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Open Access Highly Accessed Research article

Anticancer drug clustering in lung cancer based on gene expression profiles and sensitivity database

Akihiko Gemma1*, Cai Li1, Yuka Sugiyama1, Kuniko Matsuda1, Yoko Seike1, Seiji Kosaihira1, Yuji Minegishi1, Rintaro Noro1, Michiya Nara1, Masahiro Seike1, Akinobu Yoshimura1, Aki Shionoya2, Akiko Kawakami2, Naoki Ogawa2, Haruka Uesaka3 and Shoji Kudoh1

Author Affiliations

1 The Fourth Department of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113–8602, Japan

2 Genetic Lab Co., Ltd, 2–12, N27-W6, Kita-ku, Sapporo, Hokkaido, 001–0027, Japan

3 MediBic, Daido Kasumigaseki Bldg, 8F, 1-4-2 Kasumigaseki, Chiyoda-ku, Tokyo, 100–0013, Japan

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BMC Cancer 2006, 6:174  doi:10.1186/1471-2407-6-174

Published: 30 June 2006

Abstract

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.

Conclusion

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.