Editorial [Hot Topic:Strategies for Molecular-Based Treatment of Hematological Malignancies (Guest Editor: Per Ole Iversen)]

Although the hematological malignancies constitute a minor fraction of the total number of newly diagnosed cancers per year, they pose a substantial burden to the individual patient. In general neoplasias affecting the lymphohematopoietic system carry a poor prognosis with median 5- year survival rates usually below 50-60%, and some are still considered incurable, like chronic lymphoid leukemia and multiple myeloma. Today the best treatment modalities are often composed of a combination of intensive chemotherapy and stem cell transplantation. These therapeutic regimens are usually offered to the younger population of patients (< 60 years), the treatmentrelated side effects might be severe, and importantly, they are costly in terms of financial and personnel resources. Hence there is a continuous need to expand our knowledge of normal and malignant hematopoiesis in order to improve our treatment repertoire of these diseases. This issue of Current Drug Targets contains an update of recent advances in the development of molecular-based strategies for treating chronic diseases with special emphasis on cancers, in particular the hematological malignancies. In the growing era of proteomics, Sjoholt and colleagues describe how these new and fascinating techniques can be adapted to study leukemogenesis, how putative therapeutic targets can be identified, and they also add to our understanding of how current cytostatic drugs affect the leukemic cell. The possibility of selective silencing of genes involved in the development and dissemination of malignant cells, is the focus of the paper by Sioud and Iversen. The advent of small-molecular oligonucleotides to effectively impair gene expression is pawing their way into modern cancer treatment. Skalhegg and co-workers have a long standing interest in the biology of protein A kinases, and here they pinpoint potential targets for treating diseases characterized by dysfunctional T cells by interfering with the protein kinase A signaling pathways. The transition from a single malignant cell clone to spread of these cells to more distant sites, is still far from being adequately understood. In their review Fjelstad and Kolset focus on the extracellular compartment and how the inherent components operate and can be inhibited during the metastatic process. Angiogenesis is increasingly being accepted as an important mechanism for how blood cancers disseminate, and putative angiogenic targets for cancer therapy are outlined by Negaard et al. In addition to the invariable impairment of bone marrow hematopoiesis, patients with multiple myeloma frequently experience bone pains due to osteolytic destructions of their skeletons. Hjertner and colleagues describe the molecular mechanisms for such osteolytic destructions and define possible targets for therapy. The myelodysplastic syndromes have remained a major obstacle to clinicians, both in terms of ill-defined diagnostic criteria and the lack of adequate treatment. Hellstrøm-Lindberg presents an overview of how this group of hematolological malignancies can be categorized and how new molecular-based knowledge about the onset and development of these diseases can be exploited for design of more efficient treatment. Collectively, it is my hope that these reviews will aid in our understanding how molecular-based strategies can be implemented to identify putative targets for therapy and thus for translating basic science into applied clinical practice.