Molecular-targeted therapy is to treat pathologic pathways specifically in tumor cell or tumor microenvironment. Specific molecular-targeted therapeutic agents for hormone-refractory prostate cancer (HRPC) include endothelin-A receptor antagonist, EGF receptor (EGFR) inhibitor, platelet derived growth factor receptor (PDGFR) inhibitor, nuclear factor of kappaB (NF-kappaB) inhibitor, cyclooxygenase-2 (COX2) inhibitor, and active form of Vitamin D. These agents have been investigated in clinical trials. So far, none of the above-mentioned agent has shown a sufficient clinical efficacy alone. However, docetaxel-based combinations with thalidomide or calcitriol have promising clinical activities. Further investigations are needed to optimize the molecular-targeted agents in the combinations with chemotherapeutic agents for the treatment of HRPC.

In this paper, we report on invasive urinary bladder carcinomas as follows, (1) p53 mutations have an important role in promotion and progression stages of carcinogenesis, (2) invasive bladder carcinomas occur multi-centrically in the bladder, (3) an organic arsenic, dimethylarsinic acid exerts carcinogenicity in the bladder of rats, (4) p53 mutations in carcinomas are caused by different carcinogens, and (5) bladder urothelium of people living in 137Cs-contaminated areas of Ukraine showed chronic proliferative atypical cystitis (so-called Chernobyl cystitis).

In the therapy of chronic myelogenous leukemia (CML), interferon (IFN) brought about a big progress resulting in the good hematologic as well as cytogenetic response and prolongation of survival. Recently, imatinib, the BCR/ABL antagonist, took over the first choice drug of the treatment CML. However, IFN still has the possibility to contribute the improvement of the therapy efficacy of CML.

The maintenance of genomic stability is an essential cellular function for a variety of well-coordinated regulation of biological activities of organisms, and a failure in its function results in the accumulation of mutations and/or abnormality in the induction of apoptosis, eventually leading to onsets of various diseases, including malignant tumors. DNA damage responses, in particular cell-cycle checkpoint regulation, play important roles in maintaining genomic integrity. In response to DNA damages induced by gamma-irradiation, ultraviolet irradiation, various chemicals, or reactive oxygen species (ROS), intrinsic cell-cycle checkpoint machinery is rapidly activated to arrest cells at particular cell-cycle points, and during cell-cycle checkpoint arrest cells may try to repair damaged DNAs, and then re-start cell-cycle upon the completion of DNA repair. Alternatively, if the extents of DNA damage overwhelm the capacity of the cellular repair machinery, cells may undergo apoptosis to prevent the accumulation of mutations within the organisms. In this article, we will first explain about our current view of DNA damage responses, in particular cell-cycle checkpoint regulation, and summarize our knowledge of the relationships between abnormalities of genes involved in DNA damage responses and malignant tumors, including hematopoietic malignancies. We will also discuss a possible implication of DNA damage responses in autoimmune diseases, such as rheumatoid arthritis.