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
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
Oncology
Wojciech Wiese, Julia Barczuk, Olga Racinska, Natalia Siwecka, Wioletta Rozpedek-Kaminska, Artur Slupianek, Radoslaw Sierpinski, Ireneusz Majsterek
Summary: The PI3K/Akt/mTOR pathway is crucial in cancer development and can be a potential therapeutic target for leukemia. Recent research indicates that inhibition of this pathway may lead to improved treatment outcomes for leukemia.
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
Oncology
Le Yu, Jessica Wei, Pengda Liu
Summary: This article reviews the mechanisms leading to the hyperactivation of PI3K/Akt/mTOR signaling in cancer and summarizes the efforts in developing PI3K/Akt/mTOR inhibitors as monotherapy or combination therapy in different cancer settings. Targeting the PI3K/Akt/mTOR signaling pathway through the development of new agents, drug delivery systems, or combination regimens provides insights into possible future directions for targeted therapeutic regimen and effective patient stratification strategy to improve clinical outcomes for cancer patients with deregulated PI3K/Akt/mTOR signaling.
SEMINARS IN CANCER BIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Maria Sofia Basile, Eugenio Cavalli, James McCubrey, Jorge Hernandez-Bello, Jose Francisco Munoz-Valle, Paolo Fagone, Ferdinando Nicoletti
Summary: This review examines the involvement of the PI3K/Akt/mTOR pathway in COVID-19 and discusses the potential use of specific inhibitors of this pathway for treating the disease.
DRUG DISCOVERY TODAY
(2022)
Review
Biochemistry & Molecular Biology
Krisida Cerma, Federico Piacentini, Luca Moscetti, Monica Barbolini, Fabio Canino, Antonio Tornincasa, Federica Caggia, Sara Cerri, Alessia Molinaro, Massimo Dominici, Claudia Omarini
Summary: Breast cancer is the most common and deadliest cancer in women, and new drugs often have limited clinical benefits. Mutations in the PI3K/AKT/mTOR pathway are frequent in breast cancer and contribute to aggressive tumor behavior and treatment resistance. Understanding the role of PI3K-mTORC1/C2 mutations in different breast cancer subtypes is crucial for improving clinical outcomes and treatment efficacy. A broad knowledge of tumor biology will be essential for personalized breast cancer therapy in the era of precision medicine.
Review
Biochemistry & Molecular Biology
Silviu Stanciu, Florentina Ionita-Radu, Constantin Stefani, Daniela Miricescu, Iulia-Ioana Stanescu-Spinu, Maria Greabu, Alexandra Ripszky Totan, Mariana Jinga
Summary: Pancreatic cancer, although relatively rare, is becoming a leading cause of cancer death. Various risk factors, both modifiable and non-modifiable, contribute to its pathogenesis. Chronic inflammation plays a crucial role in the development of pancreatic cancer. The PI3K/AKT/mTOR signaling pathway is important in cell growth, survival, and motility.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Haibo Zhang, Lei Ma, Eungyung Kim, Junkoo Yi, Hai Huang, Hyeonjin Kim, Muhammad Atif Raza, Sijun Park, Soyoung Jang, Kirim Kim, Sung-Hyun Kim, Youngkyun Lee, Eunkyong Kim, Zae Young Ryoo, Myoung Ok Kim
Summary: This study aimed to investigate the potential anticancer activity and underlying mechanisms of rhein, a natural compound extracted from rhubarb, on oral cancer cells. The results showed that rhein significantly inhibited oral cancer cell growth by inducing apoptosis and S-phase cell cycle arrest. It also inhibited migration and invasion of oral cancer cells through the regulation of epithelial-mesenchymal transition-related proteins. Rhein exerted its anticancer activity by inducing oral cancer cell apoptosis and ROS accumulation via the AKT/mTOR signaling pathway in vitro and in vivo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Zihan Quan, Yang Yang, Hongmei Zheng, Yuting Zhan, Jiadi Luo, Yue Ning, Songqing Fan
Summary: The discovery of immune checkpoints has provided new clues for cancer treatments. Immunotherapy targeting PD-1/PD-L1 has been widely used in various tumor treatments, but side effects and drug resistance are challenges. The PI3K/AKT/mTOR pathway may regulate PD-L1 expression through post-transcription and translation. The interaction between PD-1/PD-L1 and PI3K/AKT/mTOR pathway affects both tumor cells and the tumor immune microenvironment. Combination therapy shows great research value for better therapeutic effect and quality of survival. This review summarizes the interaction between PD-1/PD-L1 and the PI3K/AKT/mTOR pathway in NSCLC and its clinical implications, broadening the therapies for NSCLC.
Article
Food Science & Technology
Wen-Ling Wang, Shih-Ming Chen, Yueh-Chun Lee, Wen-Wei Chang
Summary: Stigmasterol inhibits proliferation and migration of endometrial cancer cells, and reduces cancer stem cell activity by inhibiting the IGF1R/AKT/mTOR pathway.
JOURNAL OF FUNCTIONAL FOODS
(2022)
Article
Medicine, Research & Experimental
Maryam Akbarzadeh, Ainaz Mihanfar, Shabnam Akbarzadeh, Bahman Yousefi, Maryam Majidinia
Summary: The PI3K/AKT/mTOR signaling pathway plays a crucial role in cancer and has been found to interact with miRNAs, which is important for understanding cancer biology.
Article
Biochemistry & Molecular Biology
Shixin Chan, Xu Wang, Zhenglin Wang, Youwen Du, Xiaomin Zuo, Jiajie Chen, Rui Sun, Qing Zhang, Li Lin, Yang Yang, Zhen Yu, Hu Zhao, Huabing Zhang, Wei Chen
Summary: This study found that CTSG expression is inhibited in colorectal cancer tissues, and patients with low CTSG expression have poor overall survival. Functional experiments showed that CTSG overexpression suppressed CRC cell progression, while CTSG suppression supported CRC development. Mechanistically, CTSG overexpression suppressed the Akt/mTOR signaling mechanism and elevated apoptotic-associated markers, while CTSG silencing activated the Akt/mTOR signaling mechanism and inhibited apoptotic-associated markers.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Review
Oncology
Huayi Li, Lorenzo Prever, Emilio Hirsch, Federico Gulluni
Summary: The PI3K signaling pathway is crucial in breast cancer and inhibitors targeting this pathway show promising activity, but resistance and adverse reactions limit their efficacy. Combination therapies and identifying suitable patient subpopulations are needed to enhance therapeutic benefit.
Article
Oncology
Haowei Wang, Yujia Chen, Qinzi Yuan, Lixia Chen, Peiling Dai, Xuenong Li
Summary: This study found that HRK is lowly expressed in colorectal cancer tissues. For the first time, it was shown that HRK promotes apoptosis and inhibits proliferation of colorectal cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway. HRK represents a potential target for the treatment of colorectal cancer.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Milad Ashrafizadeh, Ali Zarrabi, Hassan Karimi-Maleh, Afshin Taheriazam, Sepideh Mirzaei, Mehrdad Hashemi, Kiavash Hushmandi, Pooyan Makvandi, Ehsan Nazarzadeh Zare, Esmaeel Sharifi, Arul Goel, Lingzhi Wang, Jun Ren, Yavuz Nuri Ertas, Alan Prem Kumar, Yuzhuo Wang, Navid Rabiee, Gautam Sethi, Zhaowu Ma
Summary: Nanomedicine has great potential in the treatment of bladder cancer, including improving drug efficacy, regulating gene expression, providing photodynamic and photothermal therapy, remodeling tumor microenvironment and infiltration of immune cells, timely diagnosis, and targeted therapy for bladder cancer.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Review
Oncology
Ramya Venkat, Elika Verma, Uzini Devi Daimary, Aviral Kumar, Sosmitha Girisa, Uma Dutta, Kwang Seok Ahn, Ajaikumar B. Kunnumakkara
Summary: This article reviews the molecular targets, biological activities, and beneficial effects of resveratrol (RSV) as an anti-inflammatory compound for the prevention and treatment of inflammation-mediated chronic disorders. RSV has been found to have anti-aging, anti-cancer, anti-inflammatory, antioxidant, and cardio protective properties. However, its rapid elimination through the metabolic system and low bio-availability is a significant issue that requires further study.
CANCER INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Bhagyashree Deka, Pratap Chandra, Priyanka Yadav, Ayushi Rehman, Sweta Kumari, Ajaikumar B. Kunnumakkara, Kusum Kumari Singh
Summary: This study reveals that RNPS1 is highly expressed in cervical carcinoma and promotes cell proliferation, migration, and invasion. Furthermore, RNPS1 regulates alternative splicing of key genes and promotes the formation of tumor-associated splice variants. These findings suggest that RNPS1 plays a significant role in the development of cervical cancer.
Review
Biotechnology & Applied Microbiology
Milad Ashrafizadeh, Kiavash Hushmandi, Sepideh Mirzaei, Saied Bokaie, Ashkan Bigham, Pooyan Makvandi, Navid Rabiee, Vijay Kumar Thakur, Alan Prem Kumar, Esmaeel Sharifi, Rajender S. Varma, Amir Reza Aref, Marcin Wojnilowicz, Ali Zarrabi, Hassan Karimi-Maleh, Nicolas H. Voelcker, Ebrahim Mostafavi, Gorka Orive
Summary: Green chemistry has shown great promise in biomedical applications, particularly in cancer therapy. Chitosan-based nanoparticles (CS-NPs) serve as a promising carrier for anti-cancer drugs, overcoming drug resistance and enabling synergistic therapy. Various types of nanostructures can be modified with chitosan for efficient delivery of chemotherapeutic agents such as doxorubicin (DOX). The functionalization of CS-NPs with ligands and their pH-sensitive and redox-responsive characteristics further enhance their selectivity and drug release. Considering their high encapsulation efficiency and biocompatibility, significant progress is expected in the clinical translation of CS-NPs.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Review
Oncology
Mangala Hegde, Sosmitha Girisa, Nikunj Naliyadhara, Aviral Kumar, Mohammed S. Alqahtani, Mohamed Abbas, Chakrabhavi Dhananjaya Mohan, Sudha Warrier, Kam Man Hui, Kanchugarakoppal S. Rangappa, Gautam Sethi, Ajaikumar B. Kunnumakkara
Summary: This review focuses on the therapeutic effects of natural compounds targeting nuclear receptors (NRs) in cancer treatment, highlighting their advantages and limitations. The study emphasizes the importance of NRs in gene expression regulation and the potential of natural compounds as oncology drugs.
CANCER AND METASTASIS REVIEWS
(2023)
Article
Food Science & Technology
Nikunj Naliyadhara, Aviral Kumar, Shailendra Kumar Gangwar, Thulsidharan Nair Devanarayanan, Mangala Hegde, Mohammed S. Alqahtani, Mohamed Abbas, Gautam Sethi, Ajaikumar Kunnumakara
Summary: The human gastrointestinal tract contains a diverse range of microbial species, which play a role in regulating gut barrier homeostasis, immune system stimulation, and neurological health benefits through the gut-brain axis. Dietary changes can significantly affect the gut microbial population, and positive changes can be made by changing dietary style. Dietary antioxidants, such as those found in food, have been found to have a positive impact on gut microbial populations, which can help alleviate gut microbial dysbiosis and contribute to the development of gut microbe-targeting therapeutics for various diseases. This review discusses the health benefits of major dietary antioxidant groups, and the interaction between gut microbiota and these antioxidants through pre-clinical and human dietary interventions.
JOURNAL OF FUNCTIONAL FOODS
(2023)
Correction
Chemistry, Medicinal
Elina Khatoon, Mangala Hegde, Aviral Kumar, Uzini Devi Daimary, Gautam Sethi, Anupam Bishayee, Ajaikumar B. Kunnumakkara
ARCHIVES OF PHARMACAL RESEARCH
(2023)
Article
Oncology
Mangala Hegde, Nikunj Naliyadhara, Jyothsna Unnikrishnan, Mohammed S. Alqahtani, Mohamed Abbas, Sosmitha Girisa, Gautam Sethi, Ajaikumar B. Kunnumakkara
Summary: Metastasis is the main cause of cancer-related deaths, and despite advancements in treatment methods, it remains difficult to treat. Nanotechnology has shown promising applications in the diagnosis and treatment of metastatic cancer, with nanoparticles demonstrating the ability to target specific cells within metastatic regions. This review summarizes the current state of nanotechnology in the field and discusses its potential in various imaging techniques and combination therapies.
Article
Medicine, Research & Experimental
Na Young Kim, In Jin Ha, Jae-Young Um, Alan Prem Kumar, Gautam Sethi, Kwang Seok Ahn
Summary: This study found that LGA can effectively inhibit the proliferation, invasive ability, and migration of hepatocellular carcinoma cells, and reduce the occurrence of EMT by suppressing MnSOD expression. This has important implications for the development of novel anti-metastatic agents.
Review
Chemistry, Medicinal
Hui Li Ang, Chakrabhavi Dhananjaya Mohan, Muthu K. Shanmugam, Hin Chong Leong, Pooyan Makvandi, Kanchugarakoppal S. Rangappa, Anupam Bishyaee, Alan Prem Kumar, Gautam Sethi
Summary: Epithelial-mesenchymal transition (EMT) is a crucial process in which epithelial cells transform into mesenchymal cells, playing a significant role in tumor progression and resistance to therapy. Various factors, such as signaling pathways, transcriptional regulators, noncoding RNAs, and epigenetic alterations, are involved in the regulation of EMT. However, despite preclinical data, there is a lack of clinical translation in targeting EMT therapeutically. This review discusses the role of these factors in EMT regulation, the contribution of EMT to drug resistance, and potential therapeutic interventions using natural products and nano-formulations as EMT blockers.
MEDICINAL RESEARCH REVIEWS
(2023)
Review
Cell Biology
Aviral Kumar, Sosmitha Girisa, Mohammed S. Alqahtani, Mohamed Abbas, Mangala Hegde, Gautam Sethi, Ajaikumar B. Kunnumakkara
Summary: Cancer is a global health hazard causing 10 million deaths in 2020, and although different treatment approaches have improved overall survival, advanced-stage treatment still has poor outcomes. Autophagy, a catabolic process, plays a role in cancer by maintaining cellular homeostasis and has both tumor-promoting and suppressive effects. Recent research has identified long non-coding RNAs (lncRNAs) as regulators of autophagy and their modulation of various cancer hallmarks. This review discusses the mechanistic role of lncRNAs in modulating autophagy and related proteins in different cancers.
Article
Chemistry, Multidisciplinary
Mangala Hegde, Sosmitha Girisa, Bandari BharathwajChetty, Ravichandran Vishwa, Ajaikumar B. Kunnumakkara
Summary: Curcumin has a wide range of pharmacological properties that can prevent and treat various chronic diseases. However, its weak solubility and bioavailability limit its potential as an oral medication. Different formulation techniques have been investigated to improve its oral bioavailability. We reviewed clinical trials on curcumin formulations and their safety and efficacy, as well as the advantages and limitations compared to other therapies.
Review
Biotechnology & Applied Microbiology
Xin Yuan Lim, Sharah Mae Capinpin, Nagarjun Bolem, Aaron Song Chuan Foo, Wai-Cheong George Yip, Alan Prem Kumar, Daniel Boon Loong Teh
Summary: Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options due to the difficulty of drugs crossing the blood-brain barrier (BBB) and tumor heterogeneity. Nanoparticle (NP) drug carriers have shown promise in targeting cells beyond the BBB. This review focuses on biomimetic NPs in GBM therapy and their potential in overcoming physiological and anatomical challenges.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Review
Oncology
Aranka Brockmueller, Anjana Sajeev, Lenka Koklesova, Samson Mathews Samuel, Peter Kubatka, Dietrich Busselberg, Ajaikumar B. Kunnumakkara, Mehdi Shakibaei
Summary: Despite medical treatment successes, colorectal cancer (CRC) remains a leading cause of cancer deaths worldwide. Chemotherapy can lead to side effects and drug resistance, highlighting the need for natural compounds that can sensitize cancer cells to overcome resistance. Resveratrol, a natural polyphenolic compound, has been shown to enhance the effectiveness of chemotherapy by modulating multiple pathways in CRC cells.
CANCER AND METASTASIS REVIEWS
(2023)
Article
Pharmacology & Pharmacy
Aranka Brockmueller, Sosmitha Girisa, Mahzad Motallebi, Ajaikumar B. Kunnumakkara, Mehdi Shakibaei
Summary: A study found that Calebin A (CA), a compound derived from turmeric, inhibits colorectal cancer (CRC) cell migration by modulating the NF-kappa B pathway through the inhibition of HIF-1 alpha. CA suppressed the proliferation and migration of CRC cells, reduced the expression of metastatic factors, and induced apoptosis through inhibition of HIF-1 alpha. This research has important implications for cancer therapy.
FRONTIERS IN PHARMACOLOGY
(2023)
