Signal Transduction Pathways of the Epidermal Growth Factor Receptor in Colorectal Cancer and their Inhibition by Small Molecules

Autoren

T Efferth

DOI

10.2174/092986712803988884

ISSN

0929-8673

Ausgabe der Veröffentlichung

33

Zeitschrift

Current Medicinal Chemistry

Sprache

en

Paginierung

5735 - 5744

Datum der Veröffentlichung

2012

Status

Published

Herausgeber

Bentham Science Publishers Ltd.

Herausgeber URL

http://dx.doi.org/10.2174/092986712803988884

Datum der Datenerfassung

2015

Titel

Signal Transduction Pathways of the Epidermal Growth Factor Receptor in Colorectal Cancer and their Inhibition by Small Molecules

Ausgabe der Zeitschrift

19

Data source: Crossref

Abstract

While prognostic factors can help to classify the standard risk of subpopulations of patients with the same tumor entity, it is still not possible to predict the response of individual patients to specific therapies. The reason for such wide variation in cancer therapy responses remains largely unknown. The field of chemotherapy is currently undergoing a paradigm shift from classical cytotoxic chemotherapy to targeted therapy in order to kill tumor cells more efficiently with fewer side effects on normal tissue. In the present review, we focus on colorectal carcinoma, which is one of the most frequent tumor types worldwide and represents a leading cause of cancer-related deaths. The signaling pathways downstream of epidermal growth factor receptor (EGFR) are central to the biology of colorectal cancer. A considerable achievement during the past years was the development of targeted therapies against EGFR using monoclonal antibodies and small molecule inhibitors. Two major pathways mediate signal transduction through EGFR: the RAS/RAF/MAPK/ERK and the PI3K/AKT/ PTEN/mTOR pathways. Sometimes, predictive biomarkers can provide information on the expected response of tumors to standard chemotherapy. Such molecular markers for EGFR-targeted treatment have been described. However, disease progression and resistance towards EGFR-directed drugs frequently develop due to mutations in genes downstream of EGFR. In this review, we describe the mechanisms by which colorectal cancers gain resistance against EGFR-targeted therapies as well as strategies to bypass mutationinduced resistance in these two signaling pathways.

Addresses

Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany. efferth@uni-mainz.de

Autoren

T Efferth
T Efferth

DOI

10.2174/092986712803988884

eISSN

1875-533X

Externe Identifier

PubMed Identifier: 23033949

Open access

false

ISSN

0929-8673

Ausgabe der Veröffentlichung

33

Zeitschrift

Current medicinal chemistry

Schlüsselwörter

Colon
Rectum
Animals
Humans
Colorectal Neoplasms
Antineoplastic Agents
Signal Transduction
Drug Resistance, Neoplasm
Small Molecule Libraries
Molecular Targeted Therapy
ErbB Receptors

Sprache

eng

Medium

Print

Paginierung

5735 - 5744

Datum der Veröffentlichung

2012

Status

Published

Datum der Datenerfassung

2012

Titel

Signal transduction pathways of the epidermal growth factor receptor in colorectal cancer and their inhibition by small molecules.

Sub types

Review
Journal Article

Ausgabe der Zeitschrift

19

Data source: Europe PubMed Central

Abstract

While prognostic factors can help to classify the standard risk of subpopulations of patients with the same tumor entity, it is still not possible to predict the response of individual patients to specific therapies. The reason for such wide variation in cancer therapy responses remains largely unknown. The field of chemotherapy is currently undergoing a paradigm shift from classical cytotoxic chemotherapy to targeted therapy in order to kill tumor cells more efficiently with fewer side effects on normal tissue. In the present review, we focus on colorectal carcinoma, which is one of the most frequent tumor types worldwide and represents a leading cause of cancer-related deaths. The signaling pathways downstream of epidermal growth factor receptor (EGFR) are central to the biology of colorectal cancer. A considerable achievement during the past years was the development of targeted therapies against EGFR using monoclonal antibodies and small molecule inhibitors. Two major pathways mediate signal transduction through EGFR: the RAS/RAF/MAPK/ERK and the PI3K/AKT/ PTEN/mTOR pathways. Sometimes, predictive biomarkers can provide information on the expected response of tumors to standard chemotherapy. Such molecular markers for EGFR-targeted treatment have been described. However, disease progression and resistance towards EGFR-directed drugs frequently develop due to mutations in genes downstream of EGFR. In this review, we describe the mechanisms by which colorectal cancers gain resistance against EGFR-targeted therapies as well as strategies to bypass mutationinduced resistance in these two signaling pathways.

Date of acceptance

2012

Autoren

T Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/23033949

DOI

10.2174/092986712803988884

eISSN

1875-533X

Ausgabe der Veröffentlichung

33

Zeitschrift

Curr Med Chem

Schlüsselwörter

Animals
Antineoplastic Agents
Colon
Colorectal Neoplasms
Drug Resistance, Neoplasm
ErbB Receptors
Humans
Molecular Targeted Therapy
Rectum
Signal Transduction
Small Molecule Libraries

Sprache

eng

Country

United Arab Emirates

Paginierung

5735 - 5744

PII

CMC-EPUB-20121001-5

Datum der Veröffentlichung

2012

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2013

Titel

Signal transduction pathways of the epidermal growth factor receptor in colorectal cancer and their inhibition by small molecules.

Sub types

Journal Article
Review

Ausgabe der Zeitschrift

19

Data source: PubMed

Signal Transduction Pathways of the Epidermal Growth Factor Receptor in Colorectal Cancer and their Inhibition by Small Molecules

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