Review
Oncology
Alexandre el Hage, Olivier Dormond
Summary: Studies have shown that mTOR inhibitors can promote or inhibit immune responses in certain contexts, helping to enhance the anticancer effects of immunotherapy. Various resistance mechanisms to mTOR inhibitors have been identified, highlighting the potential benefits of combination therapies.
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.
Review
Chemistry, Medicinal
Udit Chaube, Rajdeep Dey, Suman Shaw, Bhumika D. Patel, Hardik G. Bhatt
Summary: Efforts have been made to find an efficient scaffold and its substitution for mTOR inhibition in the treatment of lung cancer. A detailed literature search was conducted to find previously reported mTOR inhibitors. This review focuses on lung cancer, providing descriptions of mTOR inhibitors currently in clinical trials for lung cancer treatment. Tetrahydroquinoline (THQ) has been found to be the most efficient scaffold for exploring lung cancer treatment, and a potential substitution for the THQ scaffold may also be beneficial.
FUTURE MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Jiao Zhou, Honghan Chen, Jintao Du, Haoran Tai, Xiaojuan Han, Ning Huang, Xiaobo Wang, Hui Gong, Mingyao Yang, Hengyi Xiao
Summary: Glutamine, an important amino acid involved in energy production and redox homeostasis, plays a crucial role in the aging process. Chronic glutamine deprivation leads to cellular senescence and aging, while glutamine supplementation protects against oxidative stress-induced senescence and progeria. The activation of the Akt-mTOR pathway and impairment of autolysosome function are observed during long-term glutamine deprivation, and inhibition of this pathway rescues the autophagy impairment and cellular senescence caused by glutamine deprivation. These findings provide new insights into the connection between glutamine availability and the aging process.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Cell Biology
Siamak Tabibzadeh
Summary: Autophagy is a crucial process for maintaining cellular metabolic demands and preventing aging, disease, and cancer. Genetic defects in autophagy genes and age-induced decline of autophagy can lead to various abnormalities and loss of cellular control.
Article
Medicine, Research & Experimental
Zofia Chrienova, David Rysanek, Josef Novak, Pavla Vasicova, Patrik Oleksak, Rudolf Andrys, Adam Skarka, Jelena Dumanovic, Zoran Milovanovic, Vesna Jacevic, Marketa Chvojkova, Kristina Holubova, Karel Vales, Veronika Skoupilova, Marian Valko, Klaudia Jomova, Suliman Y. Alomar, Fernanda D. Botelho, Tanos C. C. Franca, Kamil Kuca, Zdenek Hodny, Eugenie Nepovimova
Summary: Frentizole and rapamycin are two drugs with anti-aging and immunosuppressive effects. Through docking, simulation, and calculation, nine Frentizole-like compounds were chosen. Among them, three compounds showed the best results in in vivo testing and were recommended for further safety studies.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Oncology
Dafne Jacome Sanz, Juuli Raivola, Hanna Karvonen, Mariliina Arjama, Harlan Barker, Astrid Murumagi, Daniela Ungureanu
Summary: Ovarian cancer has a poor prognosis due to late diagnosis and lack of reliable biomarkers. Lipid metabolism plays a crucial role in ovarian cancer progression. Targeting enzymes involved in lipid metabolism regulation can impair cancer cell growth. Different mTOR inhibitors show varying levels of cytotoxic activity in ovarian cancer cell lines and patient-derived cancer cell cultures, suggesting the potential for targeted therapies based on subtype-specific drug vulnerabilities.
Review
Chemistry, Medicinal
Han-Yue Qiu, Peng-Fei Wang, Min Zhang
Summary: The review highlights the progress of mTOR inhibitor development with anticancer potential from 2011 to 2020, emphasizing the challenges posed by the highly complex regulatory mechanism network of mTOR. Expert opinion suggests that in-depth biological research and fundamental medchemistry research are essential for improving mTOR inhibitors, while new technologies for pre-diagnosing applicable populations are crucial for providing precise personal cancer treatment.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2021)
Review
Cell Biology
Seraina Faes, Nicolas Demartines, Olivier Dormond
Summary: The importance of the mechanistic target of rapamycin (mTOR) in renal cell carcinoma (RCC) biology is highlighted by its frequent activation in RCC, promoting cancer cell proliferation and survival. Despite its protumorigenic effects, mTOR inhibitors have not provided long-lasting anticancer benefits in RCC patients, calling for a reevaluation of their role in treatment. This review presents the rationale and limitations of targeting mTOR in RCC, as well as discussing the future roles of mTOR inhibitors in RCC treatment, especially in the context of immunotherapies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Mikhail Blagosklonny
Summary: Cellular senescence is characterized by the proliferation-like activity of growth-promoting pathways in non-proliferating cells, leading to geroconversion and hyperfunctional cells. While senescent cells contribute to organismal aging, they are not strictly necessary, and both can be indirectly linked through the same underlying cause.
Review
Chemistry, Medicinal
Patrik Oleksak, Eugenie Nepovimova, Zofia Chrienova, Kamil Musilek, Jiri Patocka, Kamil Kuca
Summary: Mechanistic target of rapamycin (mTOR) is a protein kinase that regulates cell functions. Dysregulation of mTOR activity is associated with various pathological conditions. Inhibition of overactivated mTOR is a rational approach for treating human diseases. Rapamycin is a natural inhibitor of mTOR with antitumor and immunosuppressive activity. Different generations of mTOR inhibitors have been developed, including rapalogs, mTOR kinase inhibitors, and dual PI3K/mTOR inhibitors. Novel inhibitors are still being developed to better understand the role of mTOR in signaling pathways and human diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Adriana De Sousa Lages, Valentim Lopes, Joao Horta, Joao Espregueira-Mendes, Renato Andrade, Alexandre Rebelo-Marques
Summary: Improved healthcare access and social conditions globally have led to a significant increase in life expectancy. However, there is a growing prevalence of age-related diseases, impacting both the individual's quality of life and the sustainability of countries and regions. This narrative review examines potential therapeutic targets that can mimic or enhance the anti-aging effects of physical exercise, although more research is needed to determine their effectiveness.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Liam D. Cassidy, Masashi Narita
Summary: Autophagy is a crucial process for maintaining cellular homeostasis and preventing aging. It also plays a role in tumor development. Autophagy is involved in maintaining stem cell populations and inhibiting cellular senescence, but the decline in autophagy with age may promote tumor growth.
MOLECULAR ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Angel Cayo, Raul Segovia, Whitney Venturini, Rodrigo Moore-Carrasco, Claudio Valenzuela, Nelson Brown
Summary: Cellular senescence is a unique form of proliferative arrest triggered by various stimuli, characterized by changes in cell morphology and function. The activation of mTOR and autophagy play crucial roles in regulating different aspects of cellular senescence. Understanding and targeting the interconnected pathways of mTOR and autophagy could be key in developing anti-cancer therapies involving pro-senescence drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Jing Yang, Mengmeng Liu, Dongchun Hong, Musheng Zeng, Xing Zhang
Summary: Cellular senescence in cancer presents a dual role, acting as both a preventative measure and a promoter of tumor development. Senescent cells contribute to oncogenesis through their secretory phenotype, both inhibiting tumor growth and creating an environment conducive to tumor progression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)