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Table 1 Properties of the chemotherapeutic drugs used in AML

From: Deciphering molecular mechanisms underlying chemoresistance in relapsed AML patients: towards precision medicine overcoming drug resistance

Drug Target Influx Metabolisma Efflux Refs.
Cytarabine (Ara-C) DNA polymerases ENT1, CNT3, OCTN1 Activation: dCK, dCMPK, NDK. Inactivation: CDA, dCMPD, PN-I. MRP4,7,8 [14, 30,31,32,33, 78,79,80]
Daunorubicin (DNR) DNA, Topoisomerase II Passive diffusion   P-gp, MRP1,7, BCRP [44, 51, 81,82,83,84]
Mitoxantrone (MX) DNA, Topoisomerase II Passive diffusion   P-gp, MRP1, BCRP [44, 85,86,87,88,89,90]
Etoposide (VP-16) Topoisomerase II Passive diffusion   P-gp, MRP1-3,6, BCRP [16, 91, 92]
Methotrexate (MTX) DHFR, TS, AICARFT RFC, PCFT Aldehyde oxidase, FPGS (polyglutamylation) P-gp, MRP1-5, BCRP [16, 93, 94]
Venetoclax (VEN) Bcl-2 Passive diffusion   P-gp [72, 95]
Gemtuzumab Ozogamicin (GO) DNA Ab-mediated endocytosis Lysosomal Calicheamicin cleavage from Ab, glutathione P-gp, MRP1 [73, 77]
  1. DHFR, dihydrofolate reductase; TS, thymidylate synthase; AICARFT, aminoimidazole-4-carboxamide ribonucleotide formyltransferase; Bcl-2, B-cell leukemia/lymphoma 2; ENT1, equilibrative nucleoside transporter 1; CNT3, concentrative nucleoside transporter 3; OCTN1, organic cation transporter, novel, type 1; RFC, reduced folate carrier; PCFT, proton coupled folate transporter; dCK, deoxycytidine kinase; dCMPK, deoxycytidylate kinase; NDK, nucleoside diphosphate kinase; CDA, cytidine deaminase; dCMPD, deoxycytidylate deaminase; PN-I, cytosolic 5-nuleotidase 3A; FPGS, folylpoly-ɣ-glutamate synthetase; MRP, multidrug resistance-associated protein; P-gp, P-glycoprotein; BCRP, breast cancer resistance protein.
  2. aOccuring in leukemic cells.