Glutathione Transferase P1: Potential Therapeutic Target in Ovarian Cancer
Chemotherapy resistance of ovarian cancer, regarded as the most lethal malignant gynecological disease, can be explained by several mechanisms, including increased activity of efflux transporters leading to decreased intracellular drug accumulation, increased efflux of the therapeutic agents from th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/58/11/1660 |
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| author | Petar Simic Igor Pljesa Lazar Nejkovic Djurdja Jerotic Vesna Coric Jelena Stulic Nenad Kokosar Dunja Popov Ana Savic-Radojevic Vladimir Pazin Marija Pljesa-Ercegovac |
| author_facet | Petar Simic Igor Pljesa Lazar Nejkovic Djurdja Jerotic Vesna Coric Jelena Stulic Nenad Kokosar Dunja Popov Ana Savic-Radojevic Vladimir Pazin Marija Pljesa-Ercegovac |
| author_sort | Petar Simic |
| collection | DOAJ |
| description | Chemotherapy resistance of ovarian cancer, regarded as the most lethal malignant gynecological disease, can be explained by several mechanisms, including increased activity of efflux transporters leading to decreased intracellular drug accumulation, increased efflux of the therapeutic agents from the cell by multidrug-resistance-associated protein (MRP1), enhanced DNA repair, altered apoptotic pathways, silencing of a number of genes, as well as drug inactivation, especially by glutathione transferase P1 (GSTP1). Indeed, GSTP1 has been recognized as the major enzyme responsible for the conversion of drugs most commonly used to treat metastatic ovarian cancer into less effective forms. Furthermore, GSTP1 may even be responsible for chemoresistance of non-GST substrate drugs by mechanisms such as interaction with efflux transporters or different signaling molecules involved in regulation of apoptosis. Recently, microRNAs (miRNAs) have been identified as important gene regulators in ovarian cancer, which are able to target GST-mediated drug metabolism in order to regulate drug resistance. So far, miR-186 and miR-133b have been associated with reduced ovarian cancer drug resistance by silencing the expression of the drug-resistance-related proteins, GSTP1 and MDR1. Unfortunately, sometimes miRNAs might even enhance the drug resistance in ovarian cancer, as shown for miR-130b. Therefore, chemoresistance in ovarian cancer treatment represents a very complex process, but strategies that influence GSTP1 expression in ovarian cancer as a therapeutic target, as well as miRNAs affecting GSTP1 expression, seem to represent promising predictors of chemotherapeutic response in ovarian cancer, while at the same time represent potential targets to overcome chemoresistance in the future. |
| first_indexed | 2024-03-09T18:10:15Z |
| format | Article |
| id | doaj.art-c72ecbf5c3364e8ba26b2af044964511 |
| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-09T18:10:15Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicina |
| spelling | doaj.art-c72ecbf5c3364e8ba26b2af0449645112023-11-24T09:11:33ZengMDPI AGMedicina1010-660X1648-91442022-11-015811166010.3390/medicina58111660Glutathione Transferase P1: Potential Therapeutic Target in Ovarian CancerPetar Simic0Igor Pljesa1Lazar Nejkovic2Djurdja Jerotic3Vesna Coric4Jelena Stulic5Nenad Kokosar6Dunja Popov7Ana Savic-Radojevic8Vladimir Pazin9Marija Pljesa-Ercegovac10Obstetrics and Gynaecology Clinic Narodni Front, 11000 Belgrade, SerbiaGynaecology and Obstetrics Centre Dr Dragiša Mišović, 11000 Belgrade, SerbiaObstetrics and Gynaecology Clinic Narodni Front, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaObstetrics and Gynaecology Clinic Narodni Front, 11000 Belgrade, SerbiaObstetrics and Gynaecology Clinic Narodni Front, 11000 Belgrade, SerbiaObstetrics and Gynaecology Clinic Narodni Front, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaObstetrics and Gynaecology Clinic Narodni Front, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaChemotherapy resistance of ovarian cancer, regarded as the most lethal malignant gynecological disease, can be explained by several mechanisms, including increased activity of efflux transporters leading to decreased intracellular drug accumulation, increased efflux of the therapeutic agents from the cell by multidrug-resistance-associated protein (MRP1), enhanced DNA repair, altered apoptotic pathways, silencing of a number of genes, as well as drug inactivation, especially by glutathione transferase P1 (GSTP1). Indeed, GSTP1 has been recognized as the major enzyme responsible for the conversion of drugs most commonly used to treat metastatic ovarian cancer into less effective forms. Furthermore, GSTP1 may even be responsible for chemoresistance of non-GST substrate drugs by mechanisms such as interaction with efflux transporters or different signaling molecules involved in regulation of apoptosis. Recently, microRNAs (miRNAs) have been identified as important gene regulators in ovarian cancer, which are able to target GST-mediated drug metabolism in order to regulate drug resistance. So far, miR-186 and miR-133b have been associated with reduced ovarian cancer drug resistance by silencing the expression of the drug-resistance-related proteins, GSTP1 and MDR1. Unfortunately, sometimes miRNAs might even enhance the drug resistance in ovarian cancer, as shown for miR-130b. Therefore, chemoresistance in ovarian cancer treatment represents a very complex process, but strategies that influence GSTP1 expression in ovarian cancer as a therapeutic target, as well as miRNAs affecting GSTP1 expression, seem to represent promising predictors of chemotherapeutic response in ovarian cancer, while at the same time represent potential targets to overcome chemoresistance in the future.https://www.mdpi.com/1648-9144/58/11/1660ovarian cancerchemoresistanceglutathione S transferase P1microRNAapoptosis |
| spellingShingle | Petar Simic Igor Pljesa Lazar Nejkovic Djurdja Jerotic Vesna Coric Jelena Stulic Nenad Kokosar Dunja Popov Ana Savic-Radojevic Vladimir Pazin Marija Pljesa-Ercegovac Glutathione Transferase P1: Potential Therapeutic Target in Ovarian Cancer Medicina ovarian cancer chemoresistance glutathione S transferase P1 microRNA apoptosis |
| title | Glutathione Transferase P1: Potential Therapeutic Target in Ovarian Cancer |
| title_full | Glutathione Transferase P1: Potential Therapeutic Target in Ovarian Cancer |
| title_fullStr | Glutathione Transferase P1: Potential Therapeutic Target in Ovarian Cancer |
| title_full_unstemmed | Glutathione Transferase P1: Potential Therapeutic Target in Ovarian Cancer |
| title_short | Glutathione Transferase P1: Potential Therapeutic Target in Ovarian Cancer |
| title_sort | glutathione transferase p1 potential therapeutic target in ovarian cancer |
| topic | ovarian cancer chemoresistance glutathione S transferase P1 microRNA apoptosis |
| url | https://www.mdpi.com/1648-9144/58/11/1660 |
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