A 70-year-old woman with cough was diagnosed with pulmonary adenocarcinoma by bronchoscopic transbronchial biopsy. She was diagnosed cT2N0M0, stage IB clinically, and the tumor was surgically resected. Postoperative pathology was confirmed to be pleomorphic carcinoma of pT2N2M0, stage III A. She received 6 courses of adjuvant chemotherapy consisting of cisplatin and docetaxel. Five months later, new pulmonary and bone metastases were detected. Gefitinib was started, and she has shown stable disease for 7 months. Epidermal growth factor receptor (EGFR) mutation was observed in her tumor specimens.

There are two types of radiopharmaceuticals for cancer imaging with PET. The first target is a marker of cancer proliferation, and positron-labeled analogs of glucose, amino acid, and nucleic acid are commonly used for this purpose. 18F-FDG is a typical tracer of this approach. The second target is visualization of cancer-specific biological characters. In Tohoku University, we developed 18F-fluorodeoxygalactose(18F-FDGal), 18F-SAV03M, and 18F-FRP170 as tracers of the second category. 18F-FDGal is metabolized and trapped in the tissue by liver-specific galactose metabolic enzymes. It is used for detecting well-differentiated hepatocellular carcinoma which originated from liver cells and still maintains the enzymes. 18F-SAV03M is a substrate for matrix metalloproteinase-2 and was developed for the visualization of tumor invasiveness. 18F-FRP170 was developed for the visualization of hypoxic cancer cells which cause radiotherapy and chemotherapy resistance. In addition, the uses of labeled antisense oligonucleotide and aptamers were introduced for the visualization of specific mRNA and proteins expression.

Molecular markers have long been studied and used in part as a marker for prediction of prognosis and deciding the treatment for patients with breast cancer. Now development of novel decision-making biomarkers for adjuvant chemotherapy is desired for many patients with hormone receptor-positive early breast cancer. Thanks to recent advances in molecular marker studies on breast cancer, the update committee has systematically reviewed the literature and updated recommendations for the use of tumor markers in breast cancer, one of the ASCO clinical practice guidelines, in 2007. In the revised guideline, gene expression profiling assays are topics in six newly added categories. In this review, the key guideline recommendations and two innovative gene expression profiling assays have been summarized.

Fluoropyrimidine such as 5-fluorouracil(5-FU)exerts its antitumor activities via anabolism by several enzymes. Genetic polymorphisms of these enzymes related to sensitivity and toxicity of fluoropyrimidines are reviewed. Expression of thymidylate synthase(TS), a target enzyme of 5-FU, is regulated by variable number of a 28 bp tandem repeat in the enhancer region. The double tandem repeat is associated with low TS expression, and consequently, patients with double tandem repeat demonstrated higher sensitivity to 5-FU than those with triple tandem repeat. Single nucleotide polymorphism within the second tandem repeat and loss of heterozygosity are also reported to be related to fluoropyrimidine sensitivity. In addition, patients having a 6 bp deletion in 3'-UTR region showed remarkably high antitumor activity by 5-FU based chemotherapy. Genetic variations in 5-FU catabolic enzymes can also have a profound effect on 5-FU toxicity. So far 39 mutations/ polymorphisms have been identified in dihydropyrimidine dehydrogenase(DPD)gene, a major catabolic enzyme of 5- FU. Among them, IVS14+1G>A is reported to be highly associated with severe toxicity caused by chemotherapy with fluoropyrimidine. A polymorphism that may influence the efficacy of 5-FU by influencing folate pools is that of the methylenetetrahydrofolate reductase(MTHFR)gene. C677T mutation was associated with a higher response rate on 5-FU/folinic acid chemotherapy. Prospective clinical trials to confirm the predictability of genetic polymorphism for sensitivity and toxicity of 5-FU should be performed.

Oxaliplatin has been the main treatment of choice in colorectal cancer in advanced settings. However, cellular mechanisms for the uptake, intracellular distribution and efflux of oxaliplatin are unknown. GST(glutathione S transferase)is member of a superfamily of metabolic enzymes that play an important role in the cell defense system. Current data suggest that GST-pi is associated with increased resistance to platinum-based chemotherapy. Specific roles for the single nucleotide polymorphisms in GST-pi gene GSTP1 in the treatment with oxaliplatin based chemotherapy, have been demonstrated in recent years.

Vinca alkaloids inhibit microtubule formation by binding to tubulin. There are four clinically available vinca alkaloids including vincristine, vinblastine, vindesine, and vinorelbine. P-glycoprotein(P-gp)is the one of the efflux adenosine triphosphate(ATP)-binding cassette family transporters and is the encoded product of MDR1 gene. P-gp is overexpressed not only in tumor cells resistant to multiple anticancer agents but also found in normal cells such as liver, gastrointestinal tract and kidney, working as a biological defense mechanism. Single nucleotide polymorphisms for MDR1 in exon 12(1236), exon 21(2677), and exon 26(3435)have been well studied. Although C1236T and C3435T do not change the amino acid, G2677T and G2677A result in amino acid substitution of Ala893Ser and Ala893Thr, respectively. In the use of haplotypes to predict vincristine pharmacokinetics, the correlation between the haplotypes and the elimination half-life was reported. Many studies of the relationship between polymorphism/haplotype for MDR1 and pharmacodynamics including efficacy and toxicity of chemotherapy have been explored.

We summarized the relationship between EGFR gene polymorphisms/mutations and gefitinib(Iressa). The SNPs of CA-simple sequence repeat of EGFR intron 1 and promoter sequence were reported to be related to the sensitivity and/ or toxicity of gefitinib(Iressa). Many reports have shown that there are differences between gefitinib responders and non-responders in the frequency of activating mutations and/or amplification in the EGFR gene, which suggests that such mutations might be predictive markers for sensitivity to gefitinib. However, there are known to be gefitinib-sensitive and intermediate-sensitive tumors that have no activating mutations in the EGFR gene, including gene amplification. SNPs in EGFR gene may be one of candidates for predictors of sensitivity. On the other hand, the incidence of gefitinib-induced lung injury was 3.98% in Japan(case-control study, AstraZeneca), which is higher than the correspondence rate, 0.3%, in the USA(FDA Approval Letter). Further studies about the prediction of drug-induced interstitial lung disease including SNPs analyses of the EGFR gene and other related molecules.