Table 2.

Summary of representative anticancer agents targeting IGF-1R and RAGE against CRC.

Agent categories	References	Design	Main findings
Anticancer agents targeting IGF-1R	Leiphrakpam et al. [82]	Preclinical study	The monoclonal anti-IGF1R antibody MK-0646 and IGF-1R tyrosine kinase inhibitor OSI-906 could induce apoptosis of colon cancer cells in vitro and inhibit the growth of subcutaneous CRC xenograft.
	Cohen et al. [83]	Preclinical study	The monoclonal anti-IGF1R antibody CP751,871 could restrain the growth of CRC xenograft and enhance the anticancer efficacy of chemotherapeutic agents including Adriamycin, 5-fluorouracil, or tamoxifen in CRC models.
	Flanigan et al. [84]	Preclinical study	The IGF-1R/insulin receptor tyrosine kinase inhibitor PQIP could improve anticancer efficacy of chemotherapeutic drugs (including oxaliplatin, irinotecan, and 5-fluorocrail) against CRC xenografts.
	Becerra et al. [85]	Clinical study (n = 168)	None of the 168 patients with metastatic CRC achieved objective partial or complete response and obtain survival benefits after receiving intravenous therapy of CP751,871.
	Lin et al. [61]	Clinical study (n = 64)	Few patients with chemotherapy-refractory colorectal cancer could benefit from treatment with the monoclonal anti-IGF1R antibody SCH71745.
	Sclafani et al. [86]	Clinical study (n = 344)	Patients with metastatic CRC failed to gain survival benefits after adding monoclonal anti-IGF1R antibody MK-0646 to irinotecan and cetuximab.
	Cohen et al. [87]	Clinical study (n = 64)	The monotherapy of monoclonal anti-IGF1R antibody IMC-A12 failed to exhibit anticancer efficacy for patients with metastatic CRC. The combination of IMC-A12 with epidermal growth factor receptor inhibitor cetuximab did not show additional anticancer activity either.
	Cohn et al. [88]	Clinical study (n = 155)	Few patients with metastatic CRC refractory to fluoropyrimidine and oxaliplatin-based chemotherapy gained survival benefits from combination of monoclonal anti-IGF1R antibody AMG 479 and FOLFIRI chemotherapy.
Anticancer agents targeting RAGE	Arabiyat et al. [90]	Preclinical study	Fluoroquinolones could inhibit AGEs and exhibited cytotoxicity against multiple CRC cell lines in vitro.
	Zhang et al. [91]	Preclinical study	Flavonoids and polyphenolic acids extracted from Castanea mollissina Blume showed stronger inhibitory effects on AGEs and cytotoxic activity against CRC cell lines.
	Hafsa et al. [92]	Preclinical study	The extract from Carpobrotus edulis could inhibit AGEs and significantly decrease the CRC cell viability.
	Zhang et al. [94], 2017	Preclinical study	The anti-S100A9 antibody could suppress proliferation and inflammatory response of CRC cells in mice.
	Gnanasekar et al. [95]	Preclinical study	The short hairpin RNA targeting HMGB1 can inhibit proliferation and migration of CRC cells.
	Kuniyasu et al. [44]	Preclinical study	The HMGB1 antisense S-oligodeoxynucleotides could significantly repress growth and invasion of CRC cell lines.