臨床検査54巻10号

2010年10月発行

今月の主題 ファーマコゲノミクス 各論

抗癌剤と分子標的薬のファーマコゲノミクス

著者： 赤松弘朗¹ 山本信之¹

所属機関： ¹静岡県立静岡がんセンター呼吸器内科

ページ範囲：P.1138 - P.1142

　化学療法における効果・毒性プロファイルの一部は特定の遺伝子多型や変異・欠失といったゲノムバイオマーカーによって説明可能となってきた．1つは主に副作用の予測に用いられる患者自身の生殖細胞変異であり，もう1つは主に治療効果予測に用いられる癌細胞に生じた変異(体細胞変異)である．分子標的治療薬の開発においては後者に重点が置かれているが，CYP遺伝子多型などの生殖細胞変異に基づいたPK解析なども今後考慮していく必要がある．

参考文献

1) Sekine I, Yamamoto N, Nishio K, et al:Emerging ethnic differences in lung cancer therapy. Br J of Cancer　99：1757-1762，2008

2) Ma BB, Hui EP, Mok TS:Population-based differences in treatment outcome following anticancer drug therapies. Lancet Oncol　11：75-84，2010

3) Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group:Recommendations from the EGAPP Working Group:can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? Genet Med　11：15-20，2009

28 genotype and irinotecan-induced neutropenia:dose matters. JNCI　99：1290-1295，2007

5) Han JY, Lim HS, Shin ES, et al:Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin. J Clin Oncol　24：2237-2244，2006

6) Gandara DR, Kawaguchi T, Crowley J, et al:Japanese-US common-arm analysis of paclitaxel plus carboplatin in advanced non-small-cell lung cancer:a model for assessing population-related pharmacogenomics. J Clin Oncol　27：3540-3546，2009

7) Leskela S, Jara C, Leandro-Garca LJ, et al:Polymorphisms in cytochromes P450 2c8 and 3A5 are associated with paclitaxel neurotoxicity. Pharmacogenomics J 2010 ［Epub］

8) Myrand SP, Sekiguchi K, Man MZ, et al:Pharmacokinetics/genotype associations for major cytochrome P450 enzymes in native and first- and third-generation Japanese populations:comparison with Korean, Chinese, and Caucasian populations. Clin Pharmacol Ther　84：347-361，2008

9) Lynch TJ, Bell DW, Sordella R, et al:Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med　350：2129-2139，2004

10) Kobayashi K, Inoue A, Maemondo M, et al:First-line gefitinib versus first-line chemotherapy by carboplatin (CBDCA) plus paclitaxel (TXL) in non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutations:A phase III study (002) by North East Japan Gefitinib Study Group. ESMO2009, abstr 9LBA

11) Mitsudomi T, Morita S, Yatabe Y, et al:Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405):an open label, randomised phase 3 trial. Lancet Oncol　11：121-128，2010

12) Soda M, Choi YL, Enomoto M, et al:Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature　448：561-566，2007

13) Solomon B, Varella-Garcia M, Camidge DR, et al:ALK Gene Rearrangements. A new therapeutic target in a molecularly defined subset of non-small cell lung cancer. J Thorac Oncol　4：1450-1454，2009

14) Bang Y, Kwak EL, Shaw AT, et al:Clinical activity of the oral ALK inhibitor, PF-02341066, in ALK-positive patients with non-small cell lung cancer (NSCLC). J Clin Oncol 28 (supplu;uabstr 3)：18s，2010

15) http://www.nytimes.com/2010/06/06/health/research/06cancer.html?ref＝science

16) McDermott U, Settleman J:Personalized cancer therapy with selective kinase inhibitors:an emerging paradigm in medical. JCO　27：5650-5659，2009

17) Cusatis G, Gregorc V, Li J, et al:Pharmacogenetics of ABCG2and Adverse Reactions to Gefitinib. J Natl Cancer Inst　98：1739-1742，2006