This signaling can in turn reactivate the PI3K/Akt/mTOR pathway [75], activate the Janus kinase 2 (JAK2)/signal transducer and activator of the transcription 5 (STAT5) pathway to promote cell proliferation and survival [76] or activate the oncogenic kinase MAPK4, which can activate the Akt/mTOR axis independently of PI3K, conferring resistance to PI3K inhibitors, particularly in BL subtypes where MAPK4 is often overexpressed [77]. The gene discussed is PIK3CA; the disease is Burkitt lymphoma.