Targeted Therapies in the Treatment of Colorectal Cancers

Alekshun, Todd J.; Garrett, Chris R.

doi:10.1177/107327480501200205

Cited by 33 publications

(20 citation statements)

References 32 publications

(20 reference statements)

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“…Both bind to the extracellular domain of EGFR, thereby acting as competitive antagonists of the natural ligands, EGF and transforming growth factor ␣ [45,46]. As a result, these mAbs block EGFR-mediated signaling, leading to G 1 cell cycle arrest as a result of hypophosphorylation of the retinoblastoma protein [47]. In addition, these mAbs induce downregulation of EGFR expression on the cell surface [45].…”

Section: Epidermal Growth Factor Receptor-targeted Antibodies: Cetuximentioning

confidence: 99%

A Mechanistic Perspective of Monoclonal Antibodies in Cancer Therapy Beyond Target-Related Effects

Strome¹,

Sausville²,

Mann

2007

The Oncologist

116

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After completing this course, the reader will be able to:1. Describe the relationship between antibody structure and effector function, and identify strategies for modifying antibody structure to enhance these functions.2. Explain how the efficacy of monoclonal antibodies in cancer therapy may occur via antibody-as well as targetrelated mechanisms.3. Discuss how the ability of monoclonal antibodies to activate immune-mediated effector functions differs across antibody isotypes.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTSeveral monoclonal antibodies are now in clinical use for cancer therapy, and many others are currently undergoing clinical evaluation. These agents offer unique specificity against key molecular targets on tumor cells or in the tumor microenvironment. The clinical efficacy of monoclonal antibodies is generally attributed to target-specific mechanisms resulting from neutralizing or inhibiting a growth factor or receptor that drives cell proliferation and tumor growth. Several targets, including CD20, human epidermal growth factor receptor 2, vascular endothelial growth factor, and epidermal growth factor receptor, have been validated in specific malignancies on the basis of monoclonal antibody efficacy. However, monoclonal antibodies also have the potential to activate immune-mediated effector functions, including antibody-dependent cellmediated cytotoxicity and complement-dependent cytotoxicity. These functions result from interactions involving the Fc domain of the antibody, and, consequently, may vary by antibody, isotype, and Fc modification, such as changes in glycosylation. Accordingly, all monoclonal antibodies directed against a given target should not be considered equivalent in their ability to stimulate immunemediated effector functions. The Oncologist

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Section: Epidermal Growth Factor Receptor-targeted Antibodies: Cetuximentioning

confidence: 99%

A Mechanistic Perspective of Monoclonal Antibodies in Cancer Therapy Beyond Target-Related Effects

Strome¹,

Sausville²,

Mann

2007

The Oncologist

116

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“…2 Kaplan-Meier survival curves of (a) time to progression (TTP) and of (b) overall survival (OS) zumab has a lower affinity for EGFR. The binding affinity constant (Km) has been reported to be 10 −8 M for nimotuzumab, 10 −10 M for cetuximab and 10 −11 M for panitumumab [5,21,22]. A recent study suggested nimotuzumab could bind to EGFR with transient monovalent binding on cells with low levels of EGFR [23].…”

Section: Discussionmentioning

confidence: 99%

A dose-escalation phase I trial of nimotuzumab, an antibody against the epidermal growth factor receptor, in patients with advanced solid malignancies

et al. 2010

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“…Severe anaphylaxis occurred in 2% of patients and acneiform rash in 80% [45]. Although the mechanism of the improved response in the combination arm is unclear, it may have been related to reduced irinotecan effux from malignant cells, induction of apoptosis or effects on DNA repair [46]. An interesting observation from the BOND-1 study was the observed association between high-grade skin reactions, response rate and TTP.…”

Section: Cetuximabmentioning

confidence: 94%

Biological therapy update in colorectal cancer

Sorscher¹

2007

Expert Opinion on Biological Therapy

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Colon and rectal cancer remain the second most common cause of cancer death in the US. Advances in the past 10 years have resulted in improved outcomes for patients. In addition to newer chemotherapeutics agents, the so-called 'targeted' or 'biological' therapies have improved survival in patients with metastatic disease. This review aims to summarize the mechanistic basis for the usefulness of these agents, the key clinical trials demonstrating their efficacy, and the studies now initiated with the hope of further incorporating their use in treating colon and rectal cancer.

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Targeted Therapies in the Treatment of Colorectal Cancers

Abstract: These dramatic successes have led to further clinical studies of targeted therapy in colorectal cancer, making it one of the most promising areas of cancer research.

Cited by 33 publications

References 32 publications

A Mechanistic Perspective of Monoclonal Antibodies in Cancer Therapy Beyond Target-Related Effects

A Mechanistic Perspective of Monoclonal Antibodies in Cancer Therapy Beyond Target-Related Effects

A dose-escalation phase I trial of nimotuzumab, an antibody against the epidermal growth factor receptor, in patients with advanced solid malignancies

Biological therapy update in colorectal cancer

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