Repurposing of Antibiotics for treating APC (Adenomatous Polyposis Coli) Related Colorectal Cancer

Restoration of Adenomatous Polyposis Coli (APC) gene expression by means of antibiotic erythromycin for the treatment of Familial Adenomatous Polyposis.

The Technology:
Treatment for APC by   conventional antibiotics to regulate adenoma growth and delay the need for preventive surgery in Familial Adenomatous Polyposis (FAP) patients. 

The Need: 
FAP is a high penetrance devastating syndrome manifested by dozens to thousands of colonic adenomas. Most FAP cases are attributed to inherited mutations in the APC gene, as was observed in both hereditary and sporadic colorectal cancer (CRC). Multiple chemoprevention trials have been performed to postpone or prevent surgery in FAP patients. However, none of them are currently routinely employed in clinical practice as they were shown to be ineffective or to have strong side effects. Our technology can restore APC expression by means of antibiotic (Erythromycin and Azithromycin) treatment, resulting in adenoma growth stabilization and/or regression, and potentially assist in postponing or even preventing surgery and cancer development. 
• Pharmacological chemo-preventive solution for colorectal cancer
• Personalized approach for slowing tumor growth and cancer progression, depending on the type of germline mutation
• Repurposing of common antibiotics/drugs
• Prevention or delay of the inevitable surgery in polyposis patients
Our innovation:
• Effective method for reduction of FAP load (number and size)
• Requires only conventional broad-spectrum antibiotics (erythromycin and azithromycin)   
• Previously approved and used in the healthcare industry

 Current Results:   
Ten (10) FAP patients harboring APC nonsense mutations were treated with the read-through inducing antibiotic erythromycin for four (4) months Our results show that in the majority of patients the treatment led to a decrease in cumulative adenoma burden, median reduction in cumulative adenoma size and median reduction in adenoma number (Fig. 1). Seven of the ten patients responded to the treatment according to the posttreatment colonoscopy (at 4 months) and exhibited a reduction in the number and cumulative size of adenomas. A reduction at follow up endoscopy (12 months) was observed in six patients, four of whom were initial responders.  Molecular and genetic analyses of the adenomas revealed that the treatment led to a reduced number of somatic APC mutations, reduced cellular proliferation and restoration of APC tumor-suppressing activity.
US 9,486,467 (extended by 1196 days) granted
WO 2007/144876, granted in Europe 
1. Kariv R, Caspi M, Fliss-Isakov N, Shorer Y, Shor Y, Rosner G, Brazowski E, Beer G, Cohen S, Rosin-Arbesfeld R. Resorting the function of the colorectal cancer (CRC) gate keeper adenomatous Polyposis Coli (APC). Int J Cancer. 2019 Jul 8 

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