Role of genetic polymorphisms and mutations in colorectal cancer therapy (Review)

Marco Aiello, Nadia Vella, Calogero Cannavò, Aurora Scalisi, Demetrios A. Spandidos, Giuseppe Toffoli, Angela Buonadonna, Massimo Libra, Franca Stivala

Research output: Contribution to journalArticle

Abstract

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 In a related vein, our recent unpublished data show that the VEGF C936T polymorphism may increase the risk of DVP in cancer patients.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.

Original languageEnglish
Pages (from-to)203-208
Number of pages6
JournalMolecular Medicine Reports
Volume4
Issue number2
DOIs
Publication statusPublished - Mar 2011

Fingerprint

Genetic Polymorphisms
Polymorphism
Colorectal Neoplasms
Mutation
oxaliplatin
irinotecan
Chemotherapy
Therapeutics
Monoclonal Antibodies
Fluorouracil
Colonic Neoplasms
Vascular Endothelial Growth Factor A
Toxicity
Neoplasms
Biotransformation
Combination Drug Therapy
Bilirubin
Epidermal Growth Factor Receptor
Metabolism
Venous Thrombosis

Keywords

  • Biological therapy
  • Colorectal cancer
  • Gene polymorphisms

ASJC Scopus subject areas

  • Biochemistry
  • Cancer Research
  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Oncology

Cite this

Aiello, M., Vella, N., Cannavò, C., Scalisi, A., Spandidos, D. A., Toffoli, G., ... Stivala, F. (2011). Role of genetic polymorphisms and mutations in colorectal cancer therapy (Review). Molecular Medicine Reports, 4(2), 203-208. https://doi.org/10.3892/mmr.2010.408

Role of genetic polymorphisms and mutations in colorectal cancer therapy (Review). / Aiello, Marco; Vella, Nadia; Cannavò, Calogero; Scalisi, Aurora; Spandidos, Demetrios A.; Toffoli, Giuseppe; Buonadonna, Angela; Libra, Massimo; Stivala, Franca.

In: Molecular Medicine Reports, Vol. 4, No. 2, 03.2011, p. 203-208.

Research output: Contribution to journalArticle

Aiello, M, Vella, N, Cannavò, C, Scalisi, A, Spandidos, DA, Toffoli, G, Buonadonna, A, Libra, M & Stivala, F 2011, 'Role of genetic polymorphisms and mutations in colorectal cancer therapy (Review)', Molecular Medicine Reports, vol. 4, no. 2, pp. 203-208. https://doi.org/10.3892/mmr.2010.408
Aiello, Marco ; Vella, Nadia ; Cannavò, Calogero ; Scalisi, Aurora ; Spandidos, Demetrios A. ; Toffoli, Giuseppe ; Buonadonna, Angela ; Libra, Massimo ; Stivala, Franca. / Role of genetic polymorphisms and mutations in colorectal cancer therapy (Review). In: Molecular Medicine Reports. 2011 ; Vol. 4, No. 2. pp. 203-208.
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