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Antiepidermal growth factor receptor monoclonal antibodies: applications in colorectal cancer.

Azizi E, Kittai A, Kozuch P - Chemother Res Pract (2012)

Bottom Line: The role of the antiepidermal growth factor receptor (EGFR) pathway in tumorogenesis and tumor progression has been well defined.This paper will review the use of anti-EGFR monoclonal antibodies in the treatment of operable, as well as metastatic colorectal cancer both in the setting of KRAS mutation unselected patients and later in KRAS wild-type patients.Active investigations designed to further identify predictive biomarkers that may be potentially druggable are reviewed as well.

View Article: PubMed Central - PubMed

Affiliation: Beth Israel Medical Center, Phillips Ambulatory Care Center, Continuum Cancer Centers of New York, 10 Union Square East, Suite 4C, New York, NY, USA ; Section of Hematology/Oncology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.

ABSTRACT
Patients with metastatic colorectal cancer have a poor prognosis and present a challenge to clinicians. The role of the antiepidermal growth factor receptor (EGFR) pathway in tumorogenesis and tumor progression has been well defined. This paper will review the use of anti-EGFR monoclonal antibodies in the treatment of operable, as well as metastatic colorectal cancer both in the setting of KRAS mutation unselected patients and later in KRAS wild-type patients. Active investigations designed to further identify predictive biomarkers that may be potentially druggable are reviewed as well.

No MeSH data available.


Related in: MedlinePlus

Reprinted with permission from Erica A. Golemis, Ph. D. All rights reserved.
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fig2: Reprinted with permission from Erica A. Golemis, Ph. D. All rights reserved.

Mentions: There are two classes of EGFR antagonists currently in clinical use: anti-EGFR monoclonal antibodies and EGFR tyrosine kinase inhibitors (TKIs) [5] (Figure 2). Initial clinical trials of these agents did not assess subjects' tumors for the absence of KRAS mutations which have since been found to confer resistance to anti-EGFR mAbs. Restricting eligibility for clinical trial participation to only patients with wild-type KRAS (wtKRAS) CRC as opposed to mutated KRAS (mutKRAS) CRC has been a crucial step in optimizing the use of EGFR targeting mAbs. Cetuximab and panitumumab are the two anti-EGFR mAbs that have demonstrated clinical benefit and have gained FDA approval for the palliative treatment of chemotherapy resistant wtKRAS metastatic colorectal cancer (mCRC). Both mAbs bind to the extracellular domain of the cell receptor and inhibit dimerization, tyrosine kinase activation, and subsequent cell signal transduction [5].


Antiepidermal growth factor receptor monoclonal antibodies: applications in colorectal cancer.

Azizi E, Kittai A, Kozuch P - Chemother Res Pract (2012)

Reprinted with permission from Erica A. Golemis, Ph. D. All rights reserved.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472558&req=5

fig2: Reprinted with permission from Erica A. Golemis, Ph. D. All rights reserved.
Mentions: There are two classes of EGFR antagonists currently in clinical use: anti-EGFR monoclonal antibodies and EGFR tyrosine kinase inhibitors (TKIs) [5] (Figure 2). Initial clinical trials of these agents did not assess subjects' tumors for the absence of KRAS mutations which have since been found to confer resistance to anti-EGFR mAbs. Restricting eligibility for clinical trial participation to only patients with wild-type KRAS (wtKRAS) CRC as opposed to mutated KRAS (mutKRAS) CRC has been a crucial step in optimizing the use of EGFR targeting mAbs. Cetuximab and panitumumab are the two anti-EGFR mAbs that have demonstrated clinical benefit and have gained FDA approval for the palliative treatment of chemotherapy resistant wtKRAS metastatic colorectal cancer (mCRC). Both mAbs bind to the extracellular domain of the cell receptor and inhibit dimerization, tyrosine kinase activation, and subsequent cell signal transduction [5].

Bottom Line: The role of the antiepidermal growth factor receptor (EGFR) pathway in tumorogenesis and tumor progression has been well defined.This paper will review the use of anti-EGFR monoclonal antibodies in the treatment of operable, as well as metastatic colorectal cancer both in the setting of KRAS mutation unselected patients and later in KRAS wild-type patients.Active investigations designed to further identify predictive biomarkers that may be potentially druggable are reviewed as well.

View Article: PubMed Central - PubMed

Affiliation: Beth Israel Medical Center, Phillips Ambulatory Care Center, Continuum Cancer Centers of New York, 10 Union Square East, Suite 4C, New York, NY, USA ; Section of Hematology/Oncology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.

ABSTRACT
Patients with metastatic colorectal cancer have a poor prognosis and present a challenge to clinicians. The role of the antiepidermal growth factor receptor (EGFR) pathway in tumorogenesis and tumor progression has been well defined. This paper will review the use of anti-EGFR monoclonal antibodies in the treatment of operable, as well as metastatic colorectal cancer both in the setting of KRAS mutation unselected patients and later in KRAS wild-type patients. Active investigations designed to further identify predictive biomarkers that may be potentially druggable are reviewed as well.

No MeSH data available.


Related in: MedlinePlus