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Review
. 2019 Mar 22;11(3):407.
doi: 10.3390/cancers11030407.

Mechanisms of Anticancer Drug Resistance in Hepatoblastoma

Jose J G Marin  1   2 , Candela Cives-Losada  3 , Maitane Asensio  4 , Elisa Lozano  5   6 , Oscar Briz  7   8 , Rocio I R Macias  9   10
Affiliations
Review

Mechanisms of Anticancer Drug Resistance in Hepatoblastoma

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

Abstract

The most frequent liver tumor in children is hepatoblastoma (HB), which derives from embryonic parenchymal liver cells or hepatoblasts. Hepatocellular carcinoma (HCC), which rarely affects young people, causes one fourth of deaths due to cancer in adults. In contrast, HB usually has better prognosis, but this is still poor in 20% of cases. Although more responsive to chemotherapy than HCC, the failure of pharmacological treatment used before and/or after surgical resection is an important limitation in the management of patients with HB. To advance in the implementation of personalized medicine it is important to select the best combination among available anti-HB drugs, such as platinum derivatives, anthracyclines, etoposide, tyrosine-kinase inhibitors, Vinca alkaloids, 5-fluorouracil, monoclonal antibodies, irinotecan and nitrogen mustards. This requires predicting the sensitivity to these drugs of each tumor at each time because, it should be kept in mind, that cancer chemoresistance is a dynamic process of Darwinian nature. For this goal it is necessary to improve our understanding of the mechanisms of chemoresistance involved in the refractoriness of HB against the pharmacological challenge and how they evolve during treatment. In this review we have summarized the current knowledge on the multifactorial and complex factors responsible for the lack of response of HB to chemotherapy.

Keywords: chemoresistance; chemotherapy; liver cancer; pediatric cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of mechanisms involved in chemoresistance (MOC) of hepatoblastoma to platinum derivatives. The table indicates the change in hepatoblastoma of the expression levels of genes involved in the chemoresistance to platinum derivatives: uptake transporters (MOC-1A), export pumps (MOC-1B), detoxifying enzymes (MOC-2), DNA repair enzymes (MOC-4), pro-apoptotic proteins (MOC-5A), anti-apoptotic proteins (MOC-5B), tumor cell microenvironment (MOC-6) and epithelial-mesenchymal transition (EMT) (MOC-7).
Figure 2
Figure 2
Schematic representation of mechanisms involved in chemoresistance (MOC) of hepatoblastoma to anthracyclines. The table indicates the change in hepatoblastoma of the expression levels of genes involved in the chemoresistance to anthracyclines: uptake transporters (MOC-1A), export pumps (MOC-1B), detoxifying enzymes (MOC-2), molecular targets (MOC-3), DNA repair enzymes (MOC-4), pro-apoptotic proteins (MOC-5A) and anti-apoptotic proteins (MOC-5B). TOPO, topoisomerase.
See this image and copyright information in PMC

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