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Ref Type Journal Article
PMID (25605917)
Authors Li Y, Rogoff HA, Keates S, Gao Y, Murikipudi S, Mikule K, Leggett D, Li W, Pardee AB, Li CJ
Title Suppression of cancer relapse and metastasis by inhibiting cancer stemness.
Journal Proceedings of the National Academy of Sciences of the United States of America
Vol 112
Issue 6
Date 2015 Feb 10
URL
Abstract Text Partial or even complete cancer regression can be achieved in some patients with current cancer treatments. However, such initial responses are almost always followed by relapse, with the recurrent cancer being resistant to further treatments. The discovery of therapeutic approaches that counteract relapse is, therefore, essential for advancing cancer medicine. Cancer cells are extremely heterogeneous, even in each individual patient, in terms of their malignant potential, drug sensitivity, and their potential to metastasize and cause relapse. Indeed, hypermalignant cancer cells, termed cancer stem cells or stemness-high cancer cells, that are highly tumorigenic and metastatic have been isolated from cancer patients with a variety of tumor types. Moreover, such stemness-high cancer cells are resistant to conventional chemotherapy and radiation. Here we show that BBI608, a small molecule identified by its ability to inhibit gene transcription driven by Stat3 and cancer stemness properties, can inhibit stemness gene expression and block spherogenesis of or kill stemness-high cancer cells isolated from a variety of cancer types. Moreover, cancer relapse and metastasis were effectively blocked by BBI608 in mice. These data demonstrate targeting cancer stemness as a novel approach to develop the next generation of cancer therapeutics to suppress cancer relapse and metastasis.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Napabucasin Napabucasin 4 9
Drug Name Trade Name Synonyms Drug Classes Drug Description
Napabucasin BB608|BBI608|BBI-608 STAT3 Inhibitor 19 Napabucasin (BBI608) is a small molecule inhibitor of cancer “stemness” that reduces activated Stat3 signaling, which is often activated by FGFRs, thereby decreasing proliferation of cancer stem cells, and possibly resulting in decreased cancer metastasis (PMID: 25605917, PMID: 23935373).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown pancreatic cancer not applicable Napabucasin Preclinical Actionable In a preclinical study, BBI608 inhibited tumor growth and metastasis in xenograft models of pancreatic cancer (PMID: 25605917). 25605917