Felix A Mensah, Jean-Pierre Blaize, Locke J Bryan

The importance of the phosphatidylinositol-3-kinase (PI3K) pathway in cell survival and proliferation has made it an attractive target in cancer therapy. The development of small molecule inhibitors for the PI3K pathway continues to provide treatment alternatives across a range of malignancy types. Several agents, including idelalisib, copanlisib and duvelisib, not only inhibit the PI3K pathway, but also have effects on associated mechanisms including the ATK and mTOR pathways. The advent of PI3K-specific small molecular inhibitors has led to increased efficacy with avoidance of an excessive toxicity profile. Key enzymes of the PI3K pathway exhibit differing expression in tissue types and roles in tumor pathogenesis. Copanlisib (BAY 80-6946) is a pan-specific PI3K small molecule inhibitor for four key isoforms with increased activity against PI3Kα and PI3Kδ, both important in B-cell malignancies. Follicular lymphoma is one of the most common indolent B-cell non-Hodgkin lymphomas worldwide. Follicular lymphoma like other indolent B-cell non-Hodgkin lymphomas is beleaguered by high relapse rates and the need for subsequent therapy options. Based on efficacy and a limited toxicity profile, copanlisib received accelerated US Food and Drug Administration approval for the treatment of adult patients with relapsed follicular lymphoma following two lines of therapy. Here, we review the development of copanlisib and the role of this agent in the treatment of follicular lymphoma.