Review
Oncology
Qiao-Hong Chen
Summary: Prostate cancer is a major health concern, and metastatic castration-resistant prostate cancer is the deadliest form. Taxanes, such as docetaxel and cabazitaxel, are the only FDA-approved chemotherapeutics that provide survival benefits for patients with this lethal form of prostate cancer. This review discusses the preclinical and clinical studies, clinical uses, and mechanisms of action of microtubule-stabilizing agents as anti-prostate cancer agents.
Article
Medicine, Research & Experimental
Sue Jin Moon, Byong Chang Jeong, Hwa Jin Kim, Joung Eun Lim, Hye-Jeong Kim, Ghee Young Kwon, Joshua A. Jackman, Jeong Hoon Kim
Summary: The study identified BCT as a potent inhibitor targeting both AR-FL and AR-V7 activities in CRPC, effectively suppressing tumor growth and metastasis. Mechanistically, BCT disrupts the interaction of HSP90 with AR-FL/AR-V7, leading to their degradation and showing promising therapeutic potential against CRPC.
Article
Pharmacology & Pharmacy
Francesca Cavaliere, Pietro Cozzini
Summary: This study used molecular dynamic simulations to reveal the structural effects of R-bicalutamide on the stability of AR homodimers. The results showed that the binding of R-bicalutamide increased the instability of the homodimer, preventing AR migration to the nucleus and transcriptional activity. The W741L mutation resulted in behavior similar to an agonistic system, which may explain the effect of this mutation on drug resistance.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Article
Environmental Sciences
Mark Stanojevic, Marija Sollner Dolenc, Marjan Vracko
Summary: Endocrine-disrupting chemicals (EDCs) are exogenous substances that interfere with the normal function of the human endocrine system. These chemicals can affect specific nuclear receptors, such as androgen receptors (ARs) or estrogen receptors (ERα and ERβ), which play a crucial role in regulating complex physiological processes in humans. It is now more crucial than ever to identify EDCs and reduce exposure to them.
Article
Chemistry, Medicinal
Qian Li, Tao Zhang, Peiran Song, Linjiang Tong, Fang Feng, Jing Guo, Yang Zhou, Hua Xie, Xiaoyun Lu
Summary: A series of novel selective ACK1 inhibitors were developed, and compound 10zi showed potent anti-tumor effect in NSCLC cells and synergistic activity in combination with ASK120067.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
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
Biology
Jacky K. Leung, Yusuke Imamura, Minoru Kato, Jun Wang, Nasrin R. Mawji, Marianne D. Sadar
Summary: The study identifies peptidyl-prolyl isomerase Pin1 targeting the intrinsically disordered N-terminal domain of the androgen receptor (AR). Combining Pin1 inhibition with ralaniten compounds that bind to the AR N-terminal domain enhances antitumor activity on castration-resistant prostate cancer in xenografts, indicating therapeutic potential.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
Carmen Gonzalez-San Segundo, Felipe Counago, Alfonso Gomez-Iturriaga
Summary: This article evaluates the effectiveness and toxicity of adjuvant radiotherapy in high-risk patients after radical prostatectomy, as well as the indications for androgen deprivation therapy, aiming to identify the patient subgroups most likely to benefit from ART. The analysis aims to determine if the evidence now favors early salvage radiotherapy over ART, potentially resolving the controversy surrounding the optimal timing of postoperative radiotherapy.
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
(2021)
Article
Multidisciplinary Sciences
Tatsuya Hosoi, Mitsutaka Yakabe, Hiroko Sasakawa, Takayoshi Sasako, Kohjiro Ueki, Shigeaki Kato, Suzumi M. Tokuoka, Yoshiya Oda, Masahiro Abe, Toshio Matsumoto, Masahiro Akishita, Sumito Ogawa
Summary: Sarcopenia, a type of muscle degeneration, is closely linked to a shift in muscle fiber type. The function of androgen receptor (AR) pathway in sarcopenia is not well understood. In a mouse model, selectively deleting AR in fast-twitch muscle fibers resulted in reduced muscle strength and fatigue resistance, as well as a shift from fast-twitch to slow-twitch fibers. These findings suggest that AR pathway plays a crucial role in muscle composition and function, specifically in fast-twitch fibers.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
News Item
Geosciences, Multidisciplinary
Laura J. Moore, A. Brad Murray
Summary: Sea level rise leads to the migration of barrier islands towards the land. Coastal evolution modeling reveals a lag in island response time lasting for centuries and predicts a 50% increase in migration rates within the next century, even if sea levels stabilize.
Article
Environmental Sciences
Handule Lee, Juyoung Park, Kwangsik Park
Summary: Unlike environmental pollutants, chemicals in consumer products may pose higher risks to human health depending on their usage and interaction. A recent study detected endocrine disrupting chemicals in various consumer products, suggesting a wide range of exposures. The study also found that predictions of mixture activity by appropriate models can support the risk assessment and regulation of these chemicals.
Article
Oncology
Danyang Zhou, Mei Li, Mohamed Hussein Yasin, Qianyi Lu, Jia Fu, Kuikui Jiang, Ruoxi Hong, Shusen Wang, Fei Xu
Summary: This study aimed to investigate the prognostic value of AR in HER2+ nonmetastatic breast invasive ductal carcinoma (IDC) and its relationship with the immune microenvironment. The results showed that AR was closely correlated with overall survival (OS) and had a negative correlation with PD-L1/TILs in HER2+HR- nonmetastatic breast cancer patients.
Article
Oncology
Yuichiro Kanno, Nao Saito, Ryota Saito, Tomohiro Kosuge, Ryota Shizu, Tomofumi Yatsu, Takuomi Hosaka, Kiyomitsu Nemoto, Keisuke Kato, Kouichi Yoshinari
Summary: This study investigated the selective mechanism of selective androgen receptor modulators (SARMs) using the synthetic steroid YK11. The results suggested that gene selective regulation by SARMs is achieved through differential DNA-binding and/or cofactor recruitment by ligands. These findings provide novel insights into the mechanism of action of SARMs.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ao Wang, Yawan Wang, Xin Meng, Yushe Yang
Summary: Prostate cancer is the most common malignancy in men worldwide. In this study, novel thiohydantoin derivatives of enzalutamide were designed and synthesized, with compound 31c identified as a more potent AR antagonist than enzalutamide. The data suggest that 31c could be a promising lead compound for the treatment of prostate cancer.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Engineering, Environmental
Phum Tachachartvanich, Ettayapuram Ramaprasad Azhagiya Singam, Kathleen A. Durkin, J. David Furlow, Martyn T. Smith, Michele A. La Merrill
Summary: Research findings indicate that emerging per- and poly-fluoroalkyl substances (PFASs) may have adverse effects on the human endocrine system and exhibit competitive antiandrogenic effects.
JOURNAL OF HAZARDOUS MATERIALS
(2022)