Review
Cell Biology
Kunrui Zhu, Yanqi Wu, Ping He, Yu Fan, Xiaorong Zhong, Hong Zheng, Ting Luo
Summary: Phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and mechanistic target of rapamycin (mTOR) (PAM) pathways play important roles in breast tumorigenesis and offer potential targets for cancer therapy.
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
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)
Article
Oncology
Weikai Xiao, Guochun Zhang, Bo Chen, Xiaoqing Chen, Lingzhu Wen, Jianguo Lai, Xuerui Li, Min Li, Hao Liu, Jing Liu, Han Han-Zhang, Analyn Lizaso, Ning Liao
Summary: Our study identified heterogeneity in the PI3K-AKT-mTOR pathway among breast cancer molecular subtypes in our cohort. The number and specific sites of PIK3CA mutations have distinct prognostic impacts.
Article
Oncology
Qianxu Jin, Jiahui Zhao, Zijun Zhao, Shiyang Zhang, Zhimin Sun, Yunpeng Shi, Hongshan Yan, Yizheng Wang, Liping Liu, Zongmao Zhao
Summary: CAMK1D is expressed at lower levels in glioma tissues and is positively correlated with the WHO classification of gliomas. Knockdown of CAMK1D promotes the proliferation, migration, and invasion of glioma cells, while overexpression has the opposite effect. Mechanistically, CAMK1D regulates glioma cell function through the PI3K/AKT/mTOR pathway. These findings suggest that CAMK1D may serve as a prognostic predictor and a potential therapeutic target for glioma.
FRONTIERS IN ONCOLOGY
(2022)
Review
Pharmacology & Pharmacy
Jieun Bang, Mihyeon Jun, Soyun Lee, Hyuk Moon, Simon Weonsang Ro
Summary: Hepatocellular carcinoma (HCC) is a significant global health concern, with its incidence steadily increasing. Recent progress has been made in understanding the molecular signaling pathways, particularly the EGFR/PI3K/AKT/mTOR pathway, which plays a central role in HCC. Preclinical studies have shown the effectiveness of targeting this signaling pathway for HCC therapy, offering potential therapeutic options for patients.
Article
Oncology
Lei Wang, Zhiyu Fang, Peixiang Gao, Junfang Zheng
Summary: This study reveals a novel tumor-suppressing role of GLUD1 in ccRCC, providing new insights into inhibiting PI3K/Akt/mTOR activation and immune microenvironment.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Stefano Ratti, Raffaella Mauro, Cristina Rocchi, Sara Mongiorgi, Giulia Ramazzotti, Mauro Gargiulo, Lucia Manzoli, Lucio Cocco, Roberta Fiume
Summary: This review examines the importance of critical enzymes such as PI3K, AKT, and mTOR in the maturation and failure of arteriovenous fistula (AVF) for haemodialysis treatment. These enzymes play a role in various cellular activities and are associated with multiple diseases. They are also druggable targets, which can be targeted to control specific aspects of AVF and provide more personalized therapy.
Review
Biochemistry & Molecular Biology
Elisabetta Tortorella, Sabrina Giantulli, Alessandro Sciarra, Ida Silvestri
Summary: Prostate cancer (PCa) is a common cancer in men, and the androgen receptor (AR) plays a crucial role in its development and progression. Although AR signaling inhibitors (ARSIs) have shown effectiveness in castration-sensitive PCa (CSPC) and improved survival, men with castration-resistant PCa (CRPC) still have a poor prognosis. Resistance to ARSIs in metastatic CRPC is commonly observed due to AR mutations and hyperactivation of the PI3K/AKT/mTOR pathway. The interaction between AR and the PI3K/AKT/mTOR signaling pathway in PCa has been well-documented.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Biochemistry & Molecular Biology
Eun Jin Sun, Miriam Wankell, Pranavan Palamuthusingam, Craig McFarlane, Lionel Hebbard
Summary: This review article discusses the pivotal role of the PI3K/Akt/mTOR pathway in HCC, focusing on its impact on cellular processes and providing an update on the ongoing clinical development of therapies targeting this pathway for HCC treatments.
Review
Oncology
Qian Luo, Ruijuan Du, Wenting Liu, Guojing Huang, Zigang Dong, Xiang Li
Summary: Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer worldwide, mainly occurring in specific regions of Asia. The PI3K/Akt/mTOR signaling pathway plays a crucial role in regulating cell growth, differentiation, migration, metabolism, and proliferation, and is closely associated with survival and prognosis in ESCC patients. Many molecules can regulate this pathway and lead to its aberrant activation. Several effective inhibitors of the PI3K/Akt/mTOR pathway have been developed.
FRONTIERS IN ONCOLOGY
(2022)
Review
Pathology
Mohsen Karami Fath, Menooa Ebrahimi, Ehsan Nourbakhsh, Ahmad Zia Hazara, Ali Mirzaei, Saba Shafieyari, Azadeh Salehi, Mahsa Hoseinzadeh, Zahra Payandeh, Ghasem Barati
Summary: Cancer stem cells (CSCs) play a crucial role in tumor formation and resistance to therapy. Understanding the PI3K/Akt/mTOR signaling pathway in CSCs can provide insights into targeted therapy for drug-resistant tumors. While this pathway is well-known in tumor bulk, its functions in CSCs have not been fully explored.
PATHOLOGY RESEARCH AND PRACTICE
(2022)
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.
Review
Oncology
Yan Peng, Yuanyuan Wang, Cheng Zhou, Wuxuan Mei, Changchun Zeng
Summary: Cancer is a global public health issue that hinders the improvement of life expectancy worldwide. Current therapeutic options are insufficient, necessitating targeted treatments. Understanding the association between the PI3K/AKT/mTOR pathway and tumorigenesis, as well as the development of therapies targeting this pathway, is crucial for clinical decision-making.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
James Andrew McCubrey, Stephen L. Abrams, Linda S. Steelman, Lucio Cocco, Stefano Ratti, Alberto M. Martelli, Paolo Lombardi, Agnieszka Gizak, Przemyslaw Duda
Summary: The study indicates that TP53 reactivator APR-246 can increase the therapeutic potential of many modified berberine compounds, which is of significance for pancreatic ductal adenocarcinoma.
Article
Oncology
Silvia Lampis, Salvatore Raieli, Luca Montemurro, Damiano Bartolucci, Camilla Amadesi, Sonia Bortolotti, Silvia Angelucci, Anna Lisa Scardovi, Giammario Nieddu, Lucia Cerisoli, Francesca Paganelli, Sabrina Valente, Matthias Fischer, Alberto Maria Martelli, Gianandrea Pasquinelli, Andrea Pession, Patrizia Hrelia, Roberto Tonelli
Summary: This study found that the combination of MYCN-specific antigene oligonucleotide BGA002 and retinoic acid (RA) can restore sensitivity to RA in MYCN-amplified neuroblastoma (MNA-NB) patients and improve their survival rate. Furthermore, by targeting MYCN, a cancer-specific inhibition of the mTOR pathway occurs only in MNA-NB, avoiding the side effects of targeting mTOR in normal cells.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Rossella Loria, Valentina Laquintana, Stefano Scalera, Rocco Fraioli, Valentina Caprara, Italia Falcone, Chiara Bazzichetto, Marta Di Martile, Laura Rosano, Donatella Del Bufalo, Gianluca Bossi, Isabella Sperduti, Irene Terrenato, Paolo Visca, Silvia Soddu, Michele Milella, Gennaro Ciliberto, Rita Falcioni, Virginia Ferraresi, Giulia Bon
Summary: This study reveals that high expression of SEMA6A is associated with poor prognosis in BRAF-mutant melanoma and plays a critical role in promoting tumor aggressiveness and resistance to targeted therapies. SEMA6A may serve as a potential predictor for the efficacy of dual BRAF/MEK inhibition.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Cell Biology
Francesca Chiarini, Francesca Paganelli, Tommaso Balestra, Cristina Capanni, Antonietta Fazio, Maria Cristina Manara, Lorena Landuzzi, Stefania Petrini, Camilla Evangelisti, Pier-Luigi Lollini, Alberto M. Martelli, Giovanna Lattanzi, Katia Scotlandi
Summary: Lamin A plays a significant role in Ewing Sarcoma by affecting cell migration and invasiveness. Low expression of Lamin A is associated with increased aggressiveness and metastatic load in patients. This effect is linked to altered nuclear envelope proteins and increased nuclear retention of YAP/TAZ. Overexpression of Lamin A or pharmacological modulation of its maturation can prevent cell invasiveness and improve therapeutic strategies for Ewing Sarcoma.
CELL DEATH & DISEASE
(2022)
Review
Cell Biology
Alberto M. Martelli, Francesca Paganelli, Camilla Evangelisti, Francesca Chiarini, James A. McCubrey
Summary: GSK-3 is a multifunctional protein kinase involved in various physiological processes and plays a crucial role in cancer cell pathobiology. While often inactivated in cancer cells, GSK-3 isoforms can also act as tumor promoters in certain contexts.
Article
Cell Biology
Stephen L. Abrams, Przemyslaw Duda, Shaw M. Akula, Linda S. Steelman, Matilde L. Follo, Lucio Cocco, Stefano Ratti, Alberto M. Martelli, Giuseppe Montalto, Maria Rita Emma, Melchiorre Cervello, Dariusz Rakus, Agnieszka Gizak, James A. McCubrey
Summary: TP53 mutation is common in pancreatic cancer and promotes tumor growth and metastasis. APR-246, a molecule that restores wildtype TP53 function, can increase the sensitivity of PDAC cells to chemotherapy. Introduction of WT-TP53 enhances sensitivity to TP53 reactivators, chemotherapeutic drugs, and signal transduction inhibitors in PDAC cells.
Article
Oncology
Fabiana Conciatori, Erica Salvati, Ludovica Ciuffreda, Senji Shirasawa, Italia Falcone, Francesco Cognetti, Gianluigi Ferretti, Massimo Zeuli, Donatella Del Bufalo, Chiara Bazzichetto, Michele Milella
Summary: Soluble factors produced by stromal fibroblasts can influence the sensitivity of tumor cells to molecularly targeted drugs. This influence depends on the genetic mutations and PTEN protein status of the tumor cells.
FRONTIERS IN ONCOLOGY
(2022)
Review
Cell Biology
James A. McCubrey, Li Yang, Stephen L. Abrams, Linda S. Steelman, Matilde Y. Follo, Lucio Cocco, Stefano Ratti, Alberto M. Martelli, Giuseppa Augello, Melchiorre Cervello
Summary: This review discusses the roles of TP53 and miRs in the PDAC tumor microenvironment and how mutated TP53 and loss of miR expression contribute to tumor progression.
Review
Biochemistry & Molecular Biology
Chiara Bazzichetto, Michele Milella, Ilaria Zampiva, Francesca Simionato, Carla Azzurra Amoreo, Simonetta Buglioni, Chiara Pacelli, Loredana Le Pera, Teresa Colombo, Emilio Bria, Massimo Zeuli, Donatella Del Bufalo, Isabella Sperduti, Fabiana Conciatori
Summary: Interleukin-8 (IL-8) plays an important role in colorectal cancer and its high levels are significantly correlated with shorter overall survival and progression-free survival. Circulating IL-8 represents an important prognostic factor in colorectal cancer.
Review
Biochemistry & Molecular Biology
Alberto M. M. Martelli, Francesca Paganelli, Serena Truocchio, Carla Palumbo, Francesca Chiarini, James A. A. McCubrey
Summary: The Hedgehog (HH) signaling network is an important regulator of embryonic development. However, abnormal activation of HH signaling has been found in various malignant disorders, promoting proliferation, survival, and therapeutic resistance of neoplastic cells. In this review, the biological roles and pathophysiology of the HH pathway in normal T-cell lymphopoiesis and T-ALL are summarized, along with potential therapeutic strategies to target the HH pathway in T-ALL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Sonia Bortolotti, Silvia Angelucci, Luca Montemurro, Damiano Bartolucci, Salvatore Raieli, Silvia Lampis, Camilla Amadesi, Annalisa Scardovi, Giammario Nieddu, Lucia Cerisoli, Francesca Paganelli, Francesca Chiarini, Gabriella Teti, Mirella Falconi, Andrea Pession, Patrizia Hrelia, Roberto Tonelli
Summary: Small-cell lung cancer (SCLC) is an aggressive form of lung cancer associated with smoking and low survival rate. Alterations in MYC family genes, particularly MYCN, define an aggressive and immunotherapy resistant subgroup of SCLC. A proposed innovative approach to target MYCN in SCLC is through MYCN-specific expression inhibition using an antigene oligonucleotide (BGA002). BGA002 showed significant MYCN silencing, reversion of specific pathways, induction of cell death, and improved survival in SCLC mouse models.
Article
Cell Biology
Elisabetta Valentini, Marta Di Martile, Matteo Brignone, Marica Di Caprio, Isabella Manni, Michela Chiappa, Ilaria Sergio, Martina Chiacchiarini, Chiara Bazzichetto, Fabiana Conciatori, Simona D'Aguanno, Carmen D'Angelo, Rino Ragno, Michelangelo Russillo, Gianni Colotti, Francesco Marchesi, Maria Laura Bellone, Fabrizio Dal Piaz, Maria Pia Felli, Giovanna Damia, Donatella Del Bufalo
Summary: BH3 mimetics, which target the anti-apoptotic proteins of the Bcl-2 family, have shown promising therapeutic potential in cancer treatment. IS21, a novel pan BH3 mimetic, has been found to have preclinical antitumor activity in various types of tumors. IS21 demonstrated activity in T-cell acute lymphoblastic leukemia, melanoma, lung, pancreatic, and ovarian cancer cell lines.
CELL DEATH & DISEASE
(2023)