Emerging new small molecules in peripheral t-cell lymphomas

Survival outcomes for patients with peripheral T-cell lymphomas (PTCLs) who relapse or progress after first-line treatment are very poor. Newer agents targeting specific molecular hallmarks of the disease entities are urgently needed and may represent a rational approach to improve the treatment for patients with relapsed and refractory PTCL. This chapter reviews the mechanisms of action and the potential clinical role of some of the more promising emerging new small molecules. The Janus-associated kinase-signal transducers and activators of transcription (JAK-STAT) pathway is commonly deregulated in PTCL and mutations in the JAK and STAT system in T-cell neoplasms have been detected in the SH2 domain of STAT3 and STAT5 and in the pseudokinase domain of JAK1 and JAK3. The phosphatidylinositol 3 kinases may represent an important class of drugs that require further study in the T-cell malignancies.