The contribution of copper efflux transporters ATP7A and ATP7B to chemoresistance and personalized medicine in ovarian cancer

Lukanovič, David (author), Herzog, Maruša (author), Kobal, Borut (author), Černe, Katarina (author)

Ovarian cancer has the highest mortality rate among all gynecologic cancers, with most patients presenting with advanced stage tumors. About a third of patients do not respond to primary platinum-based chemotherapy treatment, and over time up to 80 % of others develop chemoresistance, rendering recurrent disease incurable. Moreover, according to latest EMSO-ESGO (European Society for Medical Oncology - European Society for Gynecological Oncology) consensus conference manuscript on ovarian cancer, there are currently no validated molecular predictive biomarkers for platinum resistance. Recent studies suggest that the copper efflux transporters ATP7A and ATP7B play an important role in platinum resistance. In addition, by exploring their role in mediating resistance, new pathways of platinum resistance emerge, such as lysosomal storage disorders, which might be explored in the future as a new target to circumvent platinum resistance. This review outlines a challenging clinical hurdle in ovarian cancer therapy due to platinum resistance, links between the essential trace element copper and cytotoxic platinum-based medicines, and enigmatic mechanisms of ATP7A and ATP7B mediating platinum resistance. It then presents clinical studies showing a significant association of ATP7A and ATP7B with response to cisplatin/carboplatin and prognosis. Based on the results of in vitro assays, disease-relevant animal models, and clinical studies to date, it may be concluded that APT7A and ATP7B deserve further development as predictive markers of platinum resistance in ovarian cancer. Both transporters could play a particularly important role in early estimation of therapy response to identify platinum-resistant tumors and to adjust the treatment of ovarian cancer patients accordingly.

• Language: English
• Keywords: gyneacology, ovarian cancer, chemoresistance, predictive marker, ATP7A, ATP7B
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 12 str.
• Numbering: Vol. 129, art. 110401
• PID: 20.500.12556/RUL-128791
• UDC: 618.1
• ISSN on article: 1950-6007
• DOI: 10.1016/j.biopha.2020.110401
• COBISS.SI-ID: 21068547
• Publication date in RUL: 29.07.2021

Record is a part of a journal

• Title: Biomedicine & pharmacotherapy
• Publisher: Elsevier
• ISSN: 1950-6007
• COBISS.SI-ID: 23136261

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: ginekologija, rak jajčnika, kemoresistenca, ATP7A, ATP7B

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0067
• Name: Farmakologija in farmakogenomika

• Funder: Other - Other funder or multiple funders
• Funding programme: Ljubljana University Medical Center
• Project number: 20180033
• Name: Transport proteins as biomarkers for selecting the optimal time for cytoreductive surgery in cancer