RAF proto-oncogene, also known as c-Raf or even Raf-1, is an serine/threonine-protein kinase encoded by the RAF1 gene in humans. The c-Raf protein is a part of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) module (MAP3K) that functions downstream of the Ras subfamily of membrane associated GTPases. Both C-Raf (Raf-1) and B-Raf form heterodimers to yield higher MEK kinase activity for cell proliferation and tumor development in response to growth factor stimulation and Ras activation [Casar B, Pinto A]. Previous reports in squamous cell carcinoma and lung adenocarcinoma have shown that overexpression of Raf-1 was well correlated with metastatic progression [Hagemann C, Gloger J]. In addition, significant levels of tumor regression were observed with ablation of RAF1 in advanced lung adenocarcinomas induced by Kras and Trp53 mutations (Sanclemente et al., 2018). In combination with the EGF receptor, RAF1 ablation also resulted in complete regression of a subset of pancreatic ductal adenocarcinomas (Blasco et al., 2019). Inhibition of RAF1 kinase activity based on the current therapeutic strategies are unlikely to produce anti-tumor results in the clinic. Instead, pharmacological targeting of RAF1 either by blocking its interaction with the ASK1 or MST2 kinases (Chen et al., 2001; O’Neill et al.,2004) or by inhibiting RAF1 expression with selective RAF1 degraders prevent the anti-apoptotic activity of RAF1.