Targeting necroptosis in anticancer therapy: mechanisms and modulators

Necroptosis, a genetically programmed form of necrotic cell death, serves as an important pathway in human diseases. As a critical cell-killing mechanism, necroptosis is associated with cancer progression, metastasis, and immunosurveillance. Targeting necroptosis pathway by small molecule modulators is emerging as an effective approach in cancer therapy, which has the advantage to bypass the apoptosis-resistance and maintain antitumor immunity. Therefore, a better understanding of the mechanism of necroptosis and necroptosis modulators is necessary to develop novel strategies for cancer therapy. This review will summarize recent progress of the mechanisms and detecting methods of necroptosis. In particular, the relationship between necroptosis and cancer therapy and medicinal chemistry of necroptosis modulators will be focused on.