PIK3C2A and neoplasm: Together, the occurrence of BRAF and PIK3C2A mutations in the osimertinib-resistant xenograft tumor and the findings of Ichihara et al. [50] suggest that under continuous EGFR-TKI treatment, MAPK signaling independently contributes to tumor cell proliferation and survival through a mechanism downstream of EGFR, which overrides the effect of EGFR-TKI treatment.