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Review
. 2016 Jan;8(1):57-84.
doi: 10.1177/1758834015614530.

Pharmacologic resistance in colorectal cancer: a review

William A Hammond  1 , Abhisek Swaika  1 , Kabir Mody  2
Affiliations
Review

Pharmacologic resistance in colorectal cancer: a review

William A Hammond et al. Ther Adv Med Oncol. 2016 Jan.

Abstract

Colorectal cancer (CRC) persists as one of the most prevalent and deadly tumor types in both men and women worldwide. This is in spite of widespread, effective measures of preventive screening, and also major advances in treatment options. Despite advances in cytotoxic and targeted therapy, resistance to chemotherapy remains one of the greatest challenges in long-term management of incurable metastatic disease and eventually contributes to death as tumors accumulate means of evading treatment. We performed a comprehensive literature search on the data available through PubMed, Medline, Scopus, and the ASCO Annual Symposium abstracts through June 2015 for the purpose of this review. We discuss the current state of knowledge of clinically relevant mechanisms of resistance to cytotoxic and targeted therapies now in use for the treatment of CRC.

Keywords: colon adenocarcinoma; colon cancer; resistance.

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Conflict of interest statement

Conflict of interest statement: The author(s) declare(s) that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Schematic representation of the fluoropyrimidine pathway. 5,10-CH2-FH4, 5,10-methylenetetrahydrofolate; 5-CH3-FH4, 5-methyltetrahydrofolate; 5’dFCR, 5’-deoxy-5- fluorocytidine; 5’dFUR, 5’-deoxy-5-fluorouridine; 5-FdUDP, 5-fluorodeoxyuridine diphosphate; 5-FdUMP, 5- fluorodeoxyuridine monophosphate; 5-FdUTP, 5-fluorodeoxyuridine triphosphate; 5-FU, 5-fluorouracil; 5- FUDP, 5-fluorodeoxyuridine; 5-FUDR, 5-fluorodeoxyuridine, 5-FUMP,5-fluorouridine monophosphate; 5- FUR, 5-fluorouridine; 5-FUTP, 5-fluorouridine triphosphate; CDHP, 5-chloro-2,4-dihydroxypyridine; DHFU, dihydrofluorouracil; DPD, dihydropyrimidine dehydrogenase; dTTP, deoxythymidine triphosphate; FBAL, fluoro-β-alanine; FH4, tetrahydrofolate; FH2, dihydrofolate; FUPA, α-fluoro-β-ureidopropionic acid; NDK, nucleoside diphosphate kinase; ORPT, orotate phosphoribosyltransferase; TFT, trifluorothymidine; TFT-MP, trifluorothymidine monophosphate; TFT-TP, trifluorothymidine triphosphate; TK, thymidine kinase; UMP-CMPK, uridine monophosphate-cytidine monophosphate kinase.
Figure 2.
Figure 2.
Schematic representation of the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) and receptor (VEGF-R) pathways. BAD, Bcl-2 associated death promotor; EGF, epidermal growth factor; EIF-4, eukaryotic initiation factor-4; Grb2,growth factor receptor bound protein 2; MAPK, mitogen activated protein kinase; MEK, mitogen/extracellular signal related kinase; mTOR, mammalian target of rapamycin; MDM2, mouse double minute 2; NFκB, nuclear factor κ-light chain enhancer of activated B cells; TGF-α, transforming growth factor alpha; TF, transcription factor; P, phosphate; PI3K, phosphoinositide 3 kinase; PIP2, phosphatidylinositol (4, 5)-bisphosphate; PIP3, phosphatidylinositol (3,4,5)-triphosphate; RAS, rat sarcoma; RAF, rapidly accelerated fibrosarcoma; SOS, son of sevenless.
See this image and copyright information in PMC

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