TY - JOUR
T1 - Pharmacogenomics of platinum-based chemotherapy in NSCLC
AU - Hildebrandt, Michelle A.T.
AU - Gu, Jian
AU - Wu, Xifeng
N1 - Funding Information:
This work was supported by National Cancer Institute grants R01 CA111646 and P50 CA070907.
PY - 2009/7
Y1 - 2009/7
N2 - NSCLC is the leading cause of cancer-related death in the US. Patients with NSCLC are mostly treated with platinum-based chemotherapy, often in combination with radiation therapy. However, the development of chemo-resistance is a major hurdle limiting treatment success. In this review, we summarize the current understanding of the genetic factors modulating chemoresistance to platinum chemotherapeutics and their association with clinical outcomes for NSCLC patients. We focus on candidate pathways responsible for drug influx and efflux, metabolism and detoxification, DNA damage repair, and other downstream cellular processes that modulate the effect of platinum-based therapy. We also discuss the application of pathway-based polygenic and genome-wide approaches in identifying genetic factors involved in NSCLC clinical outcomes. Overall, current studies have shown that the effects of each individual polymorphism on clinical outcomes are modest suggesting that a more comprehensive approach that incorporates polygenetic, phenotypic, epidemiologic and clinical variables will be necessary to predict prognosis for NSCLC patients receiving platinum-based chemotherapeutics.
AB - NSCLC is the leading cause of cancer-related death in the US. Patients with NSCLC are mostly treated with platinum-based chemotherapy, often in combination with radiation therapy. However, the development of chemo-resistance is a major hurdle limiting treatment success. In this review, we summarize the current understanding of the genetic factors modulating chemoresistance to platinum chemotherapeutics and their association with clinical outcomes for NSCLC patients. We focus on candidate pathways responsible for drug influx and efflux, metabolism and detoxification, DNA damage repair, and other downstream cellular processes that modulate the effect of platinum-based therapy. We also discuss the application of pathway-based polygenic and genome-wide approaches in identifying genetic factors involved in NSCLC clinical outcomes. Overall, current studies have shown that the effects of each individual polymorphism on clinical outcomes are modest suggesting that a more comprehensive approach that incorporates polygenetic, phenotypic, epidemiologic and clinical variables will be necessary to predict prognosis for NSCLC patients receiving platinum-based chemotherapeutics.
KW - Carboplatin
KW - Chemotherapy
KW - Cisplatin
KW - Clinical outcomes
KW - NSCLC
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U2 - 10.1517/17425250902973711
DO - 10.1517/17425250902973711
M3 - Review article
C2 - 19442035
AN - SCOPUS:67650720782
SN - 1742-5255
VL - 5
SP - 745
EP - 755
JO - Expert Opinion on Drug Metabolism and Toxicology
JF - Expert Opinion on Drug Metabolism and Toxicology
IS - 7
ER -