Article
Chemistry, Medicinal
Arielle Shkedi, Michael Adkisson, Andrew Schroeder, Walter L. Eckalbar, Szu-Yu Kuo, Leonard Neckers, Jason E. Gestwicki
Summary: By dosing 22Rv1 prostate cancer cells with inhibitors of four proteostasis targets, researchers found additive, synergistic, and antagonistic relationships between the inhibitors. These relationships were associated with activation of stress pathways.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Arielle Shkedi, Isabelle R. Taylor, Frank Echtenkamp, Poornima Ramkumar, Mohamed Alshalalfa, Genesis M. Rivera-Marquez, Michael A. Moses, Hao Shao, Robert Jeffrey Karnes, Len Neckers, Felix Feng, Martin Kampmann, Jason E. Gestwicki
Summary: Castration-resistant prostate cancer (CRPC) is associated with increased reliance on heat shock protein 70 (HSP70) and mitochondrial chaperone protein, HSP60, is selectively required in CRPC cell lines. Knockdown of HSP60 results in loss of mitochondrial spare respiratory capacity and poor survival in prostate cancer patients.
CELL CHEMICAL BIOLOGY
(2022)
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.
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
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
Margherita Corti, Stefano Lorenzetti, Alessandro Ubaldi, Romano Zilli, Daniele Marcoccia
Summary: The role of endocrine disruptors in the human prostate gland is overlooked, but they can influence the homeostasis and diseases of the prostate, including prostate cancer.
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
Genetics & Heredity
Ilker Kiliccioglu, Cenk Y. Bilen, Sinan Sozen, Ece Konac
Summary: The study found that the expressions of AR, AR-V7, and AR-V567es were associated with the stage and Gleason Scores of prostate cancer in Met-PCa patients. Additionally, NF-K beta and HSP-27 protein levels were significantly higher in Met-PCa patients.
Article
Genetics & Heredity
Ilker Kiliccioglu, Cenk Y. Bilen, Sinan Sozen, Ece Konac
Summary: This study investigated the association of AR variants with inflammatory response and regulatory transcriptional activity genes in PCa and Met-PCa patients. The expression levels of AR, AR-V7 and AR-V567es were found to be correlated with prostate cancer stage and Gleason Scores in Met-PCa, while NF-Kβ and HSP-27 protein levels were significantly higher in Met-PCa patients. Targeting proteostasis and inflammation pathways by inhibiting HSP-27 and NF-Kβ could be a valuable strategy to overcome anti-androgen resistance and improve drug therapy in Met-PCa patients with high expression levels of AR-V7 and AR-V567es variants.
Article
Chemistry, Medicinal
Weiguo Xiang, Lijie Zhao, Xin Han, Tianfeng Xu, Steven Kregel, Mi Wang, Bukeyan Miao, Chong Qin, Mingliang Wang, Donna McEachern, Jianfeng Lu, Longchuan Bai, Chao-Yie Yang, Paul D. Kirchhoff, John Takyi-Williams, Lu Wang, Bo Wen, Duxin Sun, Mark Ator, Robert Mckean, Arul M. Chinnaiyan, Shaomeng Wang
Summary: In this study, the highly potent and orally efficacious PROTAC degrader of the androgen receptor (AR), ARD-1676, was discovered and extensively characterized. ARD-1676 effectively induces degradation of clinically relevant AR mutants and inhibits tumor growth in mouse models. It shows great potential as a development candidate for the treatment of AR-positive human prostate cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Andrology
Hui-Yu Dong, Lei Ding, Tian-Ren Zhou, Tao Yan, Jie Li, Chao Liang
Summary: Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.
ASIAN JOURNAL OF ANDROLOGY
(2023)
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
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.
Article
Oncology
Jan Hrudka, Karolina Jelinkova, Hana Fiserova, Radoslav Matej, Vaclav Mandys, Petr Waldauf
Summary: Heat shock proteins (HSPs) are cytoprotective chaperones that play a critical role in maintaining cellular homeostasis. Overexpression of HSPs in cancer cells is associated with shorter overall survival and poorer prognosis. However, only HSP70 expression was found to have a significant impact on colorectal cancer prognosis in this study, with stage dependency.
Review
Biology
Xun Fu, Jiang Liu, Xin Yan, Michael E. DiSanto, Xinhua Zhang
Summary: Prostate cancer is the second most common cancer in aging men globally, but its exact pathogenesis is not fully understood. The heat shock protein (HSP) family plays a significant role in promoting tumor growth and protecting cancer cells from death. HSP molecules are closely involved in important biological processes such as cell differentiation, epithelial-mesenchymal transition, and fibrosis. Agents and inhibitors targeting the critical structure of HSP molecules have been developed for their potent antitumor effects. However, only a small number of them have been clinically tested. Further clinical studies are needed to establish the relationship between HSP70 family, HSP90 molecule, and prostate cancer treatment.