Review
Oncology
Zeinab Davoodi-Moghaddam, Farideh Jafari-Raddani, Mahda Delshad, Atieh Pourbagheri-Sigaroodi, Davood Bashash
Summary: The PI3K/AKT/mTOR signaling pathway plays a crucial role in cancer by regulating proliferation, survival, and metabolism. However, the development of inhibitors targeting this pathway in clinical trials has been challenging, with only a few approved by the FDA. In this systematic review, we analyzed over 2250 included studies and more than 100 phase III-IV clinical trials to identify promising therapies and shed light on future research directions for PI3K/AKT/mTOR inhibitors in human malignancies.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Pharmacology & Pharmacy
Zhoupeng Li, Fang Wang, Yongsheng Liu, Dongshen Zhai, Xiaoxiao Zhang, Qikang Ying, Min Jia, Xiaoyan Xue, Jingru Meng, Jing Li, Xingan Wu, Mingkai Li
Summary: A study found that the coumarin derivative N6 shows strong inhibitory effects on HTNV, and early administration can effectively inhibit virus replication and production. Molecular docking results show that N6 interacts with key amino acid residues, and the treatment can inhibit the expression of specific proteins.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yan He, Miao Miao Sun, Guo Geng Zhang, Jing Yang, Kui Sheng Chen, Wen Wen Xu, Bin Li
Summary: The PI3K/Akt signaling pathway plays a crucial role in cancer, and targeting inhibitors against it may aid in drug discovery. Additionally, combining pathway inhibitors with other cancer treatment strategies could be an effective approach to solving therapeutic dilemmas.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Dong Han, Wei Wang, Julie Heejin Jeon, Tao Shen, Xiangsheng Huang, Ping Yi, Bingning Dong, Feng Yang
Summary: Phosphoinositide-dependent kinase-1 (PDK1) is a master kinase that regulates cancer cell proliferation, survival, and metabolism. It phosphorylates/activates AKT and other AGC kinases, including MAPK4, promoting tumor growth. MAPK4 can independently promote AKT activation and tumor growth, and also enhance PDK1 protein synthesis, leading to the activation of PDK1 substrates beyond AKT. Co-targeting AKT and PDK1 effectively represses MAPK4-induced cancer cell growth, providing a potential therapeutic strategy for MAPK4-high cancers.
Review
Cell Biology
Shaobin Yang, Yaqin Du, Xiaoqian Zhao, Chendong Wu, Peng Yu
Summary: The study provides an overview of the neuropathology of Alzheimer's disease (AD) and the role of the PDK1/Akt signaling pathway in its pathophysiology. It discusses the modulation of AD by the PDK1/Akt/TACE signaling axis and its potential for therapeutic targeting.
Review
Pharmacology & Pharmacy
Ayda Baghery Saghchy Khorasani, Atieh Pourbagheri-Sigaroodi, Ali Pirsalehi, Ava Safaroghli-azar, Mohammad Reza Zali, Davood Bashash
Summary: Genetic and epigenetic alterations have long been the focus of cancer pathogenesis research, with dysregulated genes and protein products potentially affecting cancer cell growth through signaling cascades regulating cell survival and metabolism. The activation of the phosphatidylinositol-3-kinase (PI3K) axis in about one-third of human cancers, including gastric cancer, plays a significant role in the development of malignancies. This indicates the potential importance of targeting this axis in therapeutic strategies for such cancers.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Immunology
Preeti Vyas, Rajkumar Tulsawani, Divya Vohora
Summary: Recent findings show that neuroinflammation is closely related to seizures, and the PI3K/Akt/mTOR pathway is speculated to be a potential target for treating neuroinflammation-mediated seizures and neurodegeneration. In a study on mice, PI3K inhibitors buparlisib and dactolisib were found to be effective in prolonging seizure latency and reducing neuronal loss, while rapamycin showed some resistance. The study suggests that targeting the PI3K pathway may offer new approaches for seizure therapies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Karina A. Miller, Seamus Degan, Yanqing Wang, Joseph Cohen, Sheng Yu Ku, David W. Goodrich, Irwin H. Gelman
Summary: PTEN loss is a common mutation in prostate cancer, driving disease progression through AKT activation. Different transgenic prostate cancer models with Akt activation and Rb loss exhibit different metastatic outcomes. PTEN deficiency is correlated with increased dependence on p110 beta and AKT2 for metastatic growth or motility, and downregulation of the metastasis suppressor SMAD4. On the other hand, PTEN expression is associated with greater dependence on p110 alpha and AKT1.
Article
Oncology
Fei Li, Weiwei Xie, Yunze Fang, Kunfeng Xie, Wendong Liu, Lina Hou, Wanlong Tan
Summary: HnRNP-F promotes the proliferation of BC cells through the PI3K/AKT pathway and is regulated by phosphorylation of FOXO1.
Article
Chemistry, Physical
Lin Yang, Xueying An, Wang Gong, Wenshu Wu, Bin Liu, Xiaoyan Shao, Yansi Xian, Rui Peng, Baosheng Guo, Qing Jiang
Summary: This study investigates the potential of alpha-cyperone (alpha-CYP) as a therapeutic agent for osteoporosis and develops a liposome-based nano-drug delivery system that specifically targets bone resorption. The results demonstrate that alpha-CYP inhibits osteoclast differentiation and the progression of osteoporosis by silencing the PI3K/Akt pathway. The liposome targeting delivery system loaded with alpha-CYP shows enhanced efficacy in inhibiting osteoclasts and may provide a novel strategy for treating osteoporosis.
Review
Immunology
Ebru Aydin, Sebastian Faehling, Mariam Saleh, Laura Llao Cid, Martina Seiffert, Philipp M. Roessner
Summary: PI3K pathway plays a crucial role in cell growth and malignant transformation, with its hyperactivation being a hallmark of cancer. Inhibiting PI3K not only affects cancer cells but also impacts the tumor microenvironment and immune cell function. Understanding the effects of PI3K inhibition on the tumor microenvironment in CLL can lead to improved drug development and novel combinatory treatment strategies.
FRONTIERS IN IMMUNOLOGY
(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.
Review
Pharmacology & Pharmacy
Nazanin Momeni Roudsari, Naser-Aldin Lashgari, Saeideh Momtaz, Shaghayegh Abaft, Fatemeh Jamali, Pardis Safaiepour, Kiyana Narimisa, Gloria Jackson, Anusha Bishayee, Nima Rezaei, Amir Hossein Abdolghaffari, Anupam Bishayee
Summary: The importance of the PI3K/Akt/mTOR pathway in prostate cancer treatment and the clinical applications of natural agents and small molecule inhibitors targeting this pathway are discussed in the study. Research suggests that natural mTOR inhibitors can interfere with the PI3K/Akt/mTOR pathway through multiple mechanisms, with inhibition of Akt and suppression of mTOR 1 activity being the main therapeutic approaches. Combination therapy has been shown to improve the efficacy of these inhibitors in suppressing prostate cancer progression or overcoming resistance by cancer cells.
Article
Plant Sciences
Meizhu Zheng, Minghui Chen, Wenli Wang, Mi Zhou, Chunming Liu, Yajun Fan, Dongfang Shi
Summary: Rhy has been shown to have a neuroprotective effect by activating the PI3K/Akt signaling pathway, improving cell viability, inhibiting apoptosis, and reducing levels of LDH, [Ca2+]i, and ROS in models of Parkinson's disease.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Natasha M. Setiabakti, Pia Larsson, Justin R. Hamilton
Summary: Understanding the role of phosphoinositide 3-kinases (PI3Ks) in platelet function and thrombus formation is crucial for the development of therapeutic drugs for thrombotic cardiovascular diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
V. Dimitrova, A. Arcaro
CURRENT MOLECULAR MEDICINE
(2015)
Editorial Material
Cell Biology
Alexandre Arcaro
Meeting Abstract
Oncology
Krithika Sundaram, Ian Jennings, Alexandre Arcaro, Philip Thompson
Article
Oncology
Anna Wojtalla, Barbara Fischer, Nataliya Kotelevets, Francesco A. Mauri, Jens Sobek, Hubert Rehrauer, Carlos Wotzkow, Mario P. Tschan, Michael J. Seckl, Uwe Zangemeister-Wittke, Alexandre Arcaro
CLINICAL CANCER RESEARCH
(2013)
Article
Pharmacology & Pharmacy
Alexandre Arcaro, Anna Borgstroem, Karolina Blajecka
CURRENT SIGNAL TRANSDUCTION THERAPY
(2013)
Article
Biochemistry & Molecular Biology
F. Salm, P. Cwiek, A. Ghosal, A. Lucia Buccarello, F. Largey, C. Wotzkow, K. Hoeland, B. Styp-Rekowska, V. Djonov, I. Zlobec, N. Bodmer, N. Gross, F. Westermann, S. C. Schaefer, A. Arcaro
Article
Multidisciplinary Sciences
Karolina Blajecka, Marin Marinov, Laura Leitner, Kristin Uth, Guido Posern, Alexandre Arcaro
Article
Multidisciplinary Sciences
Yang Liu, Andres Kaech, Urs Ziegler, Albert C. M. Ong, Darren P. Wallace, Alexandre Arcaro, Andreas L. Serra
Article
Multidisciplinary Sciences
Katrin Hoeland, Danielle Boller, Christian Hagel, Silvia Dolski, Andras Treszl, Olivier E. Pardo, Paulina Cwiek, Fabiana Salm, Zaira Leni, Peter R. Shepherd, Beata Styp-Rekowska, Valentin Djonov, Andre O. von Bueren, Karl Frei, Alexandre Arcaro
Article
Multidisciplinary Sciences
Fabiana Salm, Valeriya Dimitrova, Andre O. von Bueren, Paulina Cwiek, Hubert Rehrauer, Valentin Djonov, Pascale Anderle, Alexandre Arcaro
Review
Pharmacology & Pharmacy
Alexandre Arcaro
FRONTIERS IN PHARMACOLOGY
(2013)
Article
Neurosciences
Giulio Fiaschetti, Christina Schroeder, Deborah Castelletti, Alexandre Arcaro, Frank Westermann, Martin Baumgartner, Tarek Shalaby, Michael A. Grotzer
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2014)
Article
Oncology
Paulina Cwiek, Zaira Leni, Fabiana Salm, Valeriya Dimitrova, Beata Styp-Rekowska, Gianpaolo Chiriano, Michael Carroll, Katrin Hoeland, Valentin Djonov, Leonardo Scapozza, Patrick Guiry, Alexandre Arcaro
Article
Oncology
Danielle Boller, Kathrin T. Doepfner, Angela De Laurentiis, Ana S. Guerreiro, Marin Marinov, Tarek Shalaby, Paul Depledge, Anthony Robson, Nahid Saghir, Masahiko Hayakawa, Hiroyuki Kaizawa, Tomonobu Koizumi, Takahide Ohishi, Sarah Fattet, Olivier Delattre, Anelia Schweri-Olac, Katrin Hoeland, Michael A. Grotzer, Karl Frei, Olivier Spertini, Michael D. Waterfield, Alexandre Arcaro
ANTICANCER RESEARCH
(2012)
