Review
Biochemistry & Molecular Biology
Rahul Advani, Sara Luzzi, Emma Scott, Caroline Dalgliesh, Joachim Weischenfeldt, Jennifer Munkley, David J. Elliott
Summary: This article discusses the expression of splicing regulators ESRP1 and ESRP2 in aggressively proliferating primary prostate tumors as markers of disease progression. It suggests that ESRP1 and ESRP2 act as lineage survival oncogenes in prostate cancer and highlights the need to identify the gene expression targets controlled by these regulators to develop targeted therapies.
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
Pharmacology & Pharmacy
Yun-Ho Choi, Jaeyoon Kim, Jae Young Shin, Nae-Gyu Kang, Sanghwa Lee
Summary: This study investigated the antiandrogenic effects of FMN in prostate cancer cells. FMN inhibited androgen receptor protein expression, decreased PSA level, and downregulated androgen regulated genes. FMN bound to androgen receptor and regulated androgen receptor signaling through the PI3K-AktMDM2 pathway.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Haitham A. Elmarakeby, Justin Hwang, Rand Arafeh, Jett Crowdis, Sydney Gang, David Liu, Saud H. AlDubayan, Keyan Salari, Steven Kregel, Camden Richter, Taylor E. Arnoff, Jihye Park, William C. Hahn, Eliezer M. Van Allen
Summary: The development of a biologically informed deep learning model P-NET enables stratification of prostate cancer patients by treatment-resistance state and evaluation of molecular drivers of treatment resistance for therapeutic targeting with complete model interpretability. This approach shows superior performance in cancer state prediction using molecular data compared to other modeling approaches.
Article
Chemistry, Medicinal
David M. Carter, Edgar Specker, Piotr H. Malecki, Jessica Przygodda, Krystyna Dudaniec, Manfred S. Weiss, Udo Heinemann, Marc Nazare, Ulrich Gohlke
Summary: A benzyl-substituted variant of an inhibitor targeting KDM4 enzymes demonstrates improved potency, cell-permeability, and cytotoxicity against prostate cancer cells. The inhibition mechanism involves competition with Fe2+ at the active site and binding to a distal site on the enzyme surface. The inhibitor's cytostatic effect is attributed to direct intracellular inhibition of KDM4 enzymes, leading to altered gene expression and epigenetic changes in PCa cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Environmental Sciences
Vipendra Kumar Singh, Rajesh Pal, Priyansh Srivastava, Gauri Misra, Yogeshwer Shukla, Pradeep Kumar Sharma
Summary: The study found that some common environmental endocrine disrupting chemicals have androgen mimicking potential, affecting androgen-dependent prostate cancer cells, and may regulate the development and growth of prostate cancer by modulating proliferation in androgen-sensitive cells and epigenetic machinery.
ENVIRONMENTAL POLLUTION
(2021)
Review
Endocrinology & Metabolism
Bharti Jaiswal, Akanksha Agarwal, Ashish Gupta
Summary: This review summarizes recent research advances in understanding the role of lysine acetyltransferases (KATs) in regulating androgen receptor (AR) activity at the level of post-translational modifications in normal prostate physiology and prostate cancer (PCa) development. Targeting these enzymes may have therapeutic potential for AR-related pathology in combination with hormonal therapy.
FRONTIERS IN ENDOCRINOLOGY
(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)
Article
Chemistry, Multidisciplinary
Yohei Saito, Atsushi Mizokami, Sayaka Maeda, Kyoko Takahashi, Kouji Izumi, Masuo Goto, Kyoko Nakagawa-Goto
Summary: Newly synthesized bi-naphthyl derivatives 2 and 3 exhibited stronger inhibitory effects on androgen-independent prostate cancer cell lines compared to the parent molecule, showing potential as lead compounds for cancer treatment.
Article
Chemistry, Medicinal
Fei-Fei Yang, Xue-Li Xu, Ting Hu, Jian-Quan Liu, Jin-Zhu Zhou, Li-Ying Ma, Hong-Min Liu
Summary: Chemotherapy, targeted therapy, and immunotherapy can effectively treat most tumors, but drug resistance limits their success. Lysine-specific demethylase 1 (LSD1) plays a role in regulating tumor cell invasion, metastasis, apoptosis, and immune evasion, which are associated with tumor development and progression. Recent studies have found that LSD1 inhibition can restore sensitivity of tumor cells to anticancer drugs containing immune checkpoint inhibitors (ICIs) through various pathways. This review discusses the role of LSD1 in cancer drug resistance and explores the potential of using LSD1 inhibitors in combination with other agents to overcome resistance.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Swapnil Ganesh Sanmukh, Nilton Jose Dos Santos, Caroline Nascimento Barquilha, Marcio De Carvalho, Patricia Pintor Dos Reis, Flavia Karina Delella, Hernandes F. F. Carvalho, Dorota Latek, Tamas Feher, Sergio Luis Felisbino
Summary: Bacteriophages have shown effective counteraction against bacterial infections and potential as a therapy for cancer. In this study, the bacteriophage MS2 was found to influence the expression of genes related to proliferation and survival in LNCaP prostate epithelial cells. The exposure of LNCaP cells to MS2 resulted in changes in cell viability and gene expression, with a temporary reduction in viability and significant upregulation of specific genes associated with normal cellular processes and tumor progression. This study suggests that MS2 impairs LNCaP cells by reducing anchorage-dependent survival and altering androgen signaling, potentially through a caveolin-mediated endocytosis mechanism.
Review
Integrative & Complementary Medicine
Li Zhong-Rui, Gu Meng-Zhen, Xu Xiao, Zhang Jing-Han, Zhang Hai-Li, Han Chao
Summary: This review highlights recent advances in natural LSD1 inhibitors, including their discovery and identification process, natural sources, chemical structures, anticancer effects, and structure-activity relationships. Natural products play an important role in drug discovery, particularly in cancer therapy.
CHINESE JOURNAL OF NATURAL MEDICINES
(2022)
Article
Oncology
Beshara Sheehan, Antje Neeb, Lorenzo Buroni, Alec Paschalis, Ruth Riisnaes, Bora Gurel, Veronica Gil, Susana Miranda, Mateus Crespo, Christina Guo, Juan Jimenez Vacas, Ines Figueiredo, Ana Ferreira, Jon Welti, Wei Yuan, Suzanne Carreira, Adam Sharp, Johann de Bono
Summary: This study found that anticancer treatment-induced double-strand DNA damage can upregulate PSMA protein expression, providing support for exploring rational combinations to maximize the antitumor activity of PSMA-targeted therapeutic strategies by upregulating PSMA.
CLINICAL CANCER RESEARCH
(2022)