Which medications may have a role in the prevention of pediatric colorectal tumors?

Updated: Jun 06, 2020
  • Author: Jaime Shalkow, MD, FACS; Chief Editor: Cameron K Tebbi, MD  more...
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Answer

Most cancers have an increased glycolytic pathway (Warburg effect). Proteomic studies have demonstrated this pathway enhancement in CRC culture cells. Bi et al also reported on decreased gluconeogenesis, suppressed glucuronic acid pathway, and an impaired tricarboxylic acid cycle. [70]  Their findings provide an insight into the tumorigenesis of CRC and possible specific targeted therapies to be developed.

Chemopreventive agents may one day inhibit the development of adenomas. Nonsteroidal anti-inflammatory drugs (NSAIDs) have a well-documented effect on shrinking existing adenomas in patients with familial adenomatous polyposis and potentially inhibit their formation. [36]

Although NSAIDs may have non–cyclooxygenase (COX)-mediated pathways, aspirin inhibits COX enzymes in the conversion of arachidonic acid to prostaglandins. COX-1 is thought to produce cytoprotective prostaglandins in the GI tract, whereas COX-2 is expressed in response to growth factors, mitogens, and cytokines and is found in 50% of colorectal adenomas and in 85% of cancers. [25]  COX-2–specific inhibition is believed to be protective against epithelial transformation. Nuclear factor kappa B (NF-κB) transcription factor translocation that produces apoptosis is another mechanism of aspirin.

Specific COX-2 inhibitors are no longer used because of their cardiovascular adverse effects. Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor-A (VEGF-A), which is believed to be critical in cancer angiogenesis. Cetuximab is another monoclonal antibody that targets the EGFR, which is involved in cancer cell proliferation, degradation of the extracellular matrix (invasiveness), tumor migration, and endothelial proliferation. It may well become a good genetic target treatment for CRC. Collaborative multi-institutional pediatric clinical trials are needed to evaluate the prognosis, optimal treatment response, and basic biology of childhood-onset CRC.


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