SLC7A8 coding for LAT2 is associated with early disease progression in osteosarcoma and transports doxorubicin

SLC7A8 coding for LAT2 is associated with early disease progression in osteosarcoma and transports doxorubicin

Background: Despite (neo) adjuvant chemotherapy with cisplatin, doxorubicin and methotrexate, some patients with primary osteosarcoma progress during first-line systemic treatment and have a poor prognosis. In this study, we investigated whether patients with early disease progression (EDP), are cha...

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Veröffentlicht in:Frontiers in pharmacology 2022-11, Vol.13, p.1042989-1042989
Hauptverfasser: Hurkmans, Evelien G. E., Koenderink, Jan B., van den Heuvel, Jeroen J. M. W., Versleijen-Jonkers, Yvonne M. H., Hillebrandt-Roeffen, Melissa H. S., Groothuismink, Johanne M., Vos, Hanneke I., van der Graaf, Winette T. A., Flucke, Uta, Muradjan, Grigor, Schreuder, Hendrik W. B., Hagleitner, Melanie M., Brunner, Han G., Gelderblom, Hans, Cleton-Jansen, Anne-Marie, Guchelaar, Henk-Jan, de Bont, Eveline S. J. M., Touw, Daan J., Nijhoff, G. Jan, Kremer, Leontien C. M., Caron, Huib, Windsor, Rachael, Patiño-García, Ana, González-Neira, Anna, Saletta, Federica, McCowage, Geoff, Nagabushan, Sumanth, Catchpoole, Daniel, te Loo, D. Maroeska W. M., Coenen, Marieke J. H.
Format: Artikel
Sprache:eng
Schlagworte:
doxorubicin
early disease progression
L-type amino acid transporter 2
osteosarcoma
pharmacogenetics
Pharmacology
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Zusammenfassung:Background: Despite (neo) adjuvant chemotherapy with cisplatin, doxorubicin and methotrexate, some patients with primary osteosarcoma progress during first-line systemic treatment and have a poor prognosis. In this study, we investigated whether patients with early disease progression (EDP), are characterized by a distinctive pharmacogenetic profile. Methods and Findings: Germline DNA from 287 Dutch high-grade osteosarcoma patients was genotyped using the DMET Plus array (containing 1,936 genetic markers in 231 drug metabolism and transporter genes). Associations between genetic variants and EDP were assessed using logistic regression models and associated variants ( p
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2022.1042989