Targeting PP2A in cancer: Combination therapies

The serine/threonine phosphatase PP2A regulates a vast portion of the phosphoproteome including pathways involved in apoptosis, proliferation and DNA damage response and PP2A inactivation is a vital step in malignant transformation. Many groups have explored the therapeutic venue of combining PP2A reactivation with kinase inhibition to counteract the very changes in tumor suppressors and oncogenes that lead to cancer development. Conversely, inhibition of PP2A to complement chemotherapy and radiation-induced cancer cell death is also an area of active investigation. Here we review the studies that utilize PP2A targeted agents as combination therapy in cancer. A potential role for PP2A in tumor immunity is also highlighted. •PP2A is a tumor suppressor that negatively regulates numerous proliferative and survival pathways.•PP2A reactivation in combination with oncogenic kinase inhibition harbors therapeutic potential.•PP2A inhibition has also been shown to have tumoricidal effects, particularly when combined with DNA damaging agents.