Phosphatidyl-inositol 3-kinase inhibitors in the treatment of T-cell lymphomas

Alessandro Broccoli, Pier Luigi Zinzani


A significant proportion of patients with T-cell lymphoma relapse after induction or are refractory to treatments. Therefore, there is an urgent need to develop new drugs with innovative mechanisms of action and limited toxicity pro les. Given that phosphatidyl-inositol 3-kinases (mainly δ and γ isoforms) play a pivotal role in regulating the malignant T-cell growth, proliferation and survival through the phosphorylation of their common effector Akt/PKB, their inhibition is supposed to allow the control of the disease in T-cell lymphoma patients who relapse or show refractoriness to conventional treatment or to other labeled drugs. Duvelisib, copanlisib and RP6530 have shown promising results in this context, and their role is reviewed.