Discovery of selective phosphatidylinositol 3-kinase inhibitors to treat hematological malignancies

The phosphatidylinositol 3-kinase (PI3K) signaling pathway is associated with chemoresistance and poor prognosis of many cancers, including hematological malignancies (HM), such as leukemia, lymphomas, and multiple myeloma (MM). Targeting PI3K is emerging as a promising strategy in the treatment of these blood cancers. Recent approval of idelalisib, a specific inhibitor of PI3Kδ, for the treatment of several types of HM, is likely to attract more interest in search for novel PI3K inhibitors. Here, we discuss classic and cutting-edge techniques and strategies to identify PI3K inhibitors for the treatment of HM. Each technique has its own strengths and limitations, and their combined application will accelerate the drug discovery process with fewer associated costs.