolar androgen therapy (BAT) is a promising approach that involves alternating testosterone levels to inhibit prostate cancer growth and re-sensitize patients to previous therapies.
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.