Review
Biochemistry & Molecular Biology
Haozhe Zhang, Yi Zhou, Zengzhen Xing, Rajiv Kumar Sah, Junqi Hu, Hailiang Hu
Summary: This review discusses the close relationship between the evolution of prostate cancer and androgen levels and the status of the androgen receptor. It also explores how alterations in androgen metabolism contribute to the resistance to anti-androgen therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Tae Jin Kim, Young Hwa Lee, Kyo Chul Koo
Summary: The androgen receptor (AR) plays a crucial role in the development and progression of prostate cancer (PCa), and treatment for hormone-sensitive prostate cancer (HSPC) relies heavily on androgen deprivation therapy (ADT). Despite most patients progressing to castration-resistant prostate cancer (CRPC), studies suggest that manipulating alternative molecular pathways can help improve current treatments and develop novel therapies for CRPC management.
Article
Oncology
Zemin Hou, Shengsong Huang, Zhenfei Li
Summary: Androgens are crucial in the development of prostate cancer, and targeting steroidogenesis and the androgen receptor has been effective in delaying disease progression. New generation androgen receptor pathway inhibitors like abiraterone and enzalutamide continue to emphasize the role of the androgen-AR axis, even in cases of resistance. The importance of this axis in managing the disease after resistance to current treatments, particularly in neuroendocrine prostate cancer, remains uncertain.
Review
Biochemistry & Molecular Biology
Demitria M. Vasilatis, Christopher A. Lucchesi, Paramita M. Ghosh
Summary: Dogs naturally develop prostate cancer similar to aggressive forms found in humans. Prostate cancer samples in dogs often lack androgen receptor (AR), which can enhance our understanding of AR-indifferent prostate cancer in humans. This review highlights the molecular similarities between dog and human prostate cancer variants, suggesting the potential use of dogs as pre-clinical animal models for developing new therapies and diagnostics that can benefit both species.
Article
Cell Biology
Mayao Luo, Yifan Zhang, Zhuofan Xu, Chenwei Wu, Yuedian Ye, Rui Liu, Shidong Lv, Qiang Wei
Summary: The combination therapy of tautomycin and enzalutamide could achieve a more comprehensive inhibition of androgen receptor (AR) signaling in castration-resistant prostate cancer (CRPC). Enzalutamide enhanced tautomycin-induced AR degradation by competing with residual androgens, while tautomycin decreased ARv7 levels through AR degradation. This combination therapy may represent a new therapeutic strategy for CRPC.
CELL DEATH DISCOVERY
(2022)
Editorial Material
Cell Biology
Li Xin
Summary: EZH2 has been shown to promote the development of castration-resistant prostate cancer (CRPC) by interacting with the androgen receptor (AR) to reprogram its transcriptional activity, facilitating the transition of CRPC into a lineage infidelity state.
NATURE CELL BIOLOGY
(2021)
Review
Oncology
Eva Estebanez-Perpina, Charlotte L. Bevan, Iain J. McEwan
Summary: Prostate cancer is the second most common cancer in men globally, with the major clinical problem being castration-resistant prostate cancer (CRPC), where the androgen receptor remains a key therapy target.
Article
Biochemistry & Molecular Biology
Ulrich Sommer, Tiziana Siciliano, Celina Ebersbach, Alicia-Marie K. Beier, Matthias B. Stope, Korinna Joehrens, Gustavo B. Baretton, Angelika Borkowetz, Christian Thomas, Holger H. H. Erb
Summary: PSMA protein plays an important role in the diagnosis and treatment of prostate cancer, and the activation and inhibition of androgen receptor (AR) can affect PSMA protein levels. This study found that AR activation and inhibition affect PSMA protein levels through a possible non-canonical mechanism, and low PSMA expression rates may be necessary to increase PSMA protein through androgen deprivation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Amina Zoubeidi, Paramita M. Ghosh
Summary: The article discusses the 80th anniversary of hormone ablation as a treatment for metastatic prostate cancer, covering the evolution of treatment methods and research progress, including the understanding of the pathobiology of prostate cancer, the development of new treatment paradigms, and treatment resistance and disease progression.
ENDOCRINE-RELATED CANCER
(2021)
Review
Oncology
Samuel R. Denmeade, Laura A. Sena, Hao Wang, Emmanuel S. Antonarakis, Mark C. Markowski
Summary: Inhibition of androgen receptor signaling is the primary treatment for advanced prostate cancer, but eventually leads to resistance. Bipolar androgen therapy (BAT), which involves cycling of supraphysiologic and near-castrate levels of testosterone, disrupts adaptive AR regulation and targets the heterogeneous AR expression in castration-resistant prostate cancer (CRPC). Clinical studies have shown that BAT is safe, improves quality of life, and produces therapeutic responses in approximately 30% of patients. Resistance to BAT is associated with downregulation of AR expression, which interestingly restores sensitivity to subsequent AR inhibitor therapies.
Review
Oncology
Samuel R. Denmeade, Laura A. Sena, Hao Wang, Emmanuel S. Antonarakis, Mark C. Markowski
Summary: Inhibition of androgen receptor (AR) signaling has been the mainstay of treatment for prostate cancer, but resistance to primary and secondary AR-inhibiting therapies is a major challenge. Studies have shown that adaptive upregulation of AR activity and downregulation of AR expression are associated with resistance. Based on these findings, bipolar androgen therapy (BAT) has been developed as a treatment approach to disrupt adaptive AR regulation and target heterogeneous AR expression. Clinical studies have demonstrated that BAT can be safely given to patients with castration-resistant prostate cancer, improving their quality of life and producing therapeutic responses in a significant proportion of patients.
Article
Oncology
Jiaqian Liang, Liyang Wang, Larysa Poluben, Mannan Nouri, Seiji Arai, Lisha Xie, Olga S. Voznesensky, Laura Cato, Xin Yuan, Joshua W. Russo, Henry W. Long, Myles Brown, Shaoyong Chen, Steven P. Balk
Summary: In castration-resistant prostate cancer (CRPC), the splice variant ARv7 can function independently of the full length ARfl, with both contributing independently to overall AR activity.
Article
Oncology
Emuejevoke Olokpa, Sammed N. Mandape, Siddharth Pratap, La Monica Stewart
Summary: The study used RNA sequencing to identify the signaling pathways regulated by metformin in androgen-receptor positive, castration-resistant prostate cancer cells. Metformin was found to alter the expression of genes involved in metabolic pathways, the spliceosome, RNA transport, and protein processing within the endoplasmic reticulum, as well as in ErbB, insulin, mTOR, TGF-beta, MAPK, and Wnt signaling pathways. Some of the metformin-regulated genes are known to be direct transcriptional targets of p53 or AR, and metformin-induced reductions in AR mRNA and protein levels contributed to these alterations in gene expression.
Article
Biochemistry & Molecular Biology
Ibrahim M. Atawia, Prem P. Kushwaha, Shiv Verma, Spencer Lin, Eswar Shankar, Osama Abdel-Gawad, Sanjay Gupta
Summary: Abiraterone acetate has been approved for the treatment of advanced-stage prostate cancer, but almost all patients develop therapeutic resistance and disease recurrence. In this study, co-treatment of abiraterone and ICG001 was shown to overcome resistance and inhibit stem cell markers and cellular proliferation in prostate cancer cells.
MOLECULAR CARCINOGENESIS
(2023)
Article
Oncology
Anmbreen Jamroze, Gurkamal Chatta, Dean G. Tang
Summary: This article discusses how AR heterogeneity affects the response of prostate cancer to treatment, emphasizing the de novo resistance to ARSIs exhibited by AR-/lo PCa cells/clones. Several potential combinatorial strategies are proposed, such as combining ARSIs with stem cell targeting therapeutics, to co-target both AR+ and AR-/lo PCa cells and metastatic clones.
Article
Oncology
Hao Tian, Fu-ju Chou, Jing Tian, Yong Zhang, Bosen You, Chi-Ping Huang, Shuyuan Yeh, Yuanjie Niu, Chawnshang Chang
Summary: ASC-J9 (R) can suppress prostate cancer progression via an androgen receptor-independent mechanism by altering ATF3 expression, leading to decreased PTK2 expression. Clinical and preclinical studies support the role of ATF3/PTK2 signaling in PCa progression.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Cell Biology
Zhendong Xiang, Yin Sun, Bosen You, Meng Zhang, Chiping Huang, Junfeng Yu, Xiangyun You, Denglong Wu, Chawnshang Chang
Summary: The study found that Enzalutamide-resistant prostate cancer cells can be suppressed by high doses of the androgen DHT. Targeting the BCL-XL protein can enhance the inhibitory effect of high-dose DHT on cell growth, promoting cell death.
CELL DEATH & DISEASE
(2021)
Article
Urology & Nephrology
Yoshihide Kawasaki, Shigeto Ishidoya, Ryo Morimoto, Yoshikiyo Ono, Kei Omata, Yuta Tezuka, Naoki Kawamorita, Shinichi Yamashita, Koji Mitsuzuka, Fumitoshi Satoh, Akihiro Ito
Summary: Middle-aged patients with primary aldosteronism (PA) who undergo laparoscopic adrenalectomy (LADX) may experience limited antihypertensive effects, particularly in older patients. However, LADX can lead to significant improvements in mental health-related quality of life (HRQoL) in older patients, despite lower rates of antihypertensive drug use post-surgery.
UROLOGIA INTERNATIONALIS
(2023)
Article
Oncology
Kento Morozumi, Yoshihide Kawasaki, Masamitsu Maekawa, Shinya Takasaki, Tomonori Sato, Shuichi Shimada, Naoki Kawamorita, Shinichi Yamashita, Koji Mitsuzuka, Nariyasu Mano, Akihiro Ito
Summary: This study identified potential biomarkers for predicting postoperative recurrence of RCC through precise quantitative analysis of urinary metabolites. A logistic regression analysis identified five metabolites to build a recurrence prediction model. The high-risk group showed a significant drop in recurrence-free survival rates, and in vitro studies revealed higher metabolite concentrations in metastatic tumor cell lines.
Article
Cell Biology
Kuo-Chung Lan, Kuo-Ting Wei, Pei-Wen Lin, Ching-Chen Lin, Pei-Ling Won, Ya-Fen Liu, Yun-Ju Chen, Bi-Hua Cheng, Tien-Min G. Chu, Jia-Feng Chen, Ko-En Huang, Chawnshang Chang, Hong-Yo Kang
Summary: The study found that androgen receptor (AR) is highly expressed in periosteum cells during bone fracture repair and is co-localized with a mesenchymal progenitor cell marker, Prrx1. Mice lacking AR in periosteum showed reduced callus size and new bone volume. Targeting the androgen/AR axis in periosteum may provide a novel therapy approach to improve fracture healing.
CELL DEATH & DISEASE
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Eri Ota, Naoko Mori, Shinichi Yamashita, Shunji Mugikura, Akihiro Ito, Kei Takase
Summary: This study found that the ADC parameters at the second MRI and the changes in ADC parameters from baseline to the second MRI may be effective factors in distinguishing between PRIAS non-reclassification and reclassification groups during active surveillance of prostate cancer.
ABDOMINAL RADIOLOGY
(2022)
Article
Oncology
Hiromichi Iwamura, Kei Mizuno, Shusuke Akamatsu, Shingo Hatakeyama, Yuki Tobisawa, Shintaro Narita, Takuma Narita, Shinichi Yamashita, Sadafumi Kawamura, Toshihiko Sakurai, Naoki Fujita, Hirotake Kodama, Daisuke Noro, Ikuko Kakizaki, Shigeyuki Nakaji, Ken Itoh, Norihiko Tsuchiya, Akihiro Ito, Tomonori Habuchi, Chikara Ohyama, Tohru Yoneyama
Summary: The study aimed to establish a urological disease-specific scoring system using machine learning (ML) approach and Ig N-glycan signatures. The results showed that the scoring system was able to effectively discriminate different urological diseases and had good diagnostic ability.
Article
Urology & Nephrology
Takashi Kawahara, Koji Kawai, Takahiro Kojima, Yoshiyuki Nagumo, Shotarou Sakka, Shuya Kandori, Hiromitsu Negoro, Bryan J. Mathis, Kazushi Maruo, Koji Miura, Noriaki Sakamoto, Nobuo Shinohara, Shinichi Yamashita, Kan Yonemori, Takeshi Kishida, Osamu Ukimura, Kazuo Nishimura, Yasuyuki Kobayashi, Hiroyuki Nishiyama
Summary: This phase II study evaluated the efficacy and safety of nivolumab for relapsed germ cell tumor. The results showed that tumor mutation burden may be a potential biomarker for assessing the response of germ cell tumors.
INTERNATIONAL JOURNAL OF UROLOGY
(2022)
Article
Oncology
Jie Ding, Xin-Gang Cui, Hao-Jie Chen, Yin Sun, Wei-Wei Yu, Jie Luo, Guang-Qian Xiao, Chawnshang Chang, Jun Qi, Shuyuan Yeh
Summary: Vasculogenic mimicry (VM), an alternative channel for tumor nutrient supply, is associated with poor prognosis in renal cell carcinoma (RCC). Sunitinib, a tyrosine kinase inhibitor (TKI), has been reported to induce VM formation by up-regulating estrogen receptor beta (ERβ) expression. This study showed that treatment with sunitinib and another TKI, axitinib, also induced ERβ expression in RCC cell lines. Clinical RCC patients with higher ERβ expression were more likely to have VM. Mechanistically, TKI-induced ERβ up-regulated the circular RNA DGKD, which enhanced VM formation by increasing VE-cadherin expression. Targeting circDGKD intercepted sunitinib-induced RCC VM formation and improved survival in an animal model.
Article
Cell Biology
Lei Chen, Yin Sun, Min Tang, Denglong Wu, Zhendong Xiang, Chi-Ping Huang, Bosen You, Dongdong Xie, Qinglin Ye, Dexin Yu, Chawnshang Chang
Summary: This study found that high-dose androgens can suppress the growth of Enzalutamide-resistant (EnzR) castration-resistant prostate cancer (CRPC) cells. The mechanism involves the transcriptional regulation of the circRNA-BCL2 host gene BCL2, which in turn affects the expression of miRNA-198 and modulates the expression of AMBRA1. This leads to the induction of autophagic cell death and the suppression of EnzR CRPC cell growth.
CELL DEATH DISCOVERY
(2022)
Article
Cell Biology
Yang Yang, Jindong Sheng, Shuai Hu, Yun Cui, Jing Xiao, Wei Yu, Jing Peng, Wenke Han, Qun He, Yu Fan, Yuanjie Niu, Jun Lin, Ye Tian, Chawnshang Chang, Shuyuan Yeh, Jie Jin
Summary: This study identified the histopathological characteristics and molecular mechanisms underlying accelerated progression of benign prostatic hyperplasia (BPH). Increased stromal components and prostatic fibrosis, accompanied by higher myofibroblast accumulation and collagen deposition, were found to be the main features of accelerated progressive BPH tissues. Mechanism dissection revealed that higher expression of CYP19 and G protein-coupled estrogen receptor (GPER) with higher estrogen biosynthesis contribute to the progression of BPH. Targeting the CYP19/estrogen/GPER/G alpha i signaling axis may provide new personalized therapeutics for better suppressing the progression of BPH.
CELL DEATH & DISEASE
(2022)
Article
Medicine, General & Internal
Daigo Chiba, Yoshihide Kawasaki, Atsushi Miyagi, Yuki Katsumata, Yohei Satake, Shuichi Shimada, Hiromichi Katayama, Naoki Kawamorita, Shinichi Yamashita, Koji Mitsuzuka, Kanae Akita, Mika Watanabe, Akihiro Ito
Summary: This case study describes a 74-year-old male patient with left renal cancer lymph node metastasis and idiopathic multicentric Castleman disease (CD). The patient died due to uncontrollable renal cancer and poor improvement in the inflammatory response. It is important to exclude malignant tumors in the treatment of idiopathic multicentric CD.
TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Oncology
Naomi Sato, Kazue Ise, Shuko Hata, Shinichi Yamashita, Akihiro Ito, Hironobu Sasano, Yasuhiro Nakamura
Summary: The study found that the loss of steroid sulfatase and aromatase in urinary bladder carcinoma is significantly correlated with advanced stages of the cancer, and estrogen sulfotransferase and aromatase are also correlated with the nuclear grade of the carcinoma. Biologically active estrogens binding to estrogen receptors can suppress tumor progression, while inactive estrogens may promote progression of the disease, suggesting the potential clinical utility of selective estrogen receptor modulators (SERMs) in treating urinary bladder carcinoma patients.
PATHOLOGY & ONCOLOGY RESEARCH
(2021)
Article
Urology & Nephrology
Shinichi Yamashita, Yoshimi Suzukamo, Kenichi Kakimoto, Motohide Uemura, Takeshi Kishida, Koji Kawai, Terukazu Nakamura, Takayuki Goto, Takahiro Osawa, Shigeyuki Yamada, Kazuo Nishimura, Norio Nonomura, Hiroyuki Nishiyama, Takumi Shiraishi, Osamu Ukimura, Osamu Ogawa, Nobuo Shinohara, Akihiro Ito, Yoichi Arai
Summary: The study aimed to validate the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 in Japanese-speaking testicular cancer survivors. Results showed that the psychometric properties of the Japanese version were equivalent to the original version, indicating its usefulness in assessing the health-related quality of life of testicular cancer patients.
INTERNATIONAL JOURNAL OF UROLOGY
(2021)
Article
Urology & Nephrology
Juntaro Koyama, Shinichi Yamashita, Shigeyuki Yamada, Shinji Fujii, Takuro Goto, Hiromichi Katayama, Yohei Satake, Takuma Sato, Shuichi Shimada, Yoshihide Kawasaki, Naoki Kawamorita, Koji Mitsuzuka, Yoichi Arai, Akihiro Ito
Summary: The study showed that 44% of testicular cancer survivors who received chemotherapy and retroperitoneal lymph node dissection developed ejaculation disorders after treatment. Ejaculation disorders had a significant negative impact on sexual life.
INTERNATIONAL JOURNAL OF UROLOGY
(2021)