A literature review of molecular markers predictive of clinical response to cytotoxic chemotherapy in patients with lung cancer.
BACKGROUND
To find candidate genes for a predictive chemosensitivity test in patients with lung cancer by using a literature review.


METHODS
Using MEDLINE searches, "in vitro chemosensitivity associated genes" and articles on association of the gene alteration with clinical chemosensitivity in lung cancer patients were selected. We calculated odds ratios (ORs) and their 95% confidence intervals (95% CIs) of response rates for patients who had tumors with or without gene alteration. Combined ORs and 95% CIs were estimated using the DerSimonian-Laird method.


RESULTS
Of the 80 in vitro chemosensitivity-associated genes identified, 13 genes were evaluated for association with clinical chemosensitivity in 27 studies. The median (range) number of patients in each study was 50 (range, 28-108). The response rates of lung cancer with high and low P-glycoprotein expression were 0% and 73% to 85%, respectively (p < 0.001). Glutathione S-transferase pi expression (OR 0.22, 95% CI 0.06-0.79), excision repair cross-complementing 1 alterations (combined OR 0.53, 95% CI 0.28-1.01; p = 0.055), and tumor suppressor p53 mutation (combined OR 0.25, 95% CI 0.12-0.52) were associated with clinical chemosensitivity.


CONCLUSIONS
In total, 80 in vitro chemosensitivity-associated genes were identified in the literature, and high and low P-glycoprotein, glutathione S-transferase pi expression, excision repair cross-complementing 1 alterations, and tumor suppressor p53 mutation were candidates for future clinical trials of chemosensitivity tests in lung cancer patients.
Sekine
Ikuo
I
Divisions of Thoracic Oncology and Internal Medicine, National Cancer Center Hospital, Tokyo, Japan.
Minna
John D
JD
Nishio
Kazuto
K
Tamura
Tomohide
T
Saijo
Nagahiro
N
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D003603:Cytotoxins / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D051549:Glutathione S-Transferase pi / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D003603:Cytotoxins; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D051549:Glutathione S-Transferase pi