title: Novel therapeutic developments other than EGFR and VEGF inhibition in colorectal cancer.
abstract: Developments that may improve existing cytotoxic therapy for colorectal cancer (CRC) include alternatives to 5-fluorouracil (5-FU) such as the liposomal Thymidylate Synthase inhibitor OSI-7904L and the multitargeted antifolate pemetrexed. Studies have explored means of reformulating irinotecan, modulating its pharmacokinetics, and enhancing its activity by maximizing DNA damage through poly(ADP-ribose) polymerase inhibition. Cell cycle inhibitors may offer an alternative to combination with 5-FU. However, as standard regimens become more complex, so do the clinical trials needed to develop new agents, and the path to registration becomes ever more tortuous. It is therefore likely that several drugs with promise in CRC will not be developed for this indication.
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, Northern Ireland, UK. r.wilson@qub.ac.uk
authors.forename: Richard H
authors.initials: RH
authors.lastname: Wilson
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005971:Glutamates / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D000068437:Pemetrexed; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005971:Glutamates; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068437:Pemetrexed; D006147:Guanine; D013940:Thymidylate Synthase; D011065:Poly(ADP-ribose) Polymerases; D066246:ErbB Receptors