Table I.
Conventional chemotherapeutics and monoclonal antibodies used for colorectal cancer therapy.
| Chemotherapeutics | |||||
|---|---|---|---|---|---|
| Author, year | Name | Type | Mechanism of action | (Refs.) | |
| Taieb et al, 2014; | 5-Fluorouracil | Pyrimidine antimetabolite | Inhibition of thymidylate synthase activity leading to decreased DNA | (6,158–161) | |
| Alberts et al, 2012; | (5-FU) | replication and cell proliferation | |||
| Cao et al, 2015; | |||||
| Longley et al, 2003; | |||||
| Yamada et al, 2013 | |||||
| Schmoll et al, 2015 | Capecitabine | Pyrimidine antimetabolite | Inhibition of thymidylate synthase after cellular thymidine phosphorylase | (162) | |
| (5-FU prodrug) | transforms prodrug to fluorouracil | ||||
| Taieb et al, 2014; | Leucovorin | Folic acid antagonist | Increase in fluorouracil efficacy | (6,158,159,161) | |
| Alberts et al, 2012; | |||||
| Cao et al, 2015; | |||||
| Yamada et al, 2013 | |||||
| Cau et al, 2015; | Irinotecan | Topoisomerase I inhibitor | Metabolically activated in the body to 7-ethyl-10-hydroxycamptothecin | (159,163–165) | |
| Élez et al, 2015; | (SN-38 prodrug) | (SN-38) by carboxylesterase; reversible stabilization of the | |||
| Sclafani et al, 2015; | topoisomerase I complex results in single-strand DNA breaks; inhibition | ||||
| Fujita et al, 2015 | of DNA synthesis; arrest of the cell cycle at the S/G2 phase | ||||
| Taieb et al, 2014; | Oxaliplatin | DNA alkylator | Formation of crosslinks in DNA; arrest of the cell cycle in the G2/M phase; | (6,158,161,166) | |
| Alberts et al, 2012; | (platin derivative) | apoptosis induction via activation of caspases | |||
| Yamada et al, 2013; | |||||
| de Gramont et al, 2012 | |||||
| Longley et al, 2003; | Tegafur-uracil | Combinatory therapy of | Tegafur is metabolically activated in the body to 5-FU by dihydropyrimidine | (160,167) | |
| Bayoglu et al, 2015 | (UFT) | CRC with 5-FU prodrug | dehydrogenase (DPD); uracil, a competitive inhibitor of DPD, inhibits 5-FU | ||
| and uracil | catabolism and prolongs its life time; uracil decreases 5-FU doses, protecting | ||||
| patients from its toxicity | |||||
| Ben Sahra et al, 2010; | Metformine | Biguanide derivative | Activation of caspase 3; induction of apoptosis; restoration of p53 activity | (136–138) | |
| Ben Sahra et al, 2010; | Monoclonal antibodies used in combination with chemotherapeutics | ||||
| Miranda et al, 2016 | |||||
| Cao et al, 2015; | Bevacizumab | Humanized monoclonal | Blocking of the binding of all known VEGF-A isoforms to VEGF receptors; | (159,166,168–170) | |
| de Gramont et al, 2012; | IgG1 antibody | inhibition of tumor angiogenesis | |||
| Feng et al, 2014; | |||||
| Strickler et al, 2012; | |||||
| Roviello et al, 2017 | |||||
| Élez et al, 2015 | Abituzumab | Humanized monoclonal | Binding to integrin αv heterodimer; inhibition of cell binding to extracellular | (163) | |
| IgG2 antibody | matrix; inhibition of cell migration; Induction of apoptosis | ||||
| Sclafani et al, 2015 | Dalotuzumab | Humanized monoclonal | Inhibition of ligand (IGF-1, IGF-2) binding and induction of IGFR-1 | (164) | |
| IgG1 antibody | internalization and degradation; inhibition of signaling pathways responsible | ||||
| for proliferation and resistance to apoptosis | |||||
| Cunningham et al, 2004; | Cetuximab | Chimeric monoclonal | Antagonist of EGFR; prevention the signaling and ligand-induced | (4,6,158,164,171,172) | |
| Taieb et al, 2014; | IgG1 antibody | dimerization of the receptor; increases susceptibility of EGFR-positive | |||
| Alberts et al, 2012; | cells to immune cytotoxic cells; reduction in tumor growth | ||||
| Sclafani et al, 2015; | |||||
| Huang et al, 2014; | |||||
| Terazawa et al, 2017 | |||||
| Tay et al, 2015; | Panitumumab | Human monoclonal | Antagonist of EGFR; prevention of EGFR autophosphorylation and | (173,174) | |
| Bahrami et al, 2017 | IgG2 antibody | signaling; induction of apoptosis; inhibition of interleukin 8 and VEGF | |||
| production; reduction of tumor growth | |||||
| Françoso and | Ramucirumab | Humanized monoclonal | Binding of the extracellular domain of VEGF and VEGFR-2; inhibition of the | (175,176) | |
| Simioni, 2017; | IgG1 antibody | activation and signaling of VEGF/VEGFR-2; inhibition of angiogenesis | |||
| Ursem et al, 2016 | |||||
5-FU, 5-fluorouracil; EGF, epidermal growth factor; EGFR, EGF receptor; IGF-1/2, insulin-like growth factor-1/2; IGFR, IGF-1 receptor; VEGF, vascular endothelial growth factor.