A Review of Phosphocreatine 3 Kinase δ Subtype (PI3Kδ) and Its Inhibitors in Malignancy

Most cancer deaths are caused by metastasis. The phosphocreatine 3-kinase (PI3K) family includes the I–III classes, with class I divided into 4 subtypes (α, β, γ, δ); and PI3K signaling participates in the regulatory processes of cell proliferation, differentiation, apoptosis, and glucose transport. Moreover, PI3Ks are modulators of cellular membrane lipids involved in signaling and trafficking events. The PI3Kdelta isoform (PI3Kδ), which is not only specifically expressed in hematopoietic cells, but also in different tumor cell lines, is expressed extensively. The increase in PI3Kδ activity is often associated with a variety of cancers. Currently, the strategy of tumor therapy based on PI3Kδ and its related signaling pathway is developing. Besides its established role in controlling functions in autoimmunity and inflammation, the role of PI3Kδ in tumor and metastasis is not clearly elucidated, with the effects of inhibiting PI3Kδ in several types of tumors also remaining unexplored. In addition, the specific inhibitor of PI3Kδ in tumor progression and metastasis and its underlying mechanism need to be further studied. The purpose of this review is to rationalize the existing functions and mechanisms of PI3Kδ in tumor metastasis and the relationship with hematopoietic cells in cancers as well cross-talking with miRNA, which provides a new theoretical basis and potential therapeutic target for the drug therapy of tumor metastasis.