Limits...
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

EGFR signaling pathway (reprinted with permission from BioCarta Pathways. All rights reserved).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3472558&req=5

fig1: EGFR signaling pathway (reprinted with permission from BioCarta Pathways. All rights reserved).

Mentions: The ErbB family is composed of 4 transmembrane receptors that interact with each other: EGFR/ErbB1/Her1, ErbB2/Her2/neu, ErbB3/Her3, and ErbB4/Her4 [3–5]. This interaction can result in either homodimerization or heterodimerization. Following dimerization, the intracellular tyrosine kinase portion is phosphorylated leading to downstream activation of complex interacting signaling pathways which include the Ras/Raf/MEK/ERK and the Ras/PI13 K/PTEN//AKT/mTOR pathways [5]. These pathways have been shown to regulate cellular replication, invasion, cellular repair, protection from insult, and induction of apoptosis. As diagrammed in Figure 1, signaling is thought to operate via both vertical and horizontal pathways. As intracellular signaling is found to be a vastly complex network, there is increasing rationale to target more than one signaling pathway or multiple targets within a single pathway in order to effectively regulate cancer. The design of an anticancer therapy employing an inhibitor of EGFR function was hypothesis-driven, based on knowledge available in the early 1980s [6]. EGFR and the Src oncogene product were shown to have the novel enzymatic activity of a tyrosine kinase [6]. Subsequent studies established that EGFR was a cellular oncogene and demonstrated that high levels of EGFR correlated with poorer prognosis in solid tumors [6]. Preclinical studies hypothesized that blockade of the EGFR binding sites with an “antireceptor” monoclonal antibody (mAb) would lead to the inhibition of cell growth, thereby making it an effective anticancer therapy [6].


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

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

EGFR signaling pathway (reprinted with permission from BioCarta Pathways. All rights reserved).
© Copyright Policy
Related In: Results  -  Collection

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

fig1: EGFR signaling pathway (reprinted with permission from BioCarta Pathways. All rights reserved).
Mentions: The ErbB family is composed of 4 transmembrane receptors that interact with each other: EGFR/ErbB1/Her1, ErbB2/Her2/neu, ErbB3/Her3, and ErbB4/Her4 [3–5]. This interaction can result in either homodimerization or heterodimerization. Following dimerization, the intracellular tyrosine kinase portion is phosphorylated leading to downstream activation of complex interacting signaling pathways which include the Ras/Raf/MEK/ERK and the Ras/PI13 K/PTEN//AKT/mTOR pathways [5]. These pathways have been shown to regulate cellular replication, invasion, cellular repair, protection from insult, and induction of apoptosis. As diagrammed in Figure 1, signaling is thought to operate via both vertical and horizontal pathways. As intracellular signaling is found to be a vastly complex network, there is increasing rationale to target more than one signaling pathway or multiple targets within a single pathway in order to effectively regulate cancer. The design of an anticancer therapy employing an inhibitor of EGFR function was hypothesis-driven, based on knowledge available in the early 1980s [6]. EGFR and the Src oncogene product were shown to have the novel enzymatic activity of a tyrosine kinase [6]. Subsequent studies established that EGFR was a cellular oncogene and demonstrated that high levels of EGFR correlated with poorer prognosis in solid tumors [6]. Preclinical studies hypothesized that blockade of the EGFR binding sites with an “antireceptor” monoclonal antibody (mAb) would lead to the inhibition of cell growth, thereby making it an effective anticancer therapy [6].

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