Abstract
RAS family proteins are important signaling molecules that regulate cell growth, survival and differentiation by coupling receptor activation to downstream effector pathways. Three distinct genes encode for the three different proteins H-, K-, and N- RAS. These proteins share high sequence homology, particularly at the N-Terminal domain. Among them, K-RAS is one of the most frequently mutated in human cancer. The majority of the mutations present in K-RAS are at codon 12 (from 80 to 100%) followed by codon 13 and 61. In all cases, aminoacid change leads to a constitutively activated protein.
K-RAS mutations have a role in tumor development as well as in tumor progression and resistance. Despite the various studies which have been published, the prognostic and predictive role of K-RAS mutations is still under debate. Keeping in mind that the glycine present at position 12 can be substituted by valine, aspartic acid or cysteine, it could be well understood that each different substitution plays a different role in K-RAS-dependent processes.
The present article focuses on the molecular and biological characteristics of K-RAS protein, its role in NSCLC tumor development and progression. We also present an overview of the preclinical models both in vitro and in vivo available to determine the role of K-RAS in tumor progression and response to treatment and on the recent results obtained in this field. Finally, we have considered the impact of KRAS mutations in clinical practice, analyzing the different recent trials that have taken into consideration K-RAS.
Keywords: K-RAS, non-small-cell-lung cancer, mutation, animal model, synthetic lethality, cell response, prognosis.
Current Pharmaceutical Design
Title:Across the Universe of K-Ras Mutations in Non-Small-Cell-Lung Cancer
Volume: 20 Issue: 24
Author(s): Sheila Piva, Monica Ganzinelli, Marina Chiara Garassino, Elisa Caiola, Gabriella Farina, Massimo Broggini and Mirko Marabese
Affiliation:
Keywords: K-RAS, non-small-cell-lung cancer, mutation, animal model, synthetic lethality, cell response, prognosis.
Abstract: RAS family proteins are important signaling molecules that regulate cell growth, survival and differentiation by coupling receptor activation to downstream effector pathways. Three distinct genes encode for the three different proteins H-, K-, and N- RAS. These proteins share high sequence homology, particularly at the N-Terminal domain. Among them, K-RAS is one of the most frequently mutated in human cancer. The majority of the mutations present in K-RAS are at codon 12 (from 80 to 100%) followed by codon 13 and 61. In all cases, aminoacid change leads to a constitutively activated protein.
K-RAS mutations have a role in tumor development as well as in tumor progression and resistance. Despite the various studies which have been published, the prognostic and predictive role of K-RAS mutations is still under debate. Keeping in mind that the glycine present at position 12 can be substituted by valine, aspartic acid or cysteine, it could be well understood that each different substitution plays a different role in K-RAS-dependent processes.
The present article focuses on the molecular and biological characteristics of K-RAS protein, its role in NSCLC tumor development and progression. We also present an overview of the preclinical models both in vitro and in vivo available to determine the role of K-RAS in tumor progression and response to treatment and on the recent results obtained in this field. Finally, we have considered the impact of KRAS mutations in clinical practice, analyzing the different recent trials that have taken into consideration K-RAS.
Export Options
About this article
Cite this article as:
Piva Sheila, Ganzinelli Monica, Garassino Chiara Marina, Caiola Elisa, Farina Gabriella, Broggini Massimo and Marabese Mirko, Across the Universe of K-Ras Mutations in Non-Small-Cell-Lung Cancer, Current Pharmaceutical Design 2014; 20 (24) . https://dx.doi.org/10.2174/13816128113196660761
DOI https://dx.doi.org/10.2174/13816128113196660761 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Imaging of Integrins as Biomarkers for Tumor Angiogenesis
Current Pharmaceutical Design Flt3 Receptor Tyrosine Kinase as a Drug Target in Leukemia
Current Pharmaceutical Design Crocetin, a Carotenoid Derivative, Inhibits VEGF-Induced Angiogenesis via Suppression of p38 Phosphorylation
Current Neurovascular Research Agents Targeting Ras Signaling Pathway
Current Pharmaceutical Design Review: The Role of MOP and DOP Receptors in Treatment of Diarrheapredominant Irritable Bowel Syndrome
Mini-Reviews in Medicinal Chemistry Impact on DNA Methylation in Cancer Prevention and Therapy by Bioactive Dietary Components
Current Medicinal Chemistry Targeting Tyrosine Kinase Receptors in Hepatocellular Carcinoma
Current Cancer Drug Targets Alzheimer’s Disease and Molecular Chaperones: Current Knowledge and the Future of Chaperonotherapy
Current Pharmaceutical Design Gallic Acid-Phospholipid Complex: Drug Incorporation and Physicochemical Characterization
Letters in Drug Design & Discovery Targeted Gene Therapy for Ovarian Cancer
Current Gene Therapy Personalized Peptide Vaccine for Treatment of Advanced Cancer
Current Medicinal Chemistry Cytokines as Novel Therapeutic Agents for Neuroinflammatory Disorders: A Role for Interferon-β in the Treatment of Multiple Sclerosis
Current Medicinal Chemistry - Central Nervous System Agents Nanocarriers Conjugated with Cell Penetrating Peptides: New Trojan Horses by Modern Ulysses
Current Pharmaceutical Biotechnology Methodological Aspects and Applications of In Vivo Imaging of Apoptosis in Oncology: An Illustrative Review
Current Medical Imaging Versatile and Valuable Utilization of Amidohydrolase L-glutaminase in Pharma and Food industries: A Review
Current Drug Metabolism Insights into Angiogenesis in Non-Small Cell Lung Cancer: Molecular Mechanisms, Polymorphic Genes, and Targeted Therapies
Recent Patents on Anti-Cancer Drug Discovery Targeting Antioxidants to Mitochondria: A Potential New Therapeutic Strategy for Cardiovascular Diseases
Current Pharmaceutical Design Nanobiotechnology: An Efficient Approach to Drug Delivery of Unstable Biomolecules
Current Protein & Peptide Science Sulfur Containing Acridine Derivatives in Preclinical Studies with Cancer Cell Lines
Current Medicinal Chemistry Glioblastoma Multiforme and its Cell Interruption
Current Cancer Therapy Reviews