Abstract
Constitutive activation of the EGFR/RAS/PI3K cell-signaling pathway that may occur through molecular aberrations in core pathway components occurs in many solid tumours, including colorectal cancer(CRC), non-small-cell lung cancer(NSCLC) and breast cancer. Predictive biomarkers of response to therapeutics targeting this pathway are necessary to select patients more likely to respond, and importantly, to avoid treating patients likely to suffer a worse outcome with therapy compared to standard of care. Determination of EGFR by immunohistochemistry(IHC) is not strongly predictive of response to EGFR-targeted therapy in CRC and NSCLC. EGFR gene mutations in the tyrosine kinase(TK) domain are predictive of response to EGFR tyrosine kinase inhibitors(TKIs) in NSCLC, and the acquisition of a point mutation in an amino acid in an adjacent area, T790M, is predictive of resistance. However, novel irreversible EGFR inhibitors such as BIBW-2992 and HKI-272 may retain activity in tumours with T790M mutations. It is well established in CRC that mutations in KRAS are predictive of resistance to EGFR pathway inhibition, and may predict for a poorer outcome with therapy. Other potentially useful biomarkers of resistance to EGFR-targeted therapy in the process of clinical validation include mutations in BRAF, PTEN loss and PIK3CA mutations, nuclear factor-kappa beta(NF-KB) pathway activity, and expression of alternative EGFR ligands. Functional genomics elucidation of drug resistance pathways using RNA interference(RNAi) techniques may provide novel therapeutic approaches in disease resistant to EGFR pathway targeting and accelerate predictive biomarker development.
Keywords: Predictive molecular markers, epidermal growth factor receptor(EGFR), RAS, phosphoinositide 3-kinase(PI3K), response, resistance, targeted therapy, biomarker.
Current Cancer Drug Targets
Title: Predictive Molecular Markers of Response to Epidermal Growth Factor Receptor(EGFR) Family-Targeted Therapies
Volume: 10 Issue: 8
Author(s): Sarah Barton, Naureen Starling and Charles Swanton
Affiliation:
Keywords: Predictive molecular markers, epidermal growth factor receptor(EGFR), RAS, phosphoinositide 3-kinase(PI3K), response, resistance, targeted therapy, biomarker.
Abstract: Constitutive activation of the EGFR/RAS/PI3K cell-signaling pathway that may occur through molecular aberrations in core pathway components occurs in many solid tumours, including colorectal cancer(CRC), non-small-cell lung cancer(NSCLC) and breast cancer. Predictive biomarkers of response to therapeutics targeting this pathway are necessary to select patients more likely to respond, and importantly, to avoid treating patients likely to suffer a worse outcome with therapy compared to standard of care. Determination of EGFR by immunohistochemistry(IHC) is not strongly predictive of response to EGFR-targeted therapy in CRC and NSCLC. EGFR gene mutations in the tyrosine kinase(TK) domain are predictive of response to EGFR tyrosine kinase inhibitors(TKIs) in NSCLC, and the acquisition of a point mutation in an amino acid in an adjacent area, T790M, is predictive of resistance. However, novel irreversible EGFR inhibitors such as BIBW-2992 and HKI-272 may retain activity in tumours with T790M mutations. It is well established in CRC that mutations in KRAS are predictive of resistance to EGFR pathway inhibition, and may predict for a poorer outcome with therapy. Other potentially useful biomarkers of resistance to EGFR-targeted therapy in the process of clinical validation include mutations in BRAF, PTEN loss and PIK3CA mutations, nuclear factor-kappa beta(NF-KB) pathway activity, and expression of alternative EGFR ligands. Functional genomics elucidation of drug resistance pathways using RNA interference(RNAi) techniques may provide novel therapeutic approaches in disease resistant to EGFR pathway targeting and accelerate predictive biomarker development.
Export Options
About this article
Cite this article as:
Barton Sarah, Starling Naureen and Swanton Charles, Predictive Molecular Markers of Response to Epidermal Growth Factor Receptor(EGFR) Family-Targeted Therapies, Current Cancer Drug Targets 2010; 10 (8) . https://dx.doi.org/10.2174/156800910793357925
DOI https://dx.doi.org/10.2174/156800910793357925 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
WNT Signaling in Stem Cell Biology and Regenerative Medicine
Current Drug Targets Can Targeting the Incretin Pathway Dampen RAGE-Mediated Events in Diabetic Nephropathy?
Current Drug Targets Pathogenesis of Type 1 Diabetes: Regulation of Adhesion Molecules and Immune Cell Trafficking
Current Immunology Reviews (Discontinued) Therapeutic Targeting of NLRP3 Inflammasomes by Natural Products and Pharmaceuticals: A Novel Mechanistic Approach for Inflammatory Diseases
Current Medicinal Chemistry State of the Art of Biochemical Markers in Metastatic Bone Disease and the Role of Bisphosphonates as Therapeutic Agents
Current Pharmaceutical Analysis Synthesis of Metronidazole Derivatives Containing Pyridine Ring and Anticancer Activity
Letters in Organic Chemistry In Vivo Inhibition of Proteasome Activity and Tumour Growth by Murraya koenigii Leaf Extract in Breast Cancer Xenografts and by Its Active Flavonoids in Breast Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Deciphering the Role of Forkhead Transcription Factors in Cancer Therapy
Current Drug Targets Bortezomib: A New Pro-Apoptotic Agent in Cancer Treatment
Current Cancer Drug Targets Synthesis and Antiproliferative Activity of New Polyoxo 2-Benzyl-2,3- dihydrobenzofurans and Their Related Compounds
Letters in Drug Design & Discovery Adenosine Deaminase in the Modulation of Immune System and its Potential as a Novel Target for Treatment of Inflammatory Disorders
Current Drug Targets Intracellular Expression of Inflammatory Proteins S100A8 and S100A9 Leads to Epithelial-mesenchymal Transition and Attenuated Aggressivity of Breast Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Drug Resistance: Challenges to Effective Therapy
Current Cancer Drug Targets Polymer Particulates in Drug Delivery
Current Pharmaceutical Design Editorial [Hot Topic: Targeting Mast Cells and Basophils in Allergy and Beyond: Emerging Concepts (Executive Guest Editor: Petr Heneberg)]
Current Pharmaceutical Design TSC-22 (TGF-β Stimulated Clone-22): A Novel Molecular Target for Differentiation-Inducing Therapy in Salivary Gland Cancer
Current Cancer Drug Targets Anti-Inflammatory Approaches that Target the Chemokine Network
Recent Patents on Inflammation & Allergy Drug Discovery Perturbation of HSP Network in MCF-7 Breast Cancer Cell Line Triggers Inducible HSP70 Expression and Leads to Tumor Suppression
Anti-Cancer Agents in Medicinal Chemistry Nanomedicines for Brain Targeting: A Patent Review
Recent Patents on Nanomedicine Advances in Photodynamic Therapy of Cancer
Current Cancer Therapy Reviews