The article discusses the targeting of apoptotic pathways for cancer therapy, focusing on intrinsic and extrinsic pathways, as well as the p53 and integrated stress response (ISR) pathways. Apoptosis, a form of programmed cell death, is crucial for preventing cancer, but cancer cells often evade apoptosis through various mechanisms, including the overexpression of anti-apoptotic proteins and the inhibition of pro-apoptotic signals. The article reviews current and emerging therapies that aim to restore or enhance apoptosis in cancer cells. Key therapeutic strategies include BCL-2 inhibitors, such as venetoclax, which target the BCL-2 family of proteins to promote apoptosis. Venetoclax has shown promise in treating chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). TRAIL analogs and DR4/5 agonist antibodies are also discussed, with some showing potential in clinical trials, although challenges such as short half-life and limited efficacy remain. The article also explores the role of p53 in apoptosis, highlighting the development of compounds that can reactivate mutant p53 or inhibit its negative regulators. Additionally, the use of ISR activators, such as imipridones, is discussed, as they can induce apoptosis through the upregulation of pro-apoptotic genes. The article also addresses resistance mechanisms in cancer cells, including the role of the proteasome and the integrated stress response. Proteasome inhibitors like bortezomib and carfilzomib are discussed, as they induce ER stress and activate the ISR, leading to apoptosis. However, resistance to these drugs can develop, necessitating the exploration of combination therapies and novel approaches to overcome resistance. In conclusion, targeting apoptotic pathways represents a promising approach in cancer therapy, with ongoing research aimed at developing more effective and targeted treatments. The article highlights the importance of understanding the complex interactions within apoptotic pathways and the need for innovative strategies to overcome resistance and improve patient outcomes.The article discusses the targeting of apoptotic pathways for cancer therapy, focusing on intrinsic and extrinsic pathways, as well as the p53 and integrated stress response (ISR) pathways. Apoptosis, a form of programmed cell death, is crucial for preventing cancer, but cancer cells often evade apoptosis through various mechanisms, including the overexpression of anti-apoptotic proteins and the inhibition of pro-apoptotic signals. The article reviews current and emerging therapies that aim to restore or enhance apoptosis in cancer cells. Key therapeutic strategies include BCL-2 inhibitors, such as venetoclax, which target the BCL-2 family of proteins to promote apoptosis. Venetoclax has shown promise in treating chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). TRAIL analogs and DR4/5 agonist antibodies are also discussed, with some showing potential in clinical trials, although challenges such as short half-life and limited efficacy remain. The article also explores the role of p53 in apoptosis, highlighting the development of compounds that can reactivate mutant p53 or inhibit its negative regulators. Additionally, the use of ISR activators, such as imipridones, is discussed, as they can induce apoptosis through the upregulation of pro-apoptotic genes. The article also addresses resistance mechanisms in cancer cells, including the role of the proteasome and the integrated stress response. Proteasome inhibitors like bortezomib and carfilzomib are discussed, as they induce ER stress and activate the ISR, leading to apoptosis. However, resistance to these drugs can develop, necessitating the exploration of combination therapies and novel approaches to overcome resistance. In conclusion, targeting apoptotic pathways represents a promising approach in cancer therapy, with ongoing research aimed at developing more effective and targeted treatments. The article highlights the importance of understanding the complex interactions within apoptotic pathways and the need for innovative strategies to overcome resistance and improve patient outcomes.