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

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

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.

• Jezik: Angleški jezik
• Ključne besede: gyneacology, ovarian cancer, chemoresistance, predictive marker, ATP7A, ATP7B
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.02 - Pregledni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2020
• Št. strani: 12 str.
• Številčenje: Vol. 129, art. 110401
• PID: 20.500.12556/RUL-128791
• UDK: 618.1
• ISSN pri članku: 1950-6007
• DOI: 10.1016/j.biopha.2020.110401
• COBISS.SI-ID: 21068547
• Datum objave v RUL: 29.07.2021

Gradivo je del revije

• Naslov: Biomedicine & pharmacotherapy
• Založnik: Elsevier
• ISSN: 1950-6007
• COBISS.SI-ID: 23136261

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: ginekologija, rak jajčnika, kemoresistenca, ATP7A, ATP7B

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P3-0067
• Naslov: Farmakologija in farmakogenomika

• Financer: Drugi - Drug financer ali več financerjev
• Program financ.: Ljubljana University Medical Center
• Številka projekta: 20180033
• Naslov: Transport proteins as biomarkers for selecting the optimal time for cytoreductive surgery in cancer