Linked Life Data

21468552

Source:http://linkedlifedata.com/resource/pubmed/id/21468552

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-4-6
pubmed:abstractText
Gene polymorphisms and mutations in various types of cancer may predict clinical response to chemotherapy and related toxicity, since they may affect the metabolism of the drugs commonly used in combination chemotherapy treatments. However, conflicting data have been generated on this subject. To elucidate this issue, this review discusses the clinical applications of several genetic polymorphisms in colorectal cancer patients treated with the most common agents alone or in combination. UDP-glucuronosyltransferase (UGT)1A1 is a conjugating biotransformation enzyme that plays a role in maintaining the levels of endogenous compounds (e.g., bilirubin) and in handling exogenous compounds, including carcinogens. It has been demonstrated that the UGT1A1*28 polymorphism plays a predictive role in patients administered an irinotecan-containing regimen. Polymorphisms in XPD (Lys751Gln), a member of the nucleotide excision repair pathway, negatively affect response to therapy, with oxaliplatin/5FU reducing the survival of the patient. A similar reaction has also been observed in patients with the XRCC1 Arg399Gln polymorphism, while patients with the GSTP1 Ile105Val polymorphism have an improved response to oxaliplatin/5FU therapy. Treatment with biological compounds such as cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, has been shown to be effective only in colon cancer patients with wild-type K-Ras. Fc polymorphisms are associated with progression-free survival in patients treated with cetuximab. Another monoclonal antibody useful in the treatment of colon cancer is bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF); however, in some cases bevacizumab may cause deep vein thrombosis (DVP). In a related vein, our recent unpublished data show that the VEGF C936T polymorphism may increase the risk of DVP in cancer patients. In conclusion, this review indicates that certain polymorphisms increase the effectiveness of certain drugs, while others greatly enhance their toxicity. The study of the genetic 'habitus' therefore appears to be crucial for the development of tailored therapy for cancer patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1791-3004
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
203-8
pubmed:meshHeading
pubmed:articleTitle
Role of genetic polymorphisms and mutations in colorectal cancer therapy (Review).
pubmed:affiliation
Department of Biomedical Sciences, University of Catania, Catania, Italy.
pubmed:publicationType
Journal Article, Review