RIPK1 kinase and scaffold activities in tumor cell fate and therapy

Receptor-interacting protein kinase 1 (RIPK1) plays a pivotal role in regulating cell survival and death, thereby exerting complex and multifaceted functions in the initiation and progression of cancer. Its expression is frequently dysregulated across diverse malignancies and correlates strongly with poor prognosis, highlighting its significance in the tumor microenvironment. The precise mechanisms through which RIPK1 modulates oncogenic processes, including cell death pathways, immune evasion, proliferation, migration, and drug resistance, remain incompletely elucidated, presenting both a challenge and an opportunity. This review summarizes the molecular mechanisms orchestrated by RIPK1, discusses its expression profiles across human cancers, and analyzes relevant regulatory networks. We also highlight recent advances in targeting RIPK1 therapeutically, focusing on emerging strategies such as small-molecule inhibitors and proteolysis-targeting chimera (PROTAC). We evaluate the translational potential of these agents, particularly in immunotherapy and chemosensitization. By synthesizing the multifaceted roles of RIPK1 in malignancy, this article hopes to identify novel therapeutic vulnerabilities for precision oncology.