Mutant Cell Surface Receptors as Targets for Individualized Cancer Diagnosis and Therapy

Authors: Becker K.Friedrich; Hofler H.

Source: Current Cancer Drug Targets, Volume 1, Number 2, August 2001 , pp. 121-128(9)

Publisher: Bentham Science Publishers

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Abstract:

The catalogue of gene alterations in human cancer is growing rapidly. Alterations in specific genes that play important roles in diverse cellular functions such as cell adhesion, signal transduction, differentiation, development or DNA-repair have been identified. Cancer-associated mutant cell surface molecules are very attractive candidates to target tumor cells because they offer the possibility of minimizing toxic effects to non-tumor cells. The cell adhesion molecule E-cadherin has been shown to play a major role in determining which of the two subtypes of gastric cancer, diffuse or intestinal type, develops. E-cadherin gene mutations typically affect the extracellular portion of the homophilic receptor and are frequently found in patients with diffuse-type tumors. Cancer-specific monoclonal antibodies against the E-cadherin mutational hot spot region are now available. In cell culture and in animal studies we have shown that mutation-specific antibodies exclusively target cells expressing abnormal E-cadherin. Those cells expressing the normal protein were not affected, demonstrating the specificity of our approach. After linking to toxins, drugs or radiolabeled mutation-specific antibodies could serve as very specific agents to treat small tumor deposits. Patients for this novel individualized cancer therapy can be identified within a day using routine immunohistochemistry of biopsies.

Keywords: Mutant Cell Surface; E-cadherin; B-cell marker CD20; Germline Mutations; dominant-negative manner

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1568009013334205

Publication date: 2001-08-01

More about this publication?

Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes, genes.
Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cancer.
As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.

Mutant Cell Surface Receptors as Targets for Individualized Cancer Diagnosis and Therapy

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