Corrigendum to “Reengineered tricyclic anti-cancer agents” [Bioorg. Med. Chem. 23 (2015) 6528–6534]

Direct activation of PP2A for the treatment of tyrosine kinase inhibitor–resistant lung adenocarcinoma

“…PP2A activation by SMAPs simultaneously inhibits MAPK and PI3K oncogenic signaling pathways, which are downstream targets of the phosphatase, and their dephosphorylation seems to be regulated by the cellular abundance of target proteins ERK and AKT. We have shown in our recently published work that direct therapeutic activation of a phosphatase, such as PP2A, is a potentially novel strategy that aims to concurrently target several oncogenes with a single agent (16)(17)(18). Indeed, we have found that SMAPs directly bind to and activate PP2A in KRAS-mutant LUAD, therefore inhibiting tumor growth and inducing apoptosis in mouse xenografts, PDX models, and the transgenic KRAS LA2 murine model (17).…”

“…Our lab has successfully developed a published series of first-in-class small molecule activators of PP2A (SMAPs), which directly bind to PP2A and induce apoptosis and tumor growth inhibition in both transgenic and xenograft KRAS-driven mice models (16)(17)(18). SMAPs have been generated by repurposing and reengineering FDA-approved tricyclic neuroleptics through replacing the basic amine with a neutral polar functional group (19).…”