Abstract
Primary liver cancer is one of the most commonly occurring cancers worldwide. Hepatocellular carcinoma (HCC) represents the majority of primary liver cancer and is the 3rd most common cause of cancer-related deaths globally. Survival rates of patients with HCC are dependent upon early detection as concomitant liver dysfunction and advanced disease limits traditional therapeutic options such as resection or ablation. Unfortunately, at the time of diagnosis, most patients are not eligible for curative surgery and have a five-year relative survival rate less than 20%, leading to systemic therapy as the only option. Currently, sorafenib is the only approved systemic therapy; however, it has a limited survival advantage and low efficacy prompting alternative strategies. The inception of sorafenib for HCC systemic therapy and the understanding involved of cancer therapy have led to an enhanced focus of the PI3-k/Akt/mTOR pathway as a potential area of targeting including pan and isoform-specific PI3-K inhibitors, Akt blockade, and mTOR suppression. The multitude, expanding roles, and varying clinical trials of these inhibitors have led to an increase in knowledge and availability for current and future studies. In this review, we provide a review of the literature with the aim to focus on potential targets for HCC therapies as well as an in depth focus on Akt inhibition.
Keywords: Akt inhibition, hepatocellular carcinoma, MK2206, PI3K/Akt/mTOR, sorafenib.
Anti-Cancer Agents in Medicinal Chemistry
Title:Potential Molecular Targeted Therapeutics: Role of PI3-K/Akt/mTOR Inhibition in Cancer
Volume: 16 Issue: 1
Author(s): Kevin M. Sokolowski, Steven Koprowski, Selvi Kunnimalaiyaan, Mariappan Balamurugan, T. Clark Gamblin and Muthusamy Kunnimalaiyaan
Affiliation:
Keywords: Akt inhibition, hepatocellular carcinoma, MK2206, PI3K/Akt/mTOR, sorafenib.
Abstract: Primary liver cancer is one of the most commonly occurring cancers worldwide. Hepatocellular carcinoma (HCC) represents the majority of primary liver cancer and is the 3rd most common cause of cancer-related deaths globally. Survival rates of patients with HCC are dependent upon early detection as concomitant liver dysfunction and advanced disease limits traditional therapeutic options such as resection or ablation. Unfortunately, at the time of diagnosis, most patients are not eligible for curative surgery and have a five-year relative survival rate less than 20%, leading to systemic therapy as the only option. Currently, sorafenib is the only approved systemic therapy; however, it has a limited survival advantage and low efficacy prompting alternative strategies. The inception of sorafenib for HCC systemic therapy and the understanding involved of cancer therapy have led to an enhanced focus of the PI3-k/Akt/mTOR pathway as a potential area of targeting including pan and isoform-specific PI3-K inhibitors, Akt blockade, and mTOR suppression. The multitude, expanding roles, and varying clinical trials of these inhibitors have led to an increase in knowledge and availability for current and future studies. In this review, we provide a review of the literature with the aim to focus on potential targets for HCC therapies as well as an in depth focus on Akt inhibition.
Export Options
About this article
Cite this article as:
Sokolowski M. Kevin, Koprowski Steven, Kunnimalaiyaan Selvi, Balamurugan Mariappan, Gamblin Clark T. and Kunnimalaiyaan Muthusamy, Potential Molecular Targeted Therapeutics: Role of PI3-K/Akt/mTOR Inhibition in Cancer, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (1) . https://dx.doi.org/10.2174/1871520615666150716104408
DOI https://dx.doi.org/10.2174/1871520615666150716104408 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Melatonin Regulates Angiogenic and Inflammatory Proteins in MDA-MB-231 Cell Line and in Co-culture with Cancer-associated Fibroblasts
Anti-Cancer Agents in Medicinal Chemistry Nuclear Receptor SHP as a Potential Therapeutic Target for Liver Cancer
Current Cancer Therapy Reviews Analgesic Considerations for Liver Transplantation Patients
Current Clinical Pharmacology Molecular Modeling Applied to Anti-Cancer Drug Development
Anti-Cancer Agents in Medicinal Chemistry Advances of Phenoxazines: Synthesis, Reactivity and Their Medicinal Applications
Current Medicinal Chemistry Global Gene Expression in Classification, Pathogenetic Understanding and Identification of Therapeutic Targets in Acute Myeloid Leukemia
Current Pharmaceutical Biotechnology Vinorelbine in the Treatment of Non-Small Cell Lung Cancer
Current Medicinal Chemistry Clinical Significance of Breast Cancer Resistance Protein/ABCG2 in the Management of Malignancy
Clinical Cancer Drugs MicroRNA Expression in Coronary Artery Disease
MicroRNA Paraneoplastic Pemphigus: Autoimmune-Cancer Nexus in the Skin
Anti-Cancer Agents in Medicinal Chemistry Autophagy Driven Extracellular Vesicles in the Leukaemic Microenvironment
Current Cancer Drug Targets Strategies Targeting DNA Topoisomerase I in Cancer Chemotherapy: Camptothecins, Nanocarriers for Camptothecins, Organic Non-Camptothecin Compounds and Metal Complexes
Current Drug Targets Lessons we Learned from High-Throughput and Top-Down Systems Biology Analyses about Glioma Stem Cells
Current Pharmaceutical Design Heterocyclic Curcumin Derivatives of Pharmacological Interest: Recent Progress
Current Topics in Medicinal Chemistry Development of Small-Molecule Inhibitors of Raf
Recent Patents on Anti-Infective Drug Discovery Mitophagy in Carcinogenesis and Tumour Progression- A New Paradigm with Emerging Importance
Anti-Cancer Agents in Medicinal Chemistry Biosafety of Onco-Retroviral Vectors
Current Gene Therapy Context-dependent Action of Transforming Growth Factor β Family Members on Normal and Cancer Stem Cells
Current Pharmaceutical Design Formulation Optimization of Etoposide Loaded PLGA Nanoparticles by Double Factorial Design and their Evaluation
Current Drug Delivery Functionalized Silver Nanoparticles for Sensing, Molecular Imaging and Therapeutic Applications
Current Nanomedicine