TY - JOUR
T1 - Histological and genetic markers for non-small-cell lung cancer
T2 - Customizing treatment based on individual tumor biology
AU - Adams, Val R.
AU - Harvey, R. Donald
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Purpose. To describe how molecular and genetic markers influence the response to therapy in patients with advanced non-small-cell lung cancer (NSCLC). Summary. Cisplatin resistance has been associated with high rates of expression of endonucleases, a family of DNA repair proteins that includes EHCC1 and BRCA1. Gemcitabine is thought to produce its antitumor effects by several mechanisms, including inhibition of ribonucleotide conversion to deoxyribonucleotide through the inactivation of ribonucleotide reductase. One type of gemcitabine resistance occurs when the inactivation of ribonucleotide reductase decreases, which correlates with increased expression of the Ml subunit of ribonucleotide reducta se. Taxanes produce their anti-tumor effects by binding to and stabilizing intracellular microtubules, which are necessary for DNA replication and cell division. High expression of β-tubulin III, a microtubule subunit with low taxane binding affinity, appears to confer resistance to taxane therapy. High expression of thymidylate synthase, an enzyme that is important in purine synthesis and DNA replication, has been associated with decreased response to uracil antimetabolites, and may also be an important prognostic factor in patients receiving pemetrexed. The epidermal growth factor receptor (EGFR) is a cell-surface receptor with an intracellular tyrosine kinase domain that is thought to modulate numerous cellular functions that contribute to tumorigenicity, tumor invasiveness, and resistance to therapy. Recent clinical trials have demonstrated that treatment response to small-molecule and monoclonal antibody inhibitors of EGFR is greatest for patients who have a higher EGFR gene copy number. Conclusion. Several genetic, molecular, and histological markers may affect treatment response in patients with NSCLC Evaluating patients for such markers is important not only for treatment efficacy, but also to improve safety and tolerability by avoiding exposure to treatments that are unlikely to produce significant benefits. Nearly all of the available information regarding the predictive value of these markers has been derived from retrospective studies. Prospective clinical trials are important to validate marker evaluation methodology and the prospective utility of biomarkers in clinical decision making.
AB - Purpose. To describe how molecular and genetic markers influence the response to therapy in patients with advanced non-small-cell lung cancer (NSCLC). Summary. Cisplatin resistance has been associated with high rates of expression of endonucleases, a family of DNA repair proteins that includes EHCC1 and BRCA1. Gemcitabine is thought to produce its antitumor effects by several mechanisms, including inhibition of ribonucleotide conversion to deoxyribonucleotide through the inactivation of ribonucleotide reductase. One type of gemcitabine resistance occurs when the inactivation of ribonucleotide reductase decreases, which correlates with increased expression of the Ml subunit of ribonucleotide reducta se. Taxanes produce their anti-tumor effects by binding to and stabilizing intracellular microtubules, which are necessary for DNA replication and cell division. High expression of β-tubulin III, a microtubule subunit with low taxane binding affinity, appears to confer resistance to taxane therapy. High expression of thymidylate synthase, an enzyme that is important in purine synthesis and DNA replication, has been associated with decreased response to uracil antimetabolites, and may also be an important prognostic factor in patients receiving pemetrexed. The epidermal growth factor receptor (EGFR) is a cell-surface receptor with an intracellular tyrosine kinase domain that is thought to modulate numerous cellular functions that contribute to tumorigenicity, tumor invasiveness, and resistance to therapy. Recent clinical trials have demonstrated that treatment response to small-molecule and monoclonal antibody inhibitors of EGFR is greatest for patients who have a higher EGFR gene copy number. Conclusion. Several genetic, molecular, and histological markers may affect treatment response in patients with NSCLC Evaluating patients for such markers is important not only for treatment efficacy, but also to improve safety and tolerability by avoiding exposure to treatments that are unlikely to produce significant benefits. Nearly all of the available information regarding the predictive value of these markers has been derived from retrospective studies. Prospective clinical trials are important to validate marker evaluation methodology and the prospective utility of biomarkers in clinical decision making.
KW - Antibodies
KW - Antineoplastic agents
KW - Cisplatin
KW - Gemcitabine
KW - Genetics
KW - Lung neoplasms
KW - Mechanism of action
KW - Pemetrexed
KW - Resistance
KW - Taxanes
KW - Toxicity
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U2 - 10.2146/ajhp090456
DO - 10.2146/ajhp090456
M3 - Article
C2 - 20044377
AN - SCOPUS:73949094651
SN - 1079-2082
VL - 67
SP - S3-S9
JO - American Journal of Health-System Pharmacy
JF - American Journal of Health-System Pharmacy
IS - SUPPL. 1
ER -