New Way to Fight Cancer Unveiled in Study

     (CN) — Researchers have developed an inhibitor that could be used as a new therapy option for patients with colorectal cancer, which kills about 700,000 people annually worldwide.
     Created by a team from multiple Japanese institutions, the inhibitor would be particularly useful for patients with drug-resistant colorectal cancer.
     Their findings were published Friday in the journal Nature Communications.
     The researchers developed a novel small-molecule Wnt inhibitor named NCB-0846. Wnt signaling is a key pathway of cancer stem-cell progress.
     Over 90 percent of colorectal cancers carry somatic mutations in Wnt signaling component genes, such as adenomatous polyposis coli, or APC, a tumor suppressor gene.
     The activation of Wnt signaling leads to the generation of cancer stem cells, which are inherently resistant to conventional chemotherapy. Therefore, therapies that can block Wnt signaling are likely to eliminate cancer stem cells and cure the disease.
     Despite a wealth of data and investment in research and development, no Wnt-inhibit drug has been used in clinical practice.
     The team screened a kinase-focused — an enzyme that transfers energy from a high-energy donor molecule to specific, target molecules — compound library, which led to the discovery of NCB-0846.
     The new inhibitor was orally administrable and suppressed the growth of patient-derived colorectal cancer xenografts, which are a tissue graft or organ transplant from a donor of a different species from the recipient. NCB-0846 suppressed various cancer stem cell activities of colorectal cancer cells and their expression of markers.
     “We’re very encouraged by our promising preclinical data for NCB-0846, especially considering the difficulty in targeting this pathway to date, and shortly we hope to conduct a clinical trial at the NCC hospitals,” said co-author Tesshi Yamada.

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