PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways inhibitors as anticancer agents: Structural and pharmacological perspectives

European Journal of Medicinal Chemistry
Vivek AsatiSanjay Kumar Bharti

Abstract

The protein kinases regulate cellular functions such as transcription, translation, proliferation, growth and survival by the process of phosphorylation. Over activation of signaling pathways play a major role in oncogenesis. The PI3K signaling pathway is dysregulated almost in all cancers due to the amplification, genetic mutation of PI3K gene and the components of the PI3K pathway themselves. Stimulation of the PI3K/Akt/mTOR and Ras/Raf/MEK/ERK pathways enhances growth, survival, and metabolism of cancer cells. Recently, the PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways have been identified as promising therapeutic targets for cancer therapy. The kinase inhibitors with enhanced specificity and improved pharmacokinetics have been considered for design and development of anticancer agents. This review focuses primarily on the Ras/Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways as therapeutic targets of anticancer drugs, their specific and dual inhibitors, structure activity relationships (SARs) and inhibitors under clinical trials.

References

Jul 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·U R RappJ R Stephenson
Jul 1, 1994·Trends in Biochemical Sciences·J AvruchJ M Kyriakis
Nov 15, 1996·Cell·H G WangJ C Reed
Dec 1, 1996·Environmental Health Perspectives·R D Irons, W S Stillman
Jul 1, 1997·Trends in Biochemical Sciences·B VanhaesebroeckM D Waterfield
Feb 12, 1998·The Journal of Biological Chemistry·M AndjelkovićB A Hemmings
Apr 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·M KobayashiY Fukui
Sep 2, 1999·International Journal of Cancer. Journal International Du Cancer·B GayJ Schoepfer
Dec 2, 1999·Experimental Cell Research·C Hagemann, U R Rapp
Dec 2, 1999·Experimental Cell Research·B Vanhaesebroeck, M D Waterfield
Mar 4, 2000·The Biochemical Journal·B Vanhaesebroeck, D R Alessi
Jun 10, 2000·Molecular and Cellular Biology·A YuryevL P Wennogle
May 5, 2001·The Journal of Biological Chemistry·B D CuevasG B Mills
Jul 3, 2002·Nature Reviews. Cancer·Igor Vivanco, Charles L Sawyers
Jul 18, 2002·Nature Reviews. Drug Discovery·Jason Y Zhang
Jul 18, 2002·Nature Reviews. Drug Discovery·Margaret A Somerville
Aug 1, 2002·The Journal of Biological Chemistry·Nelly Marmy ConusRichard B Pearson
Aug 13, 2002·Nature Cell Biology·Ken InokiKun-Liang Guan
Aug 13, 2002·Nature Cell Biology·Christopher J PotterTian Xu
Nov 7, 2002·Cell·Derek P BrazilBrian A Hemmings
Dec 10, 2002·Experimental Gerontology·Antonello LorenziniVincent J Cristofalo
Jun 26, 2003·Nucleic Acids Research·John C ObenauerMichael B Yaffe
Oct 16, 2003·Biochemical and Biophysical Research Communications·Ning GaoXianglin Shi
Jan 20, 2004·Molecular and Cellular Biology·Lazaros C FoukasPeter R Shepherd
Mar 17, 2004·Cancer Treatment Reviews·Juan Angel Fresno VaraManuel González-Barón
Jul 16, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Isabelle Sansal, William R Sellers
Oct 19, 2004·Cancer Cell·Mathew J Garnett, Richard Marais
Nov 3, 2004·Nature Reviews. Molecular Cell Biology·Claudia WellbrockRichard Marais
Jan 25, 2005·Onkologie·Dirk Strumberg, Siegfried Seeber
Mar 4, 2005·Molecular and Cellular Biology·Michael P ScheidJames R Woodgett
Mar 31, 2005·Blood·John C Reed, Maurizio Pellecchia
Apr 14, 2005·Molecular Cancer Therapeutics·Srikala S SridharLillian L Siu
Jun 16, 2005·Current Opinion in Pharmacology·Neil Thompson, John Lyons
Oct 12, 2005·Bioorganic & Medicinal Chemistry Letters·Ashis K SahaDave W End
Feb 14, 2006·Cell·Stephan WullschlegerMichael N Hall

❮ Previous
Next ❯

Citations

Apr 17, 2016·International Journal of Cardiology·Zuoguang WangYongxiang Wei
Jun 18, 2016·Frontiers in Oncology·Markus Hartl
Oct 9, 2016·Molecular and Cellular Endocrinology·Tanwir HabibTomoshige Kino
Dec 16, 2016·The Journal of Organic Chemistry·Alexandra I EliseevaNataliya P Belskaya
Jun 9, 2017·British Journal of Cancer·Jie WangJianxin Jiang
Jan 24, 2017·The Cancer Journal·Wade T IamsSunandana Chandra
Jan 23, 2017·European Journal of Medicinal Chemistry·Jiankang ZhangYongzhou Hu
Jun 9, 2017·Expert Opinion on Therapeutic Patents·Debarshi Kar MahapatraSanjay Kumar Bharti
Feb 1, 2018·Dose-response : a Publication of International Hormesis Society·Richard SmithCarmel Mothersill
Apr 4, 2017·Organic & Biomolecular Chemistry·Lu WangWeifang Tang
Apr 19, 2018·Basic & Clinical Pharmacology & Toxicology·Jaakko KangasLauri Eklund
Sep 11, 2018·The Journal of Pharmacy and Pharmacology·Asuman Demiroglu-ZergerogluSultan Nacak Baytas
Jan 25, 2019·Bioscience Reports·Guihua WangXudong Wang
Apr 4, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Jingzhe ZhangWenjun Wang
Jul 10, 2019·Expert Opinion on Therapeutic Patents·Peng-Fei WangHai-Liang Zhu
Aug 2, 2019·Bioscience Reports·Madhumitha Kedhari SundaramArif Hussain
Sep 5, 2019·BMC Complementary and Alternative Medicine·Mohd Rohaizad Md RoduanNorhafizah Mohtarrudin
Nov 3, 2017·Nature Communications·Samuel W BradyAndrea H Bild
Feb 15, 2020·Journal of Biochemical and Molecular Toxicology·Zhuo ChenGengren Tian
Feb 20, 2020·International Journal of Molecular Sciences·Gustavo FerrínManuel De la Mata
Apr 2, 2020·International Journal of Molecular Sciences·Heejin LeeSang-Hyun Min
Oct 28, 2019·Mini Reviews in Medicinal Chemistry·Yutao XieYajun Cao
Jun 6, 2020·International Journal of Environmental Research and Public Health·Yueh-Han HsuAnd Chia-Ming Chang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Breast Cancer: Therapeutic Approaches

Several different therapeutic approaches are used to treat breast cancer. These include chemotherapy, hormonal therapy, targeted therapy, and Immunotherapy. Discover the latest research on breast cancer therapeutic approaches here.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Autophagy Networks

Autophagy is a lysosomal pathway that involves degradation of proteins and functions in normal growth and pathological conditions, through a series of complex networks. The catabolic process involves delivery of proteins and organelles to the lysosome. Here is the latest research on autophagy networks.

Cancer Epigenetics & Methyl-CpG (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. Here is the latest research on cancer epigenetics and methyl-CpG binding proteins including ZBTB38.

Breast Invasive Carcinoma

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Breast Tumorigenesis

Breast tumorigenesis involves the production or formation of tumor(s) in breast tissue. Discover the latest research on breast tumorigenesis here.

Autophagy & Metabolism

Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however--cancer cells exploit it to survive in nutrient-poor tumors.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Cancer Epigenetics

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Parkinson's Disease & Autophagy (MDS)

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Breast Invasive Carcinoma (Keystone)

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Adrenocortical Carcinoma

Hepatocellular carcinoma is the most common type of primary liver cancer and frequently occurs in individuals with chronic liver diseases like cirrhosis. Here is the latest research.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.

Breast Cancer: Chemo-Resistance

Some cancers are difficult to treat and aggressive including the "triple-negative" breast cancer. This type of cancer is chemoresistant even before chemotherapy begins. Here are the latest discoveries chemo-resistance in breast cancer.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Cancer Epigenetics and Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.

Cancer Metabolism: Therapeutic Targets

Targeting the mechanisms by which cancer cells acquire energy for metabolic needs is a therapeutic target. Discover the latest research on cancer metabolism and therapeutic targets.

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.

Related Papers

Anti-cancer Agents in Medicinal Chemistry
Asif Khurshid QaziAjit Kumar Saxena
Expert Opinion on Investigational Drugs
Dae-Dong Kim, Cathy Eng
Anticancer Research
Jean-Emmanuel Kurtz, Isabelle Ray-Coquard
© 2021 Meta ULC. All rights reserved