Review
Pharmacology & Pharmacy
Raef Shams, Yoshihiro Ito, Hideyuki Miyatake
Summary: mTOR is a protein kinase involved in cell growth and proliferation, which can be assembled into mTORC1 and mTORC2 complexes with different functions. In cancer cells, mTOR is hyperactivated to adapt to stress conditions, leading to efforts in developing compounds to inhibit mTOR and disrupt cancer cell metabolism.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Oncology
Aleksandra Derwich, Monika Sykutera, Barbara Brominska, Miroslaw Andrusiewicz, Marek Ruchala, Nadia Sawicka-Gutaj
Summary: This review investigates the expression of mTOR gene and protein in papillary thyroid cancer (PTC) and their relationship with PTC risk and clinical outcome. It also reviews the use of mTOR inhibitors and potential targeted therapies in PTC. The results of previous studies are summarized, and future research directions are suggested.
Review
Oncology
Tatiana Shorstova, William D. Foulkes, Michael Witcher
Summary: Transcriptional upregulation of oncogenes drives tumor progression, and targeting BET proteins with inhibitors has shown promise in suppressing oncogenic networks in tumors. Understanding the biology of BET proteins, designing better BET inhibitors, and incorporating BET inhibitors into combination therapies can enhance their efficacy in clinical settings.
BRITISH JOURNAL OF CANCER
(2021)
Review
Biochemistry & Molecular Biology
Antonino Glaviano, Aaron S. C. Foo, Hiu Y. Lam, Kenneth C. H. Yap, William Jacot, Robert H. Jones, Huiyan Eng, Madhumathy G. Nair, Pooyan Makvandi, Birgit Geoerger, Matthew H. Kulke, Richard D. Baird, Jyothi S. Prabhu, Daniela Carbone, Camilla Pecoraro, Daniel B. L. Teh, Gautam Sethi, Vincenzo Cavalieri, Kevin H. Lin, Nathalie R. Javidi-Sharifi, Eneda Toska, Matthew S. Davids, Jennifer R. Brown, Patrizia Diana, Justin Stebbing, David A. Fruman, Alan P. Kumar
Summary: The PI3K/AKT/mTOR (PAM) signaling pathway plays a crucial role in cell survival, growth, and cell cycle progression. Dysregulation of this pathway is associated with cancer development and resistance to therapy. This review focuses on the major dysregulations in the PAM signaling pathway in cancer and discusses strategies for overcoming treatment resistance. The role of PAM signaling in immunology and immunotherapies is also discussed.
Article
Biochemistry & Molecular Biology
Xin Gao, Fang Zhao, Yang Wang, Xiaodong Ma, Huayi Chai, Jingjing Han, Fang Fang
Summary: A series of hybrid compounds consisting of mTOR inhibitor and NO donor were designed and synthesized. Half of the compounds showed attractive mTOR inhibitory activity and exhibited higher anti-proliferative activity against various cancer cells compared to the clinical investigated mTOR inhibitor MLN0128. In particular, compound 19f demonstrated the best anti-proliferative activity and reduced the levels of Phos-Akt and Phos-S6 in HL-60 cells in a dose-dependent manner. Therefore, 19f shows potential as a novel mTOR-based multi-target anti-cancer agent.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Review
Oncology
Abdelhakim Bouyahya, Aicha El Allam, Sara Aboulaghras, Saad Bakrim, Naoual El Menyiy, Mohammed Merae Alshahrani, Ahmed Abdullah Al Awadh, Taoufiq Benali, Learn-Han Lee, Nasreddine El Omari, Khang Wen Goh, Long Chiau Ming, Mohammad S. Mubarak
Summary: This review provides an overview of the recent developments in the mTOR signaling pathway and its molecular involvement in various human cancer types, as well as the research progress of different mTOR inhibitors and their rational combinations with immunotherapies.
Article
Pharmacology & Pharmacy
Yu-Fei Chen, Yan-Chun Pang, Han-Chen Wang, Pei-En Wu, Zi-Jie Chen, Da Huang, Dong-Ling Peng, Yong-Ming Yan, Changhui Liu, Li-Chuan Wu, Xiang-Zhen Fan, Yong-Xian Cheng, Yong-Qiang Liu
Summary: The bioactive compound ArC in Centipeda minima extracts has synergistic cytotoxic effects with DNA cross-linking drugs in non-small cell lung cancer cells, by inhibiting the mTOR/E2F1/FANCD2 signaling axis and suppressing DNA damage response.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Xue-Song Xiang, Peng-Cheng Li, Wen-Quan Wang, Liang Liu
Summary: Pancreatic cancer is the seventh leading cause of cancer death worldwide and novel treatment options for PDAC are urgently needed. The dysregulation of HDACs has been identified in association with PDAC and may represent a therapeutic breakthrough. However, the contributions of HDACs to PDAC remain controversial and pharmacokinetic challenges limit the application of HDACis in PDAC.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Chemistry, Medicinal
Bin Zhang, Chengchen Zhu, Albert S. C. Chan, Gui Lu
Summary: This study reports the discovery of irreversible inhibitors for Aurora A kinase, which play critical roles in cell cycle regulation and mitotic spindle assembly. One of the inhibitors, 11c, showed selective inhibition against normal and cancer cells, as well as Aurora A and B kinases. The study suggests that 11c may be a promising drug candidate for the treatment of triple negative breast cancer.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Liang Zhang, Kangjing Qi, Jie Xu, Yan Xing, Xuejian Wang, Ling Tong, Zengguo He, Wenfang Xu, Xiaoyang Li, Yuqi Jiang
Summary: ProTide and cyclic phosphate ester are two successful prodrug technologies to enhance the efficacy of nucleoside drugs. In this study, we designed novel ProTide and cyclic phosphate ester prodrugs of gemcitabine. The cyclic phosphate ester derivative 18c showed significantly higher anti-proliferative activity compared to the positive control, with potent cytotoxicity and prolonged anti-tumor activity. Moreover, we separated and characterized the two P chiral diastereomers of gemcitabine cyclic phosphate ester prodrugs for the first time, highlighting their similar potency and metabolic profile. Compound 18c exhibited promising in vivo anti-tumor activity in prostate and pancreatic cancer models.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Lukasz Swiatek, Elwira Sieniawska, Kouadio Ibrahime Sinan, Gokhan Zengin, Anastazja Boguszewska, Benita Hryc, Kouadio Bene, Malgorzata Polz-Dacewicz, Stefano Dall'Acqua
Summary: This study investigated the chemical profiles and biological properties of Justicia secunda extracts obtained using different solvents. Over 50 compounds, including flavonoids, phenolic acids, and alkaloids, were identified using LC-MS. The methanol and water extracts showed higher phenolic and flavonoid contents and stronger antioxidant abilities. The dichloromethane and ethyl acetate extracts exhibited greater activity against alpha-amylase and alpha-glucosidase. The aqueous extracts demonstrated selective anticancer properties and the methanolic extract decreased the infectious titer and viral load of human herpesvirus type-1. Overall, J. secunda could be used as a multifunctional bioactive raw material for managing diseases related to oxidative stress.
Article
Biochemical Research Methods
Kerstin Lenhof, Nico Gerstner, Tim Kehl, Lea Eckhart, Lara Schneider, Hans-Peter Lenhof
Summary: The goal of personalized medicine in oncology is to optimize treatment strategies based on genetic and molecular profiles of cancer cells. The new MERIDA method is able to predict drug sensitivity effectively, with faster running times and more interpretable models compared to the LOBICO method, potentially deepening our understanding of cancer treatment mechanisms.
Review
Biochemistry & Molecular Biology
Torki A. Zughaibi, Mohd Suhail, Mohammad Tarique, Shams Tabrez
Summary: Cancer is a leading cause of death globally, and current therapies often fail due to side effects, drug resistance, and limited accessibility. Studies have shown that flavonoids, found in herbal/plant sources, may act as complementary treatments for cancer patients with their broad biological properties and anticancer activity by affecting different signaling cascades.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Serge Mignani, Jerome Bignon, Xiangyang Shi, Jean-Pierre Majoral
Summary: Phosphorus dendrimers and dendrons have shown significant advantages as drugs, especially in anti-cancer and anti-tuberculosis applications. The biological activities of these molecules depend on the chemical groups on their surface and their generation levels. Lessons learned from the study indicate the importance of generation levels in determining the effectiveness of these molecules in different therapeutic applications.
Review
Biochemistry & Molecular Biology
Wencheng Fu, Geng Wu
Summary: The balance between anabolism and catabolism is disrupted with aging, with mTOR playing a key role in enhancing anabolism and inhibiting catabolism. Downregulation of the mTOR signaling pathway has been found to extend lifespan and mimic the effects of calorie restriction. In addition to anti-aging effects, mTOR signaling has also been implicated in cancer therapy, with rapamycin and rapalogs showing efficacy in certain tumor growth prevention.