Editorial [Hot Topic: Innovative Therapeutical Approaches for Hematological Malignancies Based on Molecular Targeted Therapies (Executive Editor: Giorgio Zauli) ]

This special issue of Current Pharmaceutical Design is focussed on innovative therapeutical approaches for hematological malignancies based on molecular targeted therapies. Macor group [1] summarizes recent advances in human tumor xenograft models for moving toward more clinically relevant models, which are essential for characterizing potential therapeutic targets in cancer therapy, including hematological malignancies. Calin group [2] describes the potential involvement of microRNAs in the regulation of neoplastic hematopoiesis and provides background on the biogenesis and function of miRNAs, discussing the potential therapeutic applications of miRNA-based technology in hematological malignancies. Phipps' group [3] shows the link between the overexpression of a key modulator of inflammation, such as cyclooxygenase-2 (Cox-2), and the ability of some hematological malignancies to avoid immune responses by producing factors that enhance angiogenesis and the metastastatic potential. Thus, Cox-2 selective inhibitors, which are already used in clinical practice, have promising therapeutic also for the treatment of hematological malignancies. The reviews of van Blitterswijk [4] and Vaccarezza [5] groups outline the importance of key intracellular pathways, such as Akt and PKC in the development of hematological malignancies and the new therapeutic opportunities provided by synthetic anticancer alkylphospholipids (APLs), such as perifosine and enzastaurin, which act on cellular membranes rather than at the DNA level. Di Pietro [6] provides an overview on the use of fully humanized agonistic monoclonal antibodies targeting TRAIL-death receptors in clinical trials including hematological malignancies. Such approach is particularly promising, expecially if associated to anti-CD20 rituximab antibody, in B cell malignancies. Finally, starting from the observation that most hematological malignancies display a wild-type p53 status, Secchiero et al. [7] describes the potential use of small molecule inhibitors of the p53/MDM-2 interactions, able to activate or re-activate the p53 pathway in primary malignant cells. References [1] Macor P, Secco E, Zorzet S, Tripodo C, Celeghini C, Tedesco F. An Update on the Xenograft and Mouse Models Suitable for Investigating New Therapeutic Compounds for the Treatment of B-Cell Malignancies. Curr Pharm Des 2008; 14(21): 2023-2039. [2] Barbarotto E, Calin GA. Potential Therapeutic Applications of miRNA-Based Technology in Hematological Malignancies. Curr Pharm Des 2008; 14(21): 2040-2050. [3] Bernard MP, Bancos S, Sime PJ, Phipps RP. Targeting Cyclooxygenase-2 in Hematological Malignancies: Rationale and Promise. Curr Pharm Des 2008; 14(21): 2051-2060. [4] van Blitterswijk WJ, Verheij M. Anticancer Alkylphospholipids: Mechanisms of Action, Cellular Sensitivity and Resistance, and Clinical Prospects. Curr Pharm Des 2008; 14(21): 2061-2074. [5] Mischiati C, Melloni E, Corallini F, Milani D, Bergamini C, Vaccarezza M. Potential Role of PKC Inhibitors in the Treatment of Hematological Malignancies. Curr Pharm Des 2008; 14(21): 2075-2084. [6] Sancilio S, Grill V, Di Pietro R. A Combined Approach with Rituximab Plus Anti-TRAIL-R Agonistic Antibodies for the Treatment of Haematological Malignancies. Curr Pharm Des 2008; 14(21): 2085-2099. [7] Secchiero P, di Iasio MG, Gonelli A, Zauli G. The MDM2 Inhibitor Nutlins as an Innovative Therapeutic Tool for the Treatment of Hematological Malignancies. Curr Pharm Des 2008; 14(21): 2100-2110.