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. 2020 Mar 2;19:50. doi: 10.1186/s12943-020-01169-7

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 3 — The metabolism and mechanisms of gemcitabine action. Gemcitabine plays an anticancer role after a series of phosphorylations in pancreatic cancer cells. Asterisks indicate that dFdCTP is the most active metabolite of gemcitabine that produces anticancer effects. Intermediates in gray ovals have anticancer functions. Long solid arrows represent shifts or bioconversions. Dotted arrows mean positive regulations, while dotted blunt ends mean negative regulations. dFdC, 2’,2’-difluorodeoxycytidine (gemcitabine); dFdCMP, 2’,2’-difluorodeoxycytidine 5’-monophosphate; dFdCDP, 2’,2’-difluorodeoxycytidine 5’-diphosphate; dFdCTP, 2’,2’-difluorodeoxycytidine 5’-triphosphate; dFdU, 2’,2’-difluorodeoxyuridine; dFdUMP, 2’,2’-difluorodeoxyuridine 5’-monophosphate; dFdUDP, 2’,2’-difluorodeoxyuridine 5’-diphosphate; dFdUTP, 2’,2’-difluorodeoxyuridine 5’-triphosphate; dUMP, deoxyuridine monophosphate; dTMP, deoxythymidine monophosphate; dTTP, deoxythymidine triphosphate; CDP, cytidine diphosphate; dCDP, deoxycytidine diphosphate; dCTP, deoxycytidine triphosphate; CDA, cytidine deaminase; dCK, deoxycytidine kinase; DCTD, deoxycytidylate deaminase; hNTs, human nucleosides transporters; NDPK, nucleoside diphosphate kinase; NMPK, nucleoside monophosphate kinase; RR, ribonucleotide reductase; TS, thymidylate synthase; 5’-NT, 5’-nucleotidase