Cell signaling modifiers for molecular targeted therapy in ATLL.

Adult T-cell leukemia/lymphoma (ATLL) is a malignancy of peripheral T lymphocytes caused by human T-cell leukemia virus type 1 (HTLV-1) infection. Available therapies for ATLL have minimal efficacy, with few responders and poor survival. New therapies are needed for ATLL patients. Three decades of research in this field has resulted in accumulation of a wealth of knowledge about the molecular pathways underlying the proliferation of HTLV-1-infected T cells. Inappropriate over- and under-activation of various signaling pathways can contribute to pathological processes such as neoplasia. Molecular and pharmacological interventions that target the aberrant state of activation are thus of potential therapeutic benefit. Here we review how signal transduction pathway components including nuclear factor-kappaB, activator protein-1, janus kinase-signal transducer and activator of transcription, and phosphatidylinositol 3-kinase-Akt contribute to the pathogenesis of ATLL. The targeted inhibition of such molecules to suppress the growth of HTLV-1-infected T cells both in vitro and in vivo is also discussed. The potential translation of such strategies into effective therapies for patients with ATLL may improve the poor outcome associated with this neoplasia.