The article discusses the impact of complex apoptotic signaling pathways on cancer cell sensitivity to therapy. It summarizes current knowledge of signaling pathways involved in anticancer drug-induced cell death, including common apoptotic and antiapoptotic pathways, non-apoptotic cell death mechanisms (autophagy, necrosis), and signaling pathways in drug-sensitive and -resistant tumor cells. The review emphasizes the role of c-Jun/activator protein 1 (AP-1) and crosstalk with mitochondrial and endoplasmic reticulum (ER) pathways. It also discusses therapeutic implications of modifying signaling pathways leading to cell death, such as targeting cell death-related genes, interactions of drug resistance factors, and the unfolded protein response (UPR) pathway. The review highlights the importance of restoring altered signaling pathways to potentially restore drug sensitivity in tumor cells. The article covers the intrinsic and extrinsic apoptotic pathways, the role of JNK in apoptosis, the antiapoptotic pathway, and non-apoptotic cell death mechanisms like autophagy and necrosis. It also discusses the role of GADD153 in ER stress-induced apoptosis and the significance of JNK/c-Jun/AP-1 signaling pathways in cancer cell death. The review concludes with a summary model of the signaling pathways involved in anticancer drug-induced cell death and their therapeutic implications.The article discusses the impact of complex apoptotic signaling pathways on cancer cell sensitivity to therapy. It summarizes current knowledge of signaling pathways involved in anticancer drug-induced cell death, including common apoptotic and antiapoptotic pathways, non-apoptotic cell death mechanisms (autophagy, necrosis), and signaling pathways in drug-sensitive and -resistant tumor cells. The review emphasizes the role of c-Jun/activator protein 1 (AP-1) and crosstalk with mitochondrial and endoplasmic reticulum (ER) pathways. It also discusses therapeutic implications of modifying signaling pathways leading to cell death, such as targeting cell death-related genes, interactions of drug resistance factors, and the unfolded protein response (UPR) pathway. The review highlights the importance of restoring altered signaling pathways to potentially restore drug sensitivity in tumor cells. The article covers the intrinsic and extrinsic apoptotic pathways, the role of JNK in apoptosis, the antiapoptotic pathway, and non-apoptotic cell death mechanisms like autophagy and necrosis. It also discusses the role of GADD153 in ER stress-induced apoptosis and the significance of JNK/c-Jun/AP-1 signaling pathways in cancer cell death. The review concludes with a summary model of the signaling pathways involved in anticancer drug-induced cell death and their therapeutic implications.