New mechanisms of multidrug resistance: an introduction to the Cancer Drug Resistance special collection

Abstract

Cancer Drug Resistance publishes contributions to understanding the biology and consequences of mechanisms that interfere with successful treatment of cancer. Since virtually all patients who die of metastatic cancer have multidrug-resistant tumors, improved treatment will require an understanding of the mechanisms of resistance to design therapies that circumvent these mechanisms, exploit these mechanisms, or inactivate these multidrug resistance mechanisms. One example of a resistance mechanism is the expression of ATP-binding cassette efflux pumps, but unfortunately, inhibition of these transporters has not proved to be the solution to overcome multidrug resistance in cancer. Other mechanisms that confer multidrug resistance, and the confluence of multiple different mechanisms (multifactorial multidrug resistance) have been identified, and it is the goal of this Special Collection to expand this catalog of potential multidrug resistance mechanisms, to explore novel ways to overcome resistance, and to present thoughtful reviews on the problem of multidrug resistance in cancer.

Keywords

Cancer drug resistance / multidrug resistance / ABC transporters / novel mechanisms of drug resistance

References

[1] Gottesman MM,Hall MD.Toward a better understanding of the complexity of cancer drug resistance.Annu Rev Pharmacol Toxicol2016;56:85-102

[2] Hanahan D.Hallmarks of cancer: new dimensions.Cancer Discov2022;12:31-46

[3] Recasens A.Targeting cancer cell dormancy.Trends Pharmacol Sci2019;40:128-41

[4] Hangauer MJ,Ryan MJ.Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition.Nature2017;551:247-50 PMCID:PMC5933935

[5] Alexa-Stratulat T,Gašparović AČ,Riganti C.What sustains the multidrug resistance phenotype beyond ABC efflux transporters? Looking beyond the tip of the iceberg.Drug Resist Updat2019;46:100643

[6] Jena BC,Bharadwaj D.Cancer associated fibroblast mediated chemoresistance: a paradigm shift in understanding the mechanism of tumor progression.Biochim Biophys Acta Rev Cancer2020;1874:188416

[7] Sanchez-Burgos L,García-Martín S.Activation of the integrated stress response is a vulnerability for multidrug-resistant FBXW7-deficient cells.EMBO Mol Med2022;14:e15855 PMCID:PMC9449593

[8] Zhang H,Liu X.Progress of long noncoding RNAs in anti-tumor resistance.Pathol Res Pract2020;216:153215

[9] He C,Sun B,Xiao ZD.Microvesicles: the functional mediators in sorafenib resistance.Cancer Drug Resist2022;5:749-61 PMCID:PMC9511799

[10] Shaffer SM,Torborg SR.Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance.Nature2017;546:431-5 PMCID:PMC5542814

[11] Roy S.Microbiota: a key orchestrator of cancer therapy.Nat Rev Cancer2017;17:271-85

[12] Afasizheva A,Tillman H.Mitogen-activated protein kinase signaling causes malignant melanoma cells to differentially alter extracellular matrix biosynthesis to promote cell survival.BMC Cancer2016;16:186 PMCID:PMC4779217

[13] Kuenzi BM,Fong SH.Predicting drug response and synergy using a deep learning model of human cancer cells.Cancer Cell2020;38:672-84.e6 PMCID:PMC7737474

[14] Borst P.Cancer drug pan-resistance: pumps, cancer stem cells, quiescence, epithelial to mesenchymal transition, blocked cell death pathways, persisters or what?.Open Biol2012;2:120066 PMCID:PMC3376736

[15] Rottenberg S,Pajic M.Selective induction of chemotherapy resistance of mammary tumors in a conditional mouse model for hereditary breast cancer.Proc Natl Acad Sci U S A2007;104:12117-22 PMCID:PMC1914039

[16] Zander SA,van der Burg E.Sensitivity and acquired resistance of BRCA1;p53-deficient mouse mammary tumors to the topoisomerase I inhibitor topotecan.Cancer Res2010;70:1700-10

[17] Bakhsheshian J,Chang KE.Bioluminescent imaging of drug efflux at the blood-brain barrier mediated by the transporter ABCG2.Proc Natl Acad Sci U S A2013;110:20801-6 PMCID:PMC3870704

[18] Robey RW,Hall MD,Bates SE.Revisiting the role of ABC transporters in multidrug-resistant cancer.Nat Rev Cancer2018;18:452-64 PMCID:PMC6622180

[19] Frye WJE,Gonzalez Dalmasy JM et al.The multidrug resistance transporter P-glycoprotein confers resistance to ferroptosis inducers.Cancer Drug Resist2023;6:468-80

[20] Borst P.Looking back at multidrug resistance (MDR) research and ten mistakes to be avoided when writing about ABC transporters in MDR.FEBS Lett2020;594:4001-11

[21] Luria SE.Mutations of bacteria from virus sensitivity to virus resistance.Genetics1943;28:491-511 PMCID:PMC1209226

[22] Chen KG,Mogul MJ.Genomic stability at the coding regions of the multidrug transporter gene ABCB1: insights into the development of alternative drug resistance mechanisms in human leukemia cells.Cancer Drug Resist2020;3:959-79 PMCID:PMC8445225

[23] Horibata S,Lack J,Gottesman MM.Heterogeneity in refractory acute myeloid leukemia.Proc Natl Acad Sci U S A2019;116:10494-503 PMCID:PMC6535032

[24] Klco JM,Miller CA.Functional heterogeneity of genetically defined subclones in acute myeloid leukemia.Cancer Cell2014;25:379-92 PMCID:PMC3983786

[25] Goyal Y,Pillai M.Diverse clonal fates emerge upon drug treatment of homogeneous cancer cells.Nature2023;620:651-9

[26] Alyateem G,Bickert AA.Use of CRISPR-based screens to identify mechanisms of chemotherapy resistance.Cancer Gene Ther2023;30:1043-50

[27] Eyler CE,Hovestadt V,van Galen P.Single-cell lineage analysis reveals genetic and epigenetic interplay in glioblastoma drug resistance.Genome Biol2020;21:174 PMCID:PMC7364565

[28] Gillet JP,Varma S.Redefining the relevance of established cancer cell lines to the study of mechanisms of clinical anti-cancer drug resistance.Proc Natl Acad Sci U S A2011;108:18708-13 PMCID:PMC3219108

[29] Hotz JM,Katz EN,Horibata S.ATP-binding cassette transporters at the zebrafish blood-brain barrier and the potential utility of the zebrafish as an in vivo model.Cancer Drug Resist2021;4:620-33 PMCID:PMC8297714

[30] Grossman JE,Huang L.Organoid sensitivity correlates with therapeutic response in patients with pancreatic cancer.Clin Cancer Res2022;28:708-18 PMCID:PMC8866201