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Possible model showing the cooperation of the activating mutations KRAS G12A and BRAF V600E in the present case of lung squamous cell carcinoma (LSCC). Simultaneous activation of the MEK/ERK signaling pathway by CRAF and BRAF occurs individually. BRAF V600E can transphosphorylate and hyperactivate CRAF in the presence of oncogenic KRAS, thus strongly augmenting MEK/ERK signaling activation. ERK-mediated negative feedback is highly resisted by BRAF-V600E.
