Review
Oncology
Ahmed M. Elshazly, David A. Gewirtz
Summary: This paper investigates the autophagy forms induced in prostate cancer under androgen-targeted therapies and evaluates whether autophagy plays a central role in limiting the effectiveness of androgen deprivation therapies.
Article
Chemistry, Medicinal
Dong-Jin Hwang, Yali He, Suriyan Ponnusamy, Thirumagal Thiyagarajan, Michael L. Mohler, Ramesh Narayanan, Duane D. Miller
Summary: A major challenge in new drug discovery of androgen receptor antagonists is predicting the druggable properties necessary for potency and stability. This study synthesized new compounds with improved stability while maintaining potent antagonistic activity. Through a structure-activity relationship study, two compounds were found to be potent AR antagonists with improved in vivo pharmacokinetics and antiandrogen activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Dong-Jin Hwang, Yali He, Suriyan Ponnusamy, Thirumagal Thiyagarajan, Michael L. Mohler, Ramesh Narayanan, Duane D. Miller
Summary: A major challenge in new drug discovery is predicting the druggable properties of small molecules for potent and stable activity. In this study, new small molecules with improved stability and potent antagonistic activity against androgen receptor (AR) were synthesized. Structure-activity relationship (SAR) analysis identified two compounds with high efficacy as AR antagonists, exhibiting improved pharmacokinetics in vivo and antiandrogen activity in tumor xenograft models.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Sanjay Das, Nadine A. Friedrich, James Daniels, G. Cecilia Galvan, Jun Gong, Edwin Posadas, William Aronson, Stephen J. Freedland
Summary: This study compares public interest in FDA-approved drugs for advanced prostate cancer and finds that Bicalutamide remains relatively popular, especially among lower-income individuals, those without health insurance, and in states that did not expand Medicaid.
PROSTATE CANCER AND PROSTATIC DISEASES
(2023)
Article
Multidisciplinary Sciences
Mamta Parikh, Chengfei Liu, Chun-Yi Wu, Christopher P. Evans, Marc Dall'Era, Daniel Robles, Primo N. Lara, Neeraj Agarwal, Allen C. Gao, Chong-Xian Pan
Summary: The study aimed to evaluate the efficacy and tolerability of a novel reformulated orally-bioavailable niclosamide in combination with abiraterone and prednisone for castration-resistant prostate cancer. The results showed that this combination therapy demonstrated good tolerability and treatment response in patients, warranting further research.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Medicinal
Borui Kang, Madhusoodanan Mottamal, Qiu Zhong, Melyssa Bratton, Changde Zhang, Shanchun Guo, Ahamed Hossain, Peng Ma, Qiang Zhang, Guangdi Wang, Florastina Payton-Stewart
Summary: Niclosamide is effective in downregulating androgen receptor variants (AR-Vs) and can be used to treat enzalutamide and abiraterone-resistant prostate cancer. However, the poor pharmaceutical properties of niclosamide limit its systemic use. In this study, a series of niclosamide analogs were synthesized and evaluated for their anti-proliferative activity and downregulation of AR and AR-V7. Some of the analogs showed improved pharmacological properties and exhibited potent AR-V7 downregulation activity.
Review
Pharmacology & Pharmacy
Jinxiang Wang, Leli Zeng, Nisha Wu, Yanling Liang, Jie Jin, Mingming Fan, Xiaoju Lai, Zhe-Sheng Chen, Yihang Pan, Fangyin Zeng, Fan Deng
Summary: In this study, it was discovered that high expression of PHGDH is associated with enzalutamide resistance in castration-resistant prostate cancer (CRPC) cells. Knockdown of PHGDH inhibited the growth of enzalutamide-resistant CRPC cells and sensitized them to enzalutamide treatment. Moreover, pharmacological inhibition of PHGDH induced ferroptosis and overcame enzalutamide resistance both in vitro and in vivo. Therefore, targeting PHGDH and inducing ferroptosis could be a potential therapeutic strategy for overcoming enzalutamide resistance in CRPC.
DRUG RESISTANCE UPDATES
(2023)
Review
Endocrinology & Metabolism
Xianlu Zhang, Gejun Zhang, Jianfeng Wang, Jianbin Bi
Summary: The network meta-analysis indicated that second-generation androgen receptor inhibitors (ARIs) were superior to the conventional ARI, bicalutamide, in treating castration-resistant prostate cancer (CRPC). Among the three second-generation ARIs, enzalutamide and apalutamide demonstrated better therapeutic effects, while darolutamide was slightly less effective. Apalutamide showed a higher rate of adverse events, although no statistical significance was observed among these vital adverse events. Overall, all ARIs were well-tolerated, and these results could provide reference for clinical decisions and further direct comparison trials.
FRONTIERS IN ENDOCRINOLOGY
(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)
Article
Pharmacology & Pharmacy
Sisi Qin, Huanyao Gao, Wootae Kim, Huan Zhang, Yayun Gu, Krishna R. Kalari, Jason P. Sinnwell, Jodi A. Scholz, Fang Xie, Ping Yin, Jia Yu, Bo Qin, Yongxian Zhuang, Lixuan Wei, Winston Tan, Alan H. Bryce, Richard M. Weinshilboum, Liewei Wang
Summary: This study identified three drugs that could potentially be alternative treatments for abiraterone nonresponders in patients with metastatic castration-resistant prostate cancer. Additionally, eleven genes targeted by these drugs were associated with worse outcomes in both PROMOTE and Stand Up To Cancer cohorts. Further clinical investigation is needed to determine the efficacy of these alternative therapies.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Medicine, General & Internal
Ulka N. Vaishampayan, Lance K. Heilbrun, Paul Monk, Sheela Tejwani, Guru Sonpavde, Clara Hwang, Daryn Smith, Pallavi Jasti, Kimberlee Dobson, Brenda Dickow, Elisabeth I. Heath, Louie Semaan, Michael L. Cher, Joseph A. Fontana, Sreenivasa Chinni
Summary: This study found that enzalutamide combined with androgen deprivation therapy was more effective than bicalutamide for Black men with metastatic hormone-sensitive prostate cancer (mHSPC) in terms of the prostate-specific antigen response rate. The inclusion of enzalutamide in the treatment plan for mHSPC should be strongly considered based on these improved outcomes.
Article
Endocrinology & Metabolism
Yifan Zhang, Yuanpeng Liao, Mayao Luo, Yuedian Ye, Zhuofan Xu, Wenli Hou, Ruiyu Liu, Qiliang Zhai, Shidong Lv, Qiang Wei
Summary: The combination of AR degrader IU1 and AR antagonist enzalutamide synergistically promotes AR degradation and inhibits proliferation, induces apoptosis, and blocks the cell cycle in prostate cancer cells. Mechanistically, the combination treatment increases AR ubiquitination levels, resulting in the inhibitory effect on prostate cancer cells.
Article
Oncology
Jianqing Lin, Jacob Elkon, Brittany Ricart, Erica Palmer, Christian Zevallos-Delgado, Satish Noonepalle, Brooke Burgess, Robert Siegel, Yan Ma, Alejandro Villagra
Summary: The combination of Entinostat and standard dose of enzalutamide showed promising safety profile in this small phase I study. There were no significant fatigue increases related to Entinostat, but toxicities possibly or probably related to Entinostat or the combination therapy were observed, including anemia and white blood cell decrease.
Article
Oncology
Arun A. Azad, Andrew J. Armstrong, Antonio Alcaraz, Russell Z. Szmulewitz, Daniel P. Petrylak, Jeffrey Holzbeierlein, Arnauld Villers, Boris Alekseev, Taro Iguchi, Neal D. Shore, Francisco Gomez-Veiga, Brad Rosbrook, Ho-Jin Lee, Gabriel P. Haas, Arnulf Stenzl
Summary: In patients with metastatic hormone-sensitive prostate cancer, enzalutamide plus androgen deprivation therapy (ADT) demonstrated overall clinical benefit, regardless of prior local and systemic treatment, disease volume, and risk factors.
PROSTATE CANCER AND PROSTATIC DISEASES
(2022)
Article
Pharmacology & Pharmacy
Yi-Ting Lin, Yen-Chun Huang, Chih-Kuan Liu, Tian-Shyug Lee, Mingchih Chen, Yu-Ning Chien
Summary: Secondary hormone therapy with abiraterone and enzalutamide has significantly improved outcomes for mCRPC patients. Enzalutamide was found to be superior to abiraterone in terms of overall survival, and there was no statistically significant difference in the development of new comorbidities between the two groups. The Charlson comorbidity index score, rather than individual items, was a statistically significant predictor for overall survival.
FRONTIERS IN PHARMACOLOGY
(2021)