Mechanisms of Multidrug Resistance in Cancer Chemotherapy
Abstract
:1. Introduction
2. Types of Chemotherapeutics
3. The Problem of Drug Resistance in Cancer Chemotherapy
3.1. Enhanced Efflux of Drugs
3.2. Genetic Factors
3.2.1. Gene Mutations
3.2.2. Amplifications
3.2.3. Epigenetic Alterations
3.3. Growth Factors
3.4. Increased DNA Repair Capacity
3.5. Elevated Metabolism of Xenobiotics
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ABC | ATP-binding cassette |
ATR | Ataxia telangiectasia and Rad3-related protein |
5-FU | 5-Fluorouracil |
BCRP | Human breast cancer resistance protein |
BBB | Blood–brain barrier |
BRCA | Breast cancer gene |
CAF | Chromatin assembly factor-1 |
CD24 | Glycosylphosphatidylinositol-linked cell surface glycoprotein gene |
CDK 4/6 | Cyclin-dependent kinase 4/6 |
CML | Chronic myeloid leukemia |
CYP | Cytochrome |
DDR | DNA-damage response |
DDRNAs | DNA damage response RNAs |
decitabine; DAC | 5-Aza-2′-deoxycytidine |
DNA-PKc | DNA-dependent protein kinase |
DOX | Doxorubicin |
DPDs | Dihydropyrimidine dehydrogenases |
DSB | Double-strand break |
ECM | Extracellular matrix |
EOC | Epithelial ovarian cancer |
FBW7 | F-box and WD repeat domain-containing 7 protein |
FBX8 | F-box only protein 8 |
FDA | U.S. Food and Drug Administration |
FEN-1 | Flap structure-specific endonuclease 1 |
FGF | Fibroblast growth factor |
GSAO | 4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid |
GSH | Glutathione |
GSTs | Glutathione-S-transferases |
HER2 | Human epidermal growth factor receptor-2 gene |
hMLH1 | Human MutL homolog 1 gene |
HR | Homologous recombination |
IC50 | Half-maximum inhibitory concentration |
ICLs | Interstrand DNA cross-links |
iDNMT | DNA methylation inhibitor |
iHDAC | Histone deacetylase inhibitor |
iso-PXA | Iso-pencillixanthone A |
LQTS | Long QT syndrome |
MAPK | Mitogen-activated protein kinase |
Mcl-1 | Induced myeloid leukemia cell differentiation protein |
MDR | Multidrug resistance |
MMP | Matrix metalloproteinase |
MMR | Mismatch repair |
mPEG | Methoxypolyethylene glycol |
NER | Nucleotide excision repair |
NHEJ | Nonhomologous end joining pathway |
NSCLC | Non-small cell lung cancer |
PARP | Poly (ADP-ribose) polymerase protein |
PCNA | Lys-164-mono-ubiquitinated proliferating cell nuclear antigen |
P-gp; ABCB1 | P-glycoprotein; ATP-binding cassette subfamily B member 1 |
ROS | Reactive oxygen species |
RPA | Replication protein A |
RTK | Receptor tyrosine kinase |
SCF | SKP1-CUL1-F-box |
SCLC | Small cell lung cancer |
SNP | Single nucleotide polymorphism |
ssDNA | Single-strand DNA |
T2AA | T2 amino alcohol |
TAM | Tumor-associated macrophage |
TCGA | The Cancer Genome Atlas |
TiO2 PEG NP | Polyethylene glycol-modified titanium dioxide nanoparticle |
TLS | Translesion synthesis |
TPMTs | Thiopurine methyltransferases |
TRAIL | Tumor necrosis factor-related apoptosis-inducing ligand |
TTM | Tometodione M |
UGTs | Uridine diphospho-glucuronosyltransferases |
VCR | Vincristine |
VEGF-A | Vascular endothelial growth factor A |
γGTs | Gamma-glutamyl transferases |
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Cancer Type | miRNA | Chemotherapy Agent | Reference |
---|---|---|---|
prostate cancer | microRNA-34a | paclitaxel | [60] |
microRNA-217, microRNA-181b-5p | docetaxel, cabazitaxel | [61] | |
pancreatic cancer | microRNA-320a micro-146 | 5-FU | [62] |
microRNA-205, microRNA-7 | gemcitabine | [63] | |
colorectal cancer | microRNA-519c | 5-FU | [64] |
microRNAs-384 | oxaliplatin | [65] | |
microRNA-96 | 5-FU | [66] | |
cervical cancer | microRNA-499a | paclitaxel | [67] |
microRNA -125a | paclitaxel | [68] | |
microRNA-224 | paclitaxel | [69] | |
breast cancer | microRNA-27b-3p | tamoxifen | [70] |
microRNA-21 | trastuzumab | [71] | |
microRNA-134 | DOX | [72] | |
ovarian cancer | miR-23b | paclitaxel | [73] |
microRNA-125b | paclitaxel | [74] | |
microRNAs-449 | DOX | [75] | |
gastric cancer | microRNA-508-5p | VCR, adriamycin, cisplatin, 5-FU | [76] |
microRNA-103/107 | DOX | [77] | |
microRNA-495-3p | adriamycin, cisplatin, 5-FU, VCR | [78] |
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Bukowski, K.; Kciuk, M.; Kontek, R. Mechanisms of Multidrug Resistance in Cancer Chemotherapy. Int. J. Mol. Sci. 2020, 21, 3233. https://doi.org/10.3390/ijms21093233
Bukowski K, Kciuk M, Kontek R. Mechanisms of Multidrug Resistance in Cancer Chemotherapy. International Journal of Molecular Sciences. 2020; 21(9):3233. https://doi.org/10.3390/ijms21093233
Chicago/Turabian StyleBukowski, Karol, Mateusz Kciuk, and Renata Kontek. 2020. "Mechanisms of Multidrug Resistance in Cancer Chemotherapy" International Journal of Molecular Sciences 21, no. 9: 3233. https://doi.org/10.3390/ijms21093233
APA StyleBukowski, K., Kciuk, M., & Kontek, R. (2020). Mechanisms of Multidrug Resistance in Cancer Chemotherapy. International Journal of Molecular Sciences, 21(9), 3233. https://doi.org/10.3390/ijms21093233