Hematologic Malignancies: An Opportunity for Targeted Drug Therapy

The Oncologist 2001;6(suppl 5):1-3 www.TheOncologist.com Correspondence: Janice L. Gabrilove, M.D., Chief, Division of Medical Oncology, Department of Medicine, Deputy Director for Clinical Affairs, The Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, USA. Telephone: 212-241-9650; Fax: 212-289-0678; e-mail: janice.gabrilove@mssm.edu Received September 14, 2001; accepted for publication September 19, 2001. ©AlphaMed Press 1083-7159/2001/$5.00/0 Molecular and cellular analyses over the last two decades have demonstrated unregulated growth, maturation, and cell survival as basic characteristics of many types of cancers [1]. Hematologic malignancies are among the most studied and well understood of all cancers. Common influences driving cell proliferation and survival in many of these diseases are growth factors. The aberrant production or overproduction of growth factors and chronic activation of their receptors are characteristic of many malignancies. Autocrine stimulation of malignant cells involves secretion of growth factors by the malignant cell itself, whereas paracrine stimulation occurs when the malignant cell depends on externally derived growth factors [2]. Regardless of their sources, these growth factors activate signal transduction pathways within the cell by binding to specific cell surface receptors and activating enzymatic functions. Many of the receptors are tyrosine kinases or are associated with kinase activity. Other enzymatic functions associated with signal transduction pathways include serine/threonine kinase activity, phosphatase, and GTPase activity [3]. The specific functions that are altered by growth factors in malignant cells ultimately lead to changes in gene expression and cell survival. Hematologic cancers are characterized by aberrant gene expression often resulting from specific genetic translocations or mutations that lead to unregulated signal transduction [4]. These types of alterations allow classification of leukemias and lymphomas into specific subgroups and frequently suggest treatment strategies. Unfortunately, currently available treatment options are generally associated with pronounced cytotoxicity, leading to the pancytopenia that is responsible for significant morbidity during and following treatment [5]. Together, the recent findings regarding specific biochemical pathways to malignancies and the toxicities of current therapies have spurred a search for new agents targeted to interfere with the particular aberrations found in cancer cells. The promise of such targeted agents is a tumor-selective action that will enhance activity while reducing treatment toxicities and promoting hematopoietic reconstitution.