The article reviews the RAS-RAF-MEK-ERK (RAS-MAPK) signaling pathway's role in cancer and its potential as a therapeutic target. The RAS-MAPK pathway is crucial for cell growth, differentiation, and survival, and its dysregulation is frequently observed in human cancers. Activating mutations in RAS and BRAF genes are common in various cancers, making these pathways attractive for targeted therapy. Small-molecule inhibitors targeting this pathway are currently under clinical trials. The RAS-MAPK pathway is activated by growth factors and cytokines through receptor tyrosine kinase signals and by activating mutations in RAS and RAF genes. The pathway involves several key components, including RAS, RAF, MEK, and ERK, which transmit signals from the cell surface to the nucleus, regulating gene expression and cellular functions. RAS mutations are prevalent in cancers such as pancreatic, colorectal, and lung cancers, while BRAF mutations are common in melanoma and thyroid cancers. MEK inhibitors, such as PD 0325901 and AZD6244, have shown promise in clinical trials, with some demonstrating antitumor activity and manageable side effects. However, their efficacy is limited by factors such as tumor heterogeneity and compensatory pathways. RAF inhibitors, including PLX4032 and GSK2118436, have also shown clinical activity, particularly in BRAFV600E-mutated cancers. However, resistance mechanisms, such as the activation of alternative pathways, can limit their effectiveness. The article emphasizes the need for combination therapies to overcome resistance and improve outcomes. It highlights the importance of identifying biomarkers for patient selection and the potential of combining different inhibitors (e.g., RAS, RAF, MEK, and PI3K inhibitors) to target multiple pathways. Future research should focus on understanding the complex interactions within the RAS-MAPK pathway and developing more effective, personalized treatment strategies.The article reviews the RAS-RAF-MEK-ERK (RAS-MAPK) signaling pathway's role in cancer and its potential as a therapeutic target. The RAS-MAPK pathway is crucial for cell growth, differentiation, and survival, and its dysregulation is frequently observed in human cancers. Activating mutations in RAS and BRAF genes are common in various cancers, making these pathways attractive for targeted therapy. Small-molecule inhibitors targeting this pathway are currently under clinical trials. The RAS-MAPK pathway is activated by growth factors and cytokines through receptor tyrosine kinase signals and by activating mutations in RAS and RAF genes. The pathway involves several key components, including RAS, RAF, MEK, and ERK, which transmit signals from the cell surface to the nucleus, regulating gene expression and cellular functions. RAS mutations are prevalent in cancers such as pancreatic, colorectal, and lung cancers, while BRAF mutations are common in melanoma and thyroid cancers. MEK inhibitors, such as PD 0325901 and AZD6244, have shown promise in clinical trials, with some demonstrating antitumor activity and manageable side effects. However, their efficacy is limited by factors such as tumor heterogeneity and compensatory pathways. RAF inhibitors, including PLX4032 and GSK2118436, have also shown clinical activity, particularly in BRAFV600E-mutated cancers. However, resistance mechanisms, such as the activation of alternative pathways, can limit their effectiveness. The article emphasizes the need for combination therapies to overcome resistance and improve outcomes. It highlights the importance of identifying biomarkers for patient selection and the potential of combining different inhibitors (e.g., RAS, RAF, MEK, and PI3K inhibitors) to target multiple pathways. Future research should focus on understanding the complex interactions within the RAS-MAPK pathway and developing more effective, personalized treatment strategies.