Novel combination of inhibitors of WNT and MACC1 for cancer therapy
Keywords
solid tumor therapy,metastasis prevention,WNT signaling,MACC1,colorectal cancer
Invention Novelty
The discovery of a novel mechanism whereby MACC1 induces migration and metastasis via the Wnt/S100A4 axis has led to a novel combinatorial treatment strategy: inhibition of Wnt/beta-catenin signaling combined with MACC1 inhibition.
Value Proposition
Opportunity for strategic repurposing by novel, IP protected combination of established drugs in fixed-dose or single-tablet combinations. Alternative opportunity: combination with novel small molecule MACC1 inhibitors in development.
MACC1 and S100A4 as therapeutic targets for targeted treatment of cancer and for metastasis intervention.( U. Stein, Max-Delbrück-Center for Molecular Medicine)
Technology Description
In vitro proof of concept was achieved for the combination of niclosamide (representing the class of S100A4 transcriptional inhibitors) and either a statin or a MEK1 inhibitor (both representing the class of MACC1 inhibitors). Strong synergistic anti-migratory and anti-invasion effects in vitro as well as anti-metastatic effects in vivo have been observed. This potentially improves anti-metastatic therapies and allows to dose drugs at significantly lower levels, which reduces potential side-effects of chemotherapy, while simultaneously achieving stronger therapeutic efficacy.
Commercial Opportunity
Available for licensing and co-development partnerships. Strong expertise and know-how for development in CRC and metastatic CRC available to support development partnerships. Development for other indications also supported by broad patent scope.
Development Status
Preclinical: In vitro and in vivo data package available.
Patent Situation
Patent applications based on WO2020169812A1 with priority of 2019 are pending in EP, US, CA and JP.
Further Reading
Kortüm et al., Combinatorial treatment with statins and niclosamide prevents CRC dissemination by unhinging the MACC1-b-catenin-S100A4 axis of metastasis. Oncogene, 2022. https://doi.org/10.1038/s41388-022-02407-6
Gohlke et al., Real-world evidence for preventive effects of statins on cancer incidence: A trans-Atlantic analysis, Clin Transl Med, 2022. https://doi.org/10.1002/ctm2.726
Kobelt et al., The newly identified MEK1 tyrosine phosphorylation target MACC1 is druggable by approved MEK1 inhibitors to restrict colorectal cancer metastasis, Oncogene, 2021. https://doi.org/10.1038/s41388-021-01917-z
Juneja et al., Statin and rottlerin small-molecule inhibitors restrict colon cancer progression and metastasis via MACC1, PLOS Biology 2017. https://doi.org/10.1371/journal.pbio.2000784
Sack et al., Novel effect of antihelminthic Niclosamide on S100A4-mediated metastatic progression in colon cancer, J Natl Cancer Inst, 2011. doi.org/10.1093/jnci/djr190
Institute of Origin
