PI3Kδ is one of four PI3K isoforms that play key roles in cell growth, differentiation and survival. The PI3Kα and PI3Kβ isoforms are expressed in nearly all cell types and have been targeted in solid tumors, whereas the PI3Kγ and PI3Kδ isoforms are found primarily on immune cells. Several companies are developing inhibitors of PI3Kδ for hematological malignancies, autoimmune diseases and inflammatory indications in which the isoform is overactive. It is showed that the subtype to be important for the differentiation, expansion and normal function of T and B cells. when the researchers established tumors in mutant Pi3kd mice with cells from breast, lung and other solid tumors, they saw the mutant mice developed smaller primary tumors and fewer metastases and survived longer than wildtype mice given the same treatment. In addition, PI-3065—a PI3Kδ inhibitor from Roche's Genentech Inc. unit—decreased growth of breast and pancreatic tumors in wildtype mice and increased survival compared with vehicle.
Ali K, Soond D R, Pi?eiro R, et al. Corrigendum: Inactivation of PI (3) K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer[J]. Nature, 2016.