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Figure 10. An overview of the MAPK/ERK pathway and its role in overcoming cancer cell drug resistance by sesquiterpene lactones. The MAPK/ERK pathway is a critical signaling cascade involving three classes of kinases: MAPKKK, MAPKK, and MAPK, which sequentially phosphorylate downstream targets. It begins with the activation of MAPKKKs, which subsequently activate MEK1 and MEK2. These, in turn, lead to the activation of ERK1 and ERK2, the final effectors of the cascade. Alterations in components of the Ras/BRAF/MEK/ERK pathway can result in the sustained activation of downstream signaling. This continuous activation promotes the expression of genes involved in cell survival and proliferation, enhances anti-apoptotic signaling, and ultimately contributes to chemotherapy resistance. Furthermore, the MAPK/ERK pathway interacts with the TRAIL pathway, working together to regulate drug resistance. MAPK: Mitogen-activated protein kinase; ERK: extracellular signal-regulated kinase; MAPKKK: MAPK kinase kinase; MAPKK/MEK: MAPK kinase; TRAIL: tumor necrosis factor-related apoptosis-inducing ligand.