Anticancer drug clustering in lung cancer based on gene expression profiles and sensitivity database.
BACKGROUND
The effect of current therapies in improving the survival of lung cancer patients remains far from satisfactory. It is consequently desirable to find more appropriate therapeutic opportunities based on informed insights. A molecular pharmacological analysis was undertaken to design an improved chemotherapeutic strategy for advanced lung cancer.


METHODS
We related the cytotoxic activity of each of commonly used anti-cancer agents (docetaxel, paclitaxel, gemcitabine, vinorelbine, 5-FU, SN38, cisplatin (CDDP), and carboplatin (CBDCA)) to corresponding expression pattern in each of the cell lines using a modified NCI program.


RESULTS
We performed gene expression analysis in lung cancer cell lines using cDNA filter and high-density oligonucleotide arrays. We also examined the sensitivity of these cell lines to these drugs via MTT assay. To obtain our reproducible gene-drug sensitivity correlation data, we separately analyzed two sets of lung cancer cell lines, namely 10 and 19. In our gene-drug correlation analyses, gemcitabine consistently belonged to an isolated cluster in a reproducible fashion. On the other hand, docetaxel, paclitaxel, 5-FU, SN-38, CBDCA and CDDP were gathered together into one large cluster.


CONCLUSIONS
These results suggest that chemotherapy regimens including gemcitabine should be evaluated in second-line chemotherapy in cases where the first-line chemotherapy did not include this drug. Gene expression-drug sensitivity correlations, as provided by the NCI program, may yield improved therapeutic options for treatment of specific tumor types.
Gemma
Akihiko
A
The Fourth Department of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan. agemma@nms.ac.jp
Li
Cai
C
Sugiyama
Yuka
Y
Matsuda
Kuniko
K
Seike
Yoko
Y
Kosaihira
Seiji
S
Minegishi
Yuji
Y
Noro
Rintaro
R
Nara
Michiya
M
Seike
Masahiro
M
Yoshimura
Akinobu
A
Shionoya
Aki
A
Kawakami
Akiko
A
Ogawa
Naoki
N
Uesaka
Haruka
H
Kudoh
Shoji
S
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D016208:Databases, Factual; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor / Q000706:statistics & numerical data; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003841:Deoxycytidine; D000093542:Gemcitabine