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Review
. 2019 Oct 29;11(11):1677.
doi: 10.3390/cancers11111677.

Models for Understanding Resistance to Chemotherapy in Liver Cancer

Affiliations
Review

Models for Understanding Resistance to Chemotherapy in Liver Cancer

Jose J G Marin et al. Cancers (Basel). .

Abstract

The lack of response to pharmacological treatment constitutes a substantial limitation in the handling of patients with primary liver cancers (PLCs). The existence of active mechanisms of chemoresistance (MOCs) in hepatocellular carcinoma, cholangiocarcinoma, and hepatoblastoma hampers the usefulness of chemotherapy. A better understanding of MOCs is needed to develop strategies able to overcome drug refractoriness in PLCs. With this aim, several experimental models are commonly used. These include in vitro cell-free assays using subcellular systems; studies with primary cell cultures; cancer cell lines or heterologous expression systems; multicellular models, such as spheroids and organoids; and a variety of in vivo models in rodents, such as subcutaneous and orthotopic tumor xenografts or chemically or genetically induced liver carcinogenesis. Novel methods to perform programmed genomic edition and more efficient techniques to isolate circulating microvesicles offer new opportunities for establishing useful experimental tools for understanding the resistance to chemotherapy in PLCs. In the present review, using three criteria for information organization: (1) level of research; (2) type of MOC; and (3) type of PLC, we have summarized the advantages and limitations of the armamentarium available in the field of pharmacological investigation of PLC chemoresistance.

Keywords: chemoresistance; cholangiocarcinoma; hepatoblastoma; hepatocellular carcinoma; multidrug resistance; resistome.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of experimental levels and models used in the investigation of mechanisms of resistance to chemotherapy in liver cancer.

References

    1. Marin J.J.G., Briz O., Herraez E., Lozano E., Asensio M., Di Giacomo S., Romero M.R., Osorio-Padilla L.M., Santos-Llamas A.I., Serrano M.A., et al. Molecular bases of the poor response of liver cancer to chemotherapy. Clin. Res. Hepatol. Gastroenterol. 2018;42:182–192. doi: 10.1016/j.clinre.2017.12.006. - DOI - PubMed
    1. Martinez-Becerra P., Vaquero J., Romero M.R., Lozano E., Anadon C., Macias R.I., Serrano M.A., Grane-Boladeras N., Munoz-Bellvis L., Alvarez L., et al. No correlation between the expression of FXR and genes involved in multidrug resistance phenotype of primary liver tumors. Mol. Pharm. 2012;9:1693–1704. doi: 10.1021/mp300028a. - DOI - PubMed
    1. Horio M., Gottesman M.M., Pastan I. ATP-dependent transport of vinblastine in vesicles from human multidrug-resistant cells. Proc. Natl. Acad. Sci. USA. 1988;85:3580–3584. doi: 10.1073/pnas.85.10.3580. - DOI - PMC - PubMed
    1. Polli J.W., Wring S.A., Humphreys J.E., Huang L., Morgan J.B., Webster L.O., Serabjit-Singh C.S. Rational use of in vitro P-glycoprotein assays in drug discovery. J. Pharm. Exp. Ther. 2001;299:620–628. - PubMed
    1. Steck T.L., Weinstein R.S., Straus J.H., Wallach D.F. Inside-out red cell membrane vesicles: preparation and purification. Science. 1970;168:255–257. doi: 10.1126/science.168.3928.255. - DOI - PubMed

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