Monoclonal antibodies for the treatment of metastatic colorectal cancer and include Cetuximab and panitumumab.
bind to the extracellular domain of the EGFR and prevent its activation by EGFR ligands such as epidermal growth factor and amphiregulin.
They inhibit the subsequent downstream signaling mediated by the RAS-RAF-extracellular signal-related kinase and phosphoinositide 3-kinase (PI3K) -phosphatase and tensin homolog (PTEN)-AKT pathways.
KRAS mutations confer inherited resistance to anti-EGFR agents and benefits in colorectal cancer is restricred to wild-type KRAS tumors.
Predictive mutations initially noted in exon 2 (codons 12 and 13) and are present in approximately 40% of patients with metastatic colon rectal cancer.
KRAS exons3 ( codons 59 and 61) and 4 (codons 117 and 146) as well as respective mutations in in NTAS found an additional 10 to 15% of colorectal tumors, predicting similar lack of response to anti-EGFR therapies.
Mutations at exon 2 at codons 12 and 13 preclude response to anti-EGFR therapy.
BRAF V600E mutations occur in 5-10% of patients with colorectal cancer are also associated with lack of benefit from EGFR monoclonal antibodies.
Mutations in BRAF, KRAS and NRAS are mutually exclusive and such patients are unlikely to benefit from standard anti-EGFR therapy.
Mutations in KRAS, NRAS, BRAF, and PIC3CA, and loss of PTEN results in resistance to anti-EGFR therapies.
HER2 amplfication is anti-EGFR antibody resisitant.
Adverse effects of these agents are: diarrhea, rash, acneiform dermatitis ,stomatitis, infusin-related reactions.
Using skin moisturizers, sunscreen, topical steroids, and doxycycline can reduce the incidence and severity of skin toxicities associated with the EGFR inhibitors