Exploration of synthetic lethal interactions as cancer drug targets

In cancer research the quest continues to identify the Achilles heel of cancer. The ideal cancer drug targets are those that are essential in tumor cells but not in normal cells. Such targets are defined as cancer-specific vulnerabilities or as synthetic lethal interactions with cancer-specific gene...

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Vydáno v:Future oncology (London, England) Ročník 6; číslo 11; s. 1789 - 1802
Hlavní autoři: Kuiken, Hendrik J, Beijersbergen, Roderick L
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Future Medicine Ltd 01.11.2010
Témata:
(non)oncogene addiction
Animals
Antimitotic agents
Antineoplastic agents
chemical-genetic
Development and progression
Drug interactions
Drug Screening Assays, Antitumor - methods
Drug therapy
Genes, ras - physiology
Genetic Testing
Health aspects
Humans
Molecular Targeted Therapy
Neoplasms - genetics
Neoplasms - therapy
network addiction
RAS
RNA Interference
RNAi
screen
shRNA
siRNA
synthetic lethal interaction
Tumors
Netherlands
ISSN:1479-6694, 1744-8301, 1744-8301
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Popis
Shrnutí:In cancer research the quest continues to identify the Achilles heel of cancer. The ideal cancer drug targets are those that are essential in tumor cells but not in normal cells. Such targets are defined as cancer-specific vulnerabilities or as synthetic lethal interactions with cancer-specific genetic lesions. The search for synthetic lethal interactions focuses on proteins that are frequently mutated but elude pharmacological inhibition, for example, RAS, or proteins that are lost in cancer cells and by definition cannot be targeted, such as the tumor suppressor genes , and . These genetic interactions could yield alternative, effective targets for cancer treatment. However, it remains very difficult to predict or extrapolate these synthetic lethal interactions based on existing knowledge. With the discovery of RNAi, unbiased large-scale functional genomic screens for the identification of such targets have become possible potentially leading to major advances in the treatment of cancers. In this review we will discuss the biological basis of synthetic lethal interactions in relation to existing targeted therapeutics, lessons taught by targeted therapeutics already used in the clinic and the implementation of RNAi as tool to identify such synthetic lethal interactions.
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ISSN:1479-6694
1744-8301
1744-8301
DOI:10.2217/fon.10.131