HomeENGLISH MAGAZINEFamiliar polyposis prevention: beside NSAIDs, antibiotics seem effective

Familiar polyposis prevention: beside NSAIDs, antibiotics seem effective

Researchers from Tel Aviv University and Tel Aviv Sourasky Medical Center (Ichilov Hospital) have developed an innovative drug treatment for familial adenomatous polyposis (FAP), a rare, inherited condition that affects adolescents and young adults and often leads to colorectal cancer. FAP, which is characterized by multiple polyps along the gastrointestinal tract, especially in the large bowel, is caused by a mutation in the adenomatous polyposis coli (APC) gene. These mutations are also crucial for colorectal cancer development. In its normal state, APC promotes the production of a protein that inhibits cancer development. But mutations to the APC gene produce an inactive protein that is unable to prevent the development of the polyps. In some FAP patients, the mutations in the APC gene are what are called “nonsense mutations. Each sequence of three nucleotides in the DNA is a code that tells the cell to produce a certain amino acid, which are the building blocks of the proteins produced in the body’s cells. At the end of the protein coding sequence, there is usually a ‘stop codon’ to stop the protein production. But in FAP patients with a nonsense mutation, the APC’s stop codon appears prematurely, so the protein production stops prematurely, creating an inactive protein.

To prevent the development of colorectal cancer, FAP patients are closely monitored via frequent colonoscopies to locate and remove their polyps. However, some patients must have their colons removed at a very young age, which dramatically affects their quality of life. One but a pharmacological treatment exists for FAP prevention: the cyclical administration of inhibitors oc cyclo-oxigenase pathway as NSAIDs. Aspirin was the first tested and approved, but coxib drugs are preferred for their specificity on the COX2 enzyme. COX2-derived prostaglandin E2 has indeed pro-inflammatory and promoter effect on the polyp mucosal cells. The novel drug, based on antibiotics, inhibits the development of intestinal polyps that, left untreated, become cancerous. In a preliminary clinical trial, the condition of seven out of eight patients who completed the full treatment improved dramatically. The research was jointly led by Prof. Rina Rosin-Arbesfeld of the Department of Microbiology and Clinical Immunology at TAU’s Sackler School of Medicine and Prof. Revital Kariv of the Sackler School and the Department of Gastroenterology at Tel Aviv Sourasky Medical Center. It was published on July 8 in the International Journal of Cancer. Previous experiments on cell cultures and mouse models in Prof.

Rosin-Arbesfeld’s laboratory revealed that certain types of antibiotics caused cells to “ignore” the mutation stop codon and a normal protein resulted. These trials yielded promising results that led to the clinical trial at Tel Aviv Sourasky Medical Center. Since the relevant antibiotics were already approved for human use, the team decided to move directly from the laboratory to the clinic and to examine the treatment of FAP patients. In the clinical study carried out by Prof. Kariv and Dr. Shlomi Cohen, director of the Pediatric Gastroenterology Unit at Dana-Dwek Children’s Hospital, 10 FAP patients received the novel antibiotic therapy. Eight of them completed the treatment, which lasted four months. Colonoscopies performed during and after the treatment showed that in seven patients the polyps significantly decreased in number. Moreover, the positive effects of the treatment were evident a year after it began. The researchers recently won Tel Aviv University’s SPARK grant, which supports the development of applied research. Prof. Kariv concluded: “Our goal as therapists, in addition to preventing cancer, is to improve the quality of life of our patients and their families and to enable them to live as full and normal lives as possible. The new therapeutic approach we are developing may allow patients to delay surgical intervention or even prevent it entirely”.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Kariv R et al., Rosin-Arbesfeld R. Int J Cancer. 2019 Jul 8. 

Liu X, Wang X et al. Med Sci Monit. 2018 Nov 10; 24:8048-55.

Kaur K et al., Chanda A. Cancer Med. 2018; 7(5):2003-2012. 

Pinsk V et al., Ling E. Anticancer Res. 2017; 37(6):3105-3109.

Dott. Gianfrancesco Cormaci
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di due brevetti sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of patents concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica e salute sui siti web salutesicilia.com, medicomunicare.it e in lingua inglese sul sito www.medicomunicare.com
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