Editorial [Hot Topic: New Perspectives in the Treatment of Hematological Malignancies (Guest Editor: Masahiro Kizaki)]

Significant advances in the molecular biology and therapy of hematological malignancies have been made over the last decade. The therapeutic approaches to the hematological malignancies such as acute and chronic leukemias, multiple myeloma, and malignant lymphoma are basically chemotherapy to eradicate the malignant cells. However, severe side effects and complications due to anti-cancer drugs are major problems in the clinical settings. Moreover, relapsed cases are usually refractory to chemotherapy and have poor prognosis. These clinical problems suggest that the current therapeutic strategies for the hematological malignancies have limitations and novel effective therapeutic approaches with less toxicity are needed. In the 1980s, the use of all-trans retinoic acid (ATRA) for differentiation-inducing therapy in acute promyelocytic leukemia (APL) has altered the therapeutic strategies of leukemia and dramatically improved the outcome. In addition, high remission rates in patients with chronic myeloid leukemia (CML) who receive imatinib mesylate indicate that molecular-targeted therapy for hematological malignancies is effective and safe. At the same time, progress in cellular biology has resulted in an increased understanding of the molecular genetics of the diseases and a characterization of the molecular targets for drug development. However, as for the other molecular-targeted agents, it is difficult to find a great deal of differences in the clinical outcome of patients who received standard therapies over the last decades. Therefore, investigators have actively sought out new agents with the ability to stimulate cellular differentiation and induce apoptosis in various cancer cells. Cellular proliferation, differentiation, and apoptosis are regulated by a number of extra- and intracellular molecules. These molecules mediate gene transcription either directly or indirectly by activating various signaling pathways. Molecular lesions of genes encoding for transcriptional factors are common oncogenic events in hematological malignancies. The complexicity of the transcriptional process offers a large number of substrates for designing therapeutic agents. However, the success of ATRA in the treatment of APL indicates that the targeted therapy for transcriptional factors can be highly effective and safe. As a consequence, the advances of molecular basis in hematological malignancies have spawned the development of effective agents such as monoclonal antibodies, specific enzyme inhibitors, and inhibitors of transcriptional factors. This special issue attempts to provide a practical introduction to the attractive and developing field of molecular-targeted therapy in hematological malignancies.