Gastrointestinal Disasters of Cetuximab in the Treatment of Metastatic Colorectal Cancer: Mechanism and its Effect on Prognosis
Colorectal cancer (CRC) is among the top three cancers worldwide in terms of incidence and associated mortality. Colorectal cancer (CRC) is responsible for more than 880,000 deaths annually. The number of of CRC cases worldwide continues to increase, posing a serious threat to human health. Surgery and chemotherapy are the first treatments for CRC patients. The majority of CRC patients are diagnosed at an advanced stage, as symptoms are usually not apparent and difficult to diagnose in the early stage. The prognosis of metastatic CRC (mCRC) has long been unsatisfactory. Targeted drugs therapy, which targeting at specific genes and proteins, is a new treatment approach to CRC. Cetuximab is one of the most widely studied targeted drugs. By competitively binding to the epithelial growth factor receptor (EGFR), cetuximab inhibits the EGF and binding of the EGF ligand to the EGFR, thereby inhibiting tumor cell growth, invasion, and metastasis and inducing tumor cell apoptosis. The curative effect of cetuximab as a treatment for many kinds of tumors, especially mCRC, has been confirmed. Cetuximab combined with chemotherapy or monotherapy is used as first-line treatment in patients with RAS(rat sarcoma,Ras) wild-type mCRC. However, adverse drug reactions (ADRs) associated with the clinical application of cetuximab are attracting increasing attention, with numerous studies reporting adverse effects of cetuximab on the gastrointestinal system, with these effects having adverse consequences for the prognosis of CRC. In this review, we focus mainly on gastrointestinal disasters on cetuximab treatment for mCRC from three areas: the intestinal mucosal barrier (IMB), gut microbiota (GM)-host immune balance, and bacterial metabolites short chain fatty acids (SCFAs), and the impact of these effects on the prognosis of mCRC. We also make suggestions aimed at aiding oncological understanding of cetuximab as a treatment for mCRC.
Keywords: Bacterial metabolites, cetuximab, colorectal cancer, gut microbiota-host immune balance, gastrointestinal disasters