Review
Biochemistry & Molecular Biology
Xia Deng, Chenxi Wang, Yue Xia, Guoyue Yuan
Summary: Protein phosphorylation and dephosphorylation play crucial roles in cell function regulation, especially in the regulation of liver glucose and lipid metabolism. PTG, a protein phosphatase, serves as an important regulator in glucose and lipid metabolism.
Article
Oncology
E. C. de Heer, C. E. Zois, E. Bridges, B. van der Vegt, H. Sheldon, W. A. Veldman, M. C. Zwager, T. van der Sluis, S. Haider, T. Morita, O. Baba, C. P. Schroder, S. de Jong, A. L. Harris, M. Jalving
Summary: The study found that the gene GYS1 is related to tumor growth and therapy resistance in breast cancer, especially in triple-negative breast cancer. Inhibiting GYS1 weakens the proliferation ability of breast cancer cells and makes them more sensitive to inhibition of mitochondrial proteostasis.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Nadine Abdel Hadi, Gabriela Reyes-Castellanos, Alice Carrier
Summary: Cell metabolism in cancer cells is reprogrammed to meet their high energy and biosynthetic demands, leading to alterations in redox metabolism and accumulation of reactive oxygen species (ROS). Cancer cells adapt to high ROS levels, contributing to tumorigenesis, metastasis, therapy resistance, and relapse. Combining strategies to increase ROS production and inhibit antioxidant capacity is a promising approach for pancreatic cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Medicine, Research & Experimental
Michael Morales, Xiang Xue
Summary: Iron is crucial for cellular functions and human health, but excess iron can lead to oxidative DNA damage and cancer. Cancer cells are more dependent on iron than normal cells, making targeting iron metabolism in cancer cells an emerging and powerful therapeutic strategy.
Review
Biochemistry & Molecular Biology
Joanna Kubik, Ewelina Humeniuk, Grzegorz Adamczuk, Barbara Madej-Czerwonka, Agnieszka Korga-Plewko
Summary: Cancer, the second leading cause of global death, necessitates the development of new treatment strategies that are highly effective and have few side effects. This review presents the changes in metabolic pathways in cancer cells and highlights the differences in metabolic phenotype between cancer cells and normal cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Zhen-duo Shi, Lin Hao, Xiao-xiao Han, Zhuo-Xun Wu, Kun Pang, Yang Dong, Jia-xin Qin, Guang-yue Wang, Xuan-ming Zhang, Tian Xia, Qing Liang, Yan Zhao, Rui Li, Shao-qi Zhang, Jun-hao Zhang, Jian-gang Chen, Gong-cheng Wang, Zhe-Sheng Chen, Cong-hui Han
Summary: This study found that the expression of the HNRNPU gene is associated with cisplatin sensitivity in bladder urothelial carcinoma cells. Inhibition of HNRNPU may have potential therapeutic effects for cisplatin-resistant bladder cancer.
Review
Oncology
Kexin Fan, Zhan Liu, Min Gao, Kangsheng Tu, Qiuran Xu, Yilei Zhang
Summary: Metabolic reprogramming is a hallmark of tumors, and the dependency of tumor cells on specific nutrients can be exploited for cancer treatment. This review discusses the mechanisms and applications of nutrient dependency, as well as the strategies and challenges in targeting nutrient dependency in different types of cancer.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Daryl Thompson, Nathan Lawrentschuk, Damien Bolton
Summary: Epigenetic changes are common in urological cancers and have potential as targets for cancer therapy. There have been 25 clinical trials investigating targeted epigenetic therapy in bladder cancer, but no phase 3 trials have been conducted so far. Epigenetics is a rapidly advancing field and holds great promise for the treatment of bladder cancer.
Review
Biochemistry & Molecular Biology
Kenza Mamouni, Georgios Kallifatidis, Bal L. Lokeshwar
Summary: Metabolic reprogramming is a hallmark of malignancy, with recent studies showing that tumor cells depend on both the Warburg effect and mitochondrial metabolism for survival. Targeting mitochondria in cancer cells is an attractive therapeutic strategy, but the metabolic flexibility of cancer cells may lead to resistance mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sheng-Yen Hsiao, Chih-Hsin Tang, Po-Chun Chen, Tien-Huang Lin, Chia-Chia Chao
Summary: Melatonin exhibits antitumor activities against bladder cancer by inhibiting the epithelial-mesenchymal transition process and autophagy of bladder cancer cells. Melatonin treatment also slightly prolongs the survival of tumor-bearing mice.
Article
Biochemistry & Molecular Biology
Sebastien Rinaldetti, Qiong Zhou, Joshua M. Abbott, Florus C. de Jong, Hector Esquer, James C. Costello, Dan Theodorescu, Daniel LaBarbera
Summary: This study discovered novel subtype-stratified therapy approaches for bladder cancer based on high-content screening, and correlated drug sensitivity with functional genomics to validate and understand the underlying mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Qi-Chao Yang, Shuo Wang, Yuan-Tong Liu, An Song, Zhi-Zhong Wu, Shu-Cheng Wan, Hui-Min Li, Zhi-Jun Sun
Summary: PCSK9 expression is upregulated in HNSCC tissues and higher expression is associated with poorer prognosis. Inhibition of PCSK9 suppresses cancer cell stemness via LDLR-dependent mechanism. PCSK9 inhibition enhances CD8(+) T cell infiltration, reduces MDSCs, and improves the efficacy of anti-PD-1 ICB therapy in HNSCC.
Review
Oncology
Josep Tarrago-Celada, Marta Cascante
Summary: The search for new therapeutic opportunities to target cancer metastasis is crucial for the improvement of cancer treatment. Metabolic adaptation is an important hallmark of cancer and metastasis, and targeting metabolic pathways represents a promising strategy to specifically target metastatic cells, especially in colorectal cancer metastasis. Expanding research in this field may lead to the development of new therapeutic strategies for metastatic colorectal cancer.
Review
Medicine, Research & Experimental
Tobias Achu Muluh, Xing-sheng Shu, Ying Ying
Summary: Cancer metabolism is the unique utilization of nutrients and energy by cancer cells to support their growth and proliferation. This metabolic profile is characterized by an increased reliance on glucose and glutamine as energy sources and changes in key metabolic intermediates. The study of cancer metabolism aims to understand these metabolic changes and identify potential therapeutic targets for cancer treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Kang Wu, Jun Zeng, Xulian Shi, Jiajia Xie, Yuqing Li, Haoxiang Zheng, Guoyu Peng, Guanghui Zhu, Dongdong Tang, Song Wu
Summary: The study identified a subset of Treg cells with high expression of TIGIT and IL-32 using single-cell sequencing. This subset of Treg cells suppressed the antitumor immune response and promoted bladder cancer metastasis. However, targeting TIGIT reversed immunosuppression, inhibited IL-32 secretion, and suppressed bladder cancer cell metastasis.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Jin-Fen Xiao, Ley-Fang Kua, Ling-Wen Ding, Qiao-Yang Sun, Khine Nyein Myint, Xiu-Rong Chia, Nachiyappan Venkatachalam, Xinyi Loh, Jason E. Duex, Vanessa Neang, Siqin Zhou, Ying Li, Henry Yang, H. Phillip Koeffler, Dan Theodorescu
Summary: KDM6A depletion promotes cell migration and transformation in breast cells, reduces sensitivity to therapeutic agents, induces TGF beta secretion, and suppresses cytotoxic gene expression. KDM6A deficiency and TGF beta treatment drive tumor progression, leading to disorganized acinar structures and expression profiles associated with epithelial-to-mesenchymal transition and metastasis.
MOLECULAR CANCER RESEARCH
(2022)
Editorial Material
Urology & Nephrology
Dan Theodorescu, Zihai Li, Xue Li
Summary: When studying the disparities in incidence and mortality rates between males and females in diseases like bladder cancer, it is important to design experiments properly and recognize that sex and gender are not interchangeable concepts. Understanding the roles of sex and gender in disease is essential for addressing these disparities effectively.
NATURE REVIEWS UROLOGY
(2022)
Article
Oncology
Sungyong You, Minhyung Kim, Steven Widen, Alexander Yu, Gloria C. Galvan, Yunhee Choi-Kuaea, Eduardo J. Eyzaguirre, Lars Dyrskjot, David J. McConkey, Woonyoung Choi, Dan Theodorescu, Keith S. Chan, Yong Shan, Douglas S. Tyler, Amanda M. De Hoedt, Stephen J. Freedland, Stephen B. Williams
Summary: This study aimed to compare the subtype distribution and differentially expressed genes between African Americans (AAs) and European Americans (EAs) in patients with high-risk nonmuscle-invasive bladder cancer (NMIBC). The results showed differences in gene expression between AAs and EAs, suggesting potential race-based etiologies for muscle invasion, response to treatments, and transcriptome pathway regulations.
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
(2022)
Article
Multidisciplinary Sciences
Fotis Nikolos, Kazukuni Hayashi, Xen Ping Hoi, Mark Ellie Alonzo, Qianxing Mo, Armine Kasabyan, Hideki Furuya, Jane Trepel, Dolores Di Vizio, Jlenia Guarnerio, Dan Theodorescu, Charles Rosser, Andrea Apolo, Matthew Galsky, Keith Syson Chan
Summary: Chemoimmunotherapy has shown limited clinical benefit in bladder cancer patients and the reasons for this are not well understood. This study reveals that platinum-based chemotherapy hinders the infiltration and activity of CD8+ T cells in mouse models of muscle-invasive bladder cancer. The release of prostaglandin E-2 (PGE(2)) from dying cancer cells is identified as a mechanism that inhibits dendritic cell maturation. By blocking PGE(2) release, CD8+ T cells regain their tumoricidal activity and infiltrate the tumor site. Blocking PGE(2) release synergizes with chemotherapy and enhances the response to immune checkpoint inhibitor therapy. These findings highlight the potential of targeting the COX-2/PGE2 axis in chemoimmunotherapy for bladder cancer.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Yang Zhang, Fan Huo, Qiang Cao, Ru Jia, Qiju Huang, Zhu A. Wang, Dan Theodorescu, Qiang Lv, Pengchao Li, Chao Yan
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Sungyong You, Minhyung Kim, Xen Ping Hoi, Yu Cheng Lee, Li Wang, David Spetzler, Jim Abraham, Dan Magee, Prerna Jain, Matthew D. Galsky, Keith Syson Chan, Dan Theodorescu
Summary: The study found that gene signature scores driven by DDR1 and DDR2 can predict the response to anti-PD-1 therapy.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Review
Urology & Nephrology
Michael Nazmifar, Cheyenne Williams, Aurash Naser-Tavakolian, John Heard, Charles Rosser, Dan Theodorescu, Michael Ahdoot
Summary: The purpose of this study is to evaluate the efficacy of various therapeutic agents for high-grade nonmuscle-invasive bladder cancer following failed bacillus Calmette-Guerin treatment. A systematic review of available clinical trials was conducted, and a total of 70 studies evaluating 27 treatment options were analyzed. Intravesical chemotherapy and hyperthermia paired with chemotherapy demonstrated high complete response rates, while immunotherapy and novel agents also showed promising results. The treatments had low toxicity profiles and complication rates.
JOURNAL OF UROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Christian Soehngen, David J. Thomas, Margaretha A. Skowron, Felix Bremmer, Markus Eckstein, Anja Stefanski, Marc D. Driessen, Gamal A. Wakileh, Kai Stuehler, Peter Altevogt, Dan Theodorescu, Ruediger Klapdor, Axel Schambach, Daniel Nettersheim
Summary: This study aimed to understand the molecular function of CD24 in vitro and evaluate the cytotoxic capacity of NK cell CAR against CD24 in urological tumor cells. The results showed that CD24 interacts with proteins involved in cell adhesion, ATP binding, phosphoprotein binding, and post-translational modifications. Treatment with NK-CD24-CAR cells significantly decreased cell viability and induced apoptosis specifically in CD24(+) tumor cells. This study provides a promising novel target for immune therapeutic approaches against urological malignancies.
Article
Multidisciplinary Sciences
Hany A. Abdel-Hafiz, Johanna M. Schafer, Xingyu Chen, Tong Xiao, Timothy D. Gauntner, Zihai Li, Dan Theodorescu
Summary: Loss of the Y chromosome (LOY) correlates with poor prognoses in bladder cancer patients. LOY mutations alter T cell function, promoting T cell exhaustion and sensitizing them to PD-1-targeted immunotherapy.
Article
Cell Biology
Florus C. de Jong, Teemu D. Laajala, Robert F. Hoedemaeker, Kimberley R. Jordan, Angelique C. J. van der Made, Egbert R. Boeve, Deric K. E. van der Schoot, Bart Nieuwkamer, Emiel A. M. Janssen, Tokameh Mahmoudi, Joost L. Boormans, Dan Theodorescu, James C. Costello, Tahlita C. M. Zuiverloon
Summary: The recommended treatment for high-risk non-muscle-invasive bladder cancer patients is tumor resection followed by adjuvant Bacillus Calmette-Guerin (BCG) bladder instillations. However, only 50% of patients benefit from this therapy. Identifying tumors unlikely to respond to BCG can lead to alternative treatments for these patients.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Review
Oncology
Peris R. Castaneda, Dan Theodorescu, Charles J. Rosser, Michael Ahdoot
Summary: Bladder cancer is a complex disease with variable prognosis, and recent studies have identified frequent genetic alterations and molecular subtypes. Personalized treatment strategies and the development of biomarkers to predict response and guide therapy in bladder cancer have become a focus of research. In this review, we summarize the latest studies on novel biomarkers in bladder cancer, specifically those intended to improve risk stratification and treatment selection, based on a search of recently published PubMed articles using relevant keywords.
FRONTIERS IN ONCOLOGY
(2023)
Article
Urology & Nephrology
Thomas W. Flaig, Catherine M. Tangen, Siamak Daneshmand, Ajjai Shivaram Alva, M. Scott Lucia, David James McConkey, Dan Theodorescu, Amir Goldkorn, Matthew I. Milowsky, Rick Bangs, Gary R. MacVicar, Bruno R. Bastos, Jared S. Fowles, Daniel L. Gustafson, Melissa Plets, Ian M. Thompson Jr, Seth P. Lerner
Summary: This article mainly evaluated the predictive role of the COXEN gene expression model in neoadjuvant chemotherapy for bladder cancer, and conducted a secondary analysis of the association between COXEN scores and event-free survival and overall survival.
Review
Medicine, General & Internal
Lars Dyrskjot, Donna E. Hansel, Jason A. Efstathiou, Margaret A. Knowles, Matthew D. Galsky, Jeremy Teoh, Dan Theodorescu
Summary: Bladder cancer is a global health issue with distinct molecular subtypes and pathogenic pathways. Early detection and diagnosis are crucial for improving patient outcomes. Treatment options vary depending on the invasion level and include surgery and immunotherapy. Effective management requires a multidisciplinary approach that considers patient characteristics and molecular disease characteristics.
NATURE REVIEWS DISEASE PRIMERS
(2023)
Article
Multidisciplinary Sciences
Hany A. Abdel-Hafiz, Saravana Kumar Kailasam Mani, Wesley Huang, I. I. I. Kenneth H. Gouin, Yuzhou Chang, Tong Xiao, Qin Ma, Zihai Li, Simon R. V. Knott, Dan Theodorescu
Summary: In this study, single-cell RNA sequencing was used to characterize cell-type specific transcriptional differences between male and female BBN-induced tumors. Proportional and gene expression differences were found in epithelial and non-epithelial subpopulations between male and female tumors. Several genes were found to predict sex-specific survival in human BLCA datasets. Novel and clinically relevant sex-specific transcriptional signatures were identified, including immune cells in the tumor microenvironment. It validated the relevance of the BBN model for studying sex differences in human BLCA.
Review
Urology & Nephrology
Jun Gong, Daniel M. Kim, Michael R. Freeman, Hyung Kim, Leigh Ellis, Bethany Smith, Dan Theodorescu, Edwin Posadas, Robert Figlin, Neil Bhowmick, Stephen J. Freedland
Summary: Black men with prostate cancer have biologically distinct cancers compared to white men, including genetic alterations, protein differences, and tumor microenvironment. Socioeconomic status partially explains the disparities, but not completely. Further research on these biological differences can guide efforts to improve treatment outcomes for Black men.
NATURE REVIEWS UROLOGY
(2023)