Emerging Therapeutic Landscape of Peripheral T-Cell Lymphomas Based on Advances in Biology: Current Status and Future Directions

Abstract

T-cell lymphomas are a relatively rare group of malignancies with a diverse range of pathologic features and clinical behaviors. Recent molecular studies have revealed a wide array of different mechanisms that drive the development of these malignancies and may be associated with resistance to therapies. Although widely accepted chemotherapeutic agents and combinations, including stem cell transplantation, obtain responses as initial therapy for these diseases, most patients will develop a relapse, and the median survival is only 5 years. Most patients with relapsed disease succumb within 2 to 3 years. Since 2006, the USFDA has approved five medications for treatment of these diseases, and only anti-CD30-therapy has made a change in these statistics. Clearly, newer agents are needed for treatment of these disorders, and investigators have proposed studies that evaluate agents that target these malignancies and the microenvironment depending upon the molecular mechanisms thought to underlie their pathogenesis. In this review, we discuss the currently known molecular mechanisms driving the development and persistence of these cancers and discuss novel targets for therapy of these diseases and agents that may improve outcomes for these patients.

Keywords: PTCL; current treatment; non-Hodgkin’s lymphoma; novel therapies; recent advances; targeted therapies.

Figure 1

Mechanisms of peripheral T-cell lymphoma development and agents used for targeted therapies. Multiple mechanisms are responsible for the development and proliferation of different subtypes of PTCL, including signaling pathway deregulation, epigenetic dysregulation, tumor microenvironment signals, and virus-mediated oncogenesis. Not all of these mechanisms are involved in the pathogenesis of each PTCL subtype. Some potential therapeutic targets and agents targeting them are also shown.