The Receptor Interacting Protein (RIP) kinase family consists of seven Serine/Threonine kinases

which plays a key signaling role in cell survival and cell death. Each RIP family member contains a conserved kinase domain and other domains that determine the specific kinase function through protein–protein interactions. RIP1 and RIP3 are best known for their critical roles in necroptosis

programmed necrosis and a non-apoptotic inflammatory cell death process. Dysregulation of RIP kinases contributes to a variety of pathogenic conditions such as inflammatory diseases

neurological diseases

and cancer. In cancer cells

alterations of RIP kinases at genetic

epigenetic and expression levels are frequently found

and suggested to promote tumor progression and metastasis

escape of antitumor immune response

and therapeutic resistance. However

RIP kinases can be either pro-tumor or anti-tumor depending on specific tumor types and cellular contexts. Therapeutic agents for targeting RIP kinases have been tested in clinical trials mainly for inflammatory diseases. Deregulated expression of these kinases in different types of cancer suggests that they represent attractive therapeutic targets. The focus of this review is to outline the role of RIP kinases in cancer

highlighting potential opportunities to manipulate these proteins in cancer treatment.