RIPK2: a promising target for cancer treatment

Abstract

As an essential mediator of inflammation and innate immunity, the receptor-interacting serine/threonine-protein kinase-2 (RIPK2) is responsible for transducing signaling downstream of the intracellular peptidoglycan sensors nucleotide oligomerization domain (NOD)-like receptors 1 and 2 (NOD1/2), which will further activate nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, leading to the transcription activation of pro-inflammatory cytokines and productive inflammatory response. Thus, the NOD2-RIPK2 signaling pathway has attracted extensive attention due to its significant role in numerous autoimmune diseases, making pharmacologic RIPK2 inhibition a promising strategy, but little is known about its role outside the immune system. Recently, RIPK2 has been related to tumorigenesis and malignant progression for which there is an urgent need for targeted therapies. Herein, we would like to evaluate the feasibility of RIPK2 being the anti-tumor drug target and summarize the research progress of RIPK2 inhibitors. More importantly, following the above contents, we will analyze the possibility of applying small molecule RIPK2 inhibitors to anti-tumor therapy.

New approaches and prospects of immunotherapy and gene therapy for prostate cancer

“…Additionally, it plays a role in the advancement and metastasis of prostate cancer by maintaining c-Myc, a protein that promotes tumor development and invasiveness. Therefore, interventions targeting RIPK2 to degrade c-Myc, such as medicines or gene editing techniques, may hold promise in preventing prostate cancer [220,221] . Some research suggests that RIPK2 inhibitors have shown beneficial effects in both preclinical and clinical trials.…”

“…For instance, the small molecule inhibitor ALW-II-41-27 binds to the ATP-binding site of RIPK2, impeding its kinase activity. Studies conducted in vitro and in vivo have demonstrated its efficacy in inhibiting the proliferation and invasion of prostate cancer cells [220] . Another approach involves KB004, a humanized monoclonal antibody that induces internalization and degradation of RIPK2 by recognizing an epitope on its extracellular domain.…”

“…Another obstacle is the variability in RIPK2 expression and function across various subtypes and stages of prostate cancer. In various prostate cancer cells, RIPK2 expression levels can range from high to low, or even absent, and its function can change from proangiogenic to antiangiogenic as tumors progress [220] . As a result, RIPK2-targeted medicines should be carefully tailored in terms of timing and dosage to accommodate the unique characteristics of each patient.…”