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guadecitabine + nivolumab
- Development stage
- Discontinued
- Lead developer
- Astex Pharmaceuticals
- Modality
- Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
- Administration
- Subcutaneous, Intravenous
01
Overview
A combination therapy consisting of guadecitabine, a next-generation DNA methyltransferase (DNMT) inhibitor, and nivolumab, a monoclonal antibody targeting the programmed death-1 (PD-1) receptor. Guadecitabine is a hypomethylating agent designed to be resistant to degradation by cytidine deaminase, thereby extending the exposure of its active metabolite, decitabine. In the context of colorectal adenocarcinoma, particularly the CpG Island Methylator Phenotype (CIMP+) subtype, guadecitabine is used to reverse epigenetic silencing of genes, potentially enhancing the immunogenicity of the tumor and overcoming resistance to immunotherapy. Nivolumab works by blocking the PD-1/PD-L1 pathway, allowing T-cells to recognize and attack tumor cells. This combination is being investigated for its synergistic potential in treating refractory metastatic colorectal cancer.
- Other names
- Guadecitabine and Nivolumab
02
Targets
DNMT1 (DNA (cytosine-5)-methyltransferase 1)PDCD1 (Programmed cell death protein 1 receptor)
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