SPRY4 and non-small cell lung carcinoma: In the AXL high expressing EGFR mutated NSCLC cells, SPRY4 protein, a negative regulator of MAPK pathway, inhibits activation of AXL, while suppression of MAPK pathway by osimertinib adversely activates AXL by inhibiting expression of AXL, resulting in emergence of tolerant cells by restoring MAPK signaling.3, 4