Serrated colorectal cancer: Molecular classification, prognosis, and response to chemotherapy

Table 2 Summary of the treatment implications of genetic alterations in colorectal cancer

Molecular marker	Implications for CRC treatment
KRAS mutation	Broadly studied in metastatic CRC
	The most predictive biomarker for no response to anti-EGFR, either alone or with CT
	Worse OS when oxaliplatin is the first-line treatment
	Irinotecan efficacy is controversial; it may have better effects in stage II and III CRC
BRAF mutation	Overall, no predictive power for CT response
	No predictive power for response to 5-FU plus irinotecan/oxaliplatin or to 5-FU alone in stage II disease
	A trend toward better survival with 5-FU plus irinotecan in stage III disease
	Effects of anti-EGFR therapy are controversial, although most studies show a poor response
	Some studies show no differences in OS/DFS with FOLFOX-panitumumab or with FOLFIRI-cetuximab treatment
	Resistance to BRAF inhibitors
CIMP	CT results are controversial
	5-FU improves DFS and OS in some studies; in others, survival is reduced
	One study shows the benefits of 5-FU plus irinotecan in CIMP tumors after stratification by MMR status. CIMP was more strongly associated than MMR status with a better response to irinotecan
	The use of 5-FU in CIMP tumors is not currently recommended
	To date, no clinical trials have evaluated the response of CIMP tumors to anti-EGFR therapy
MMR	Prognosis is intrinsically better for MSI CRC, but MSS tumors show a better response to CT
	5-FU improves both DFS and OS in stage II and III MSS CRC but not in MSI CRC
	CT should only be given for stage II MMS tumors if a high risk factor such as T4 local extension is present
	MSI CRC shows a good response to irinotecan if BAX expression has been lost

CT: Chemotherapy; DFS: Disease-free survival; anti-EGFR: Epidermal growth factor receptor antibodies; OS: Overall survival; CRC: Colorectal cancer; MMR: Mismatch repair.