We report a sixteen-year-old boy with Down syndrome and relapse of AML (M7), who has been in complete remission (CR) more than 12 months after bone marrow transplantation (BMT) from an HLA-matched sibling donor. Because monosomy 7 was detected at onset of AML and he experienced relapse after the treatment of AML 99 Down protocol, his prognosis was considered very poor. However, he achieved CR following chemotherapy that included high-dose AraC and BMT from an HLA-matched sibling donor without severe complication. He has remained in CR for more than 12 months after BMT. In this case, GATA1 mutation was not detected at either onset or relapse of AML and it is suggested that this case is in a different risk group than the usual Down syndrome patient with AML showing GATA1 mutation.

Over the past decade, molecular-targeted therapies have been added to cytotoxic and anti-endocrine drugs in the treatment of cancer, with an aim to target the molecular pathways underlying the carcinogenic processes and maintaining cancer phenotypes. Success with some of these agents has suggested that identification and validation of the drug target is the starting point to the route of development of active, safe, and effective drugs. The main molecular targets employed for the development of anticancer drugs are cell surface receptors, signal transduction pathways, gene transcription targets, ubiquitin-proteasome/heat shock proteins, and tumor microenvironment components (especially, antiangiogenic agents). In this paper, we review the development of the main molecular targeted non-cytotoxic agents investigated in glioma, highlighting lessons derived from the development of these novel drugs and proposing new horizons for the clinical development of molecular-targeted therapies.

Although imatinib mesylate therapy is effective for chronic myeloid leukemia (CML) patients, there are still some unanswered questions. It is unclear whether imatinib can actually cure CML and whether this therapy can be safely discontinued in patients showing complete cytogenetic and molecular responses. This report describes the clinical outcome of a patient with chronic phase CML who discontinued imatinib therapy after achieving molecular remission. This patient has shown a relapse based on transcription-mediated amplification-hybridization protection assay (TMA-HPA) to monitor BCR-ABL transcripts, highlighting the uncertainty of discontinuing imatinib therapy for five months.

A 68-year-old female complained of anemia and bone pain. Monoclonal increase of plasma IgA, lambda-type was observed, and immature plasma cells were detected in the bone marrow. These plasma cells showed intermediate differentiation on CD38 gating flow cytometry. Chromosomal analysis demonstrated complex abnormalities including repeats and translocation, t(8;22)(q24;q11.2) by G-banding, and breakpoint down stream of 3'c-MYC on fluorescence in situ hybridization. Multiple myeloma with variant type translocation was diagnosed. Treatment with continuous infusion of dexamethasone and oral administration of thalidomide effectively decreased IgA, plasma cells and chromosomal abnormality, facilitating complete remission.

The histology of esophageal cancer represents squamous cell carcinoma mainly in Eastern countries and adenocarcinoma in Western countries. This difference entails differences in treatment strategy. Thus, clinical studies in Japan are necessary, although recent trials showed marvelous progress. By adopting pharmacogenetic approaches for not only biomarkers but also targeting therapies, surgery can be surpassed in the near future.

The correlations between mRNA expressions of 5-fluorouracil(5-FU)-related enzymes; thymidylate synthase(TS), dihydropyrimidine dehydrogenase(DPD), thymidine phosphorylase(TP), and orotate phosphoribosyltransferase (OPRT)in breast cancers, along with disease-free survival(DFS), were investigated in 35 patients treated with postoperative adjuvant chemotherapy using cyclophosphamide, methotrexate and 5-fluorouracil(CMF). The patients treated with CMF were divided into two groups, a lower group(L group)and a higher group(H group), according to the median value of the mRNA expression for each enzyme in 220 breast cancer specimens, which were resected between 1996 and 1998 in our institute. 5-year DFS was not significantly different between TS-L and H group(60% and 80%, p=0.38), DPD-L and H group(57.9% and 86.7%, p=0.088), and TP-L and H group(70% and 73.3%, p=0.89), respectively. 5-year DFS in the OPRT-H group(88.9%)was significantly better than that in the OPRT-L group(50%) (p=0.024). In the OPRT-H group, despite the fact that the proportion of patients with lymph node involvement in the CMF group was significantly higher than that in the postoperative adjuvant hormone therapy group, 5-year DFS was not significantly different between the two groups(p=0.10). Our results suggest that OPRT level was the significant predictive marker for DFS in the breast cancer patients treated with postoperative adjuvant chemotherapy using CMF.

Biomarkers for lung cancer may be used for early detection, diagnosis, treatment selection and prognostication. They are also expected to contribute to the realization of tailored therapy. To identify the optimal therapy candidates, EGFR (epidermal growth factor receptor)mutations are biomarkers available as predictive factors for EGFR tyrosine kinase inhibitors and UGT(uridine diphosphate glucuronosyltransferase)1A1 as a risk predictor of irinotecan in the present practice. Novel potential biomarkers for prognostication have been developed by genomic methods. Biomarker development for early detection is much awaited for the future.

Biomarkers play important roles in breast cancer management, i. e. diagnosis, treatment selection, and therapeutic monitoring. While the basic treatment strategy depends on the status of hormone receptors and HER2, other molecules are intensively studied for biomarkers to predict treatment efficacies. Gene expression profiles have been developed to predict prognosis and treatment efficacies. Circulating tumor cells and endothelial cells are drawing attention for therapeutic monitoring. It is essential to understand biomarkers for the progress of personalized medicine.