Emerging Strategies to Overcome Chemoresistance: Structural Insights and Therapeutic Targeting of Multidrug Resistance-Linked ATP-Binding Cassette Transporters
The ATP-binding cassette (ABC) transporter superfamily, one of the largest membrane protein families, plays a crucial role in multidrug resistance (MDR) in cancer by mediating the efflux of various chemotherapeutic agents, thereby lowering their intracellular concentrations and diminishing therapeut...
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MDPI AG
2025-01-01
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| Series: | International Journal of Translational Medicine |
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| Online Access: | https://www.mdpi.com/2673-8937/5/1/6 |
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| author | Raghavendra Sashi Krishna Nagampalli Gangadhar P. Vadla Eswar Kumar Nadendla |
| author_facet | Raghavendra Sashi Krishna Nagampalli Gangadhar P. Vadla Eswar Kumar Nadendla |
| author_sort | Raghavendra Sashi Krishna Nagampalli |
| collection | DOAJ |
| description | The ATP-binding cassette (ABC) transporter superfamily, one of the largest membrane protein families, plays a crucial role in multidrug resistance (MDR) in cancer by mediating the efflux of various chemotherapeutic agents, thereby lowering their intracellular concentrations and diminishing therapeutic effectiveness. Beyond drug efflux, these transporters are also involved in vital biological processes, such as signal transduction in cancer. Over the past few decades, extensive structural and functional research has provided valuable insights into ABC transporters’ broad substrate specificity and transport mechanisms, leading to promising strategies for overcoming MDR. This review will provide a structural understanding of the interactions between ABC transporters and inhibitors to develop novel cancer therapeutics. Additionally, we focus on methods such as irradiation-based immune therapies, thermal therapies, nanomedicine, CRISPR-Cas, and natural therapies that can genetically modify ABC transporters to reduce their expression or reverse the drug efflux ability. Knowledge gained from these approaches can then be translated into the development of new cancer therapeutics that can combat chemotherapy resistance. |
| format | Article |
| id | doaj-art-e67f074aa1fc4f6d979488252444e05e |
| institution | OA Journals |
| issn | 2673-8937 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Translational Medicine |
| spelling | doaj-art-e67f074aa1fc4f6d979488252444e05e2025-08-20T01:49:00ZengMDPI AGInternational Journal of Translational Medicine2673-89372025-01-0151610.3390/ijtm5010006Emerging Strategies to Overcome Chemoresistance: Structural Insights and Therapeutic Targeting of Multidrug Resistance-Linked ATP-Binding Cassette TransportersRaghavendra Sashi Krishna Nagampalli0Gangadhar P. Vadla1Eswar Kumar Nadendla2Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Veterinary Pathobiology, Bond Life Sciences Center, 1201 Rollins Street, Columbia, MI 65211, USADepartment of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USAThe ATP-binding cassette (ABC) transporter superfamily, one of the largest membrane protein families, plays a crucial role in multidrug resistance (MDR) in cancer by mediating the efflux of various chemotherapeutic agents, thereby lowering their intracellular concentrations and diminishing therapeutic effectiveness. Beyond drug efflux, these transporters are also involved in vital biological processes, such as signal transduction in cancer. Over the past few decades, extensive structural and functional research has provided valuable insights into ABC transporters’ broad substrate specificity and transport mechanisms, leading to promising strategies for overcoming MDR. This review will provide a structural understanding of the interactions between ABC transporters and inhibitors to develop novel cancer therapeutics. Additionally, we focus on methods such as irradiation-based immune therapies, thermal therapies, nanomedicine, CRISPR-Cas, and natural therapies that can genetically modify ABC transporters to reduce their expression or reverse the drug efflux ability. Knowledge gained from these approaches can then be translated into the development of new cancer therapeutics that can combat chemotherapy resistance.https://www.mdpi.com/2673-8937/5/1/6ABC transportersmultidrug resistance (MDR)ABC transporter inhibitorscancer therapeuticsdrug efflux mechanism |
| spellingShingle | Raghavendra Sashi Krishna Nagampalli Gangadhar P. Vadla Eswar Kumar Nadendla Emerging Strategies to Overcome Chemoresistance: Structural Insights and Therapeutic Targeting of Multidrug Resistance-Linked ATP-Binding Cassette Transporters International Journal of Translational Medicine ABC transporters multidrug resistance (MDR) ABC transporter inhibitors cancer therapeutics drug efflux mechanism |
| title | Emerging Strategies to Overcome Chemoresistance: Structural Insights and Therapeutic Targeting of Multidrug Resistance-Linked ATP-Binding Cassette Transporters |
| title_full | Emerging Strategies to Overcome Chemoresistance: Structural Insights and Therapeutic Targeting of Multidrug Resistance-Linked ATP-Binding Cassette Transporters |
| title_fullStr | Emerging Strategies to Overcome Chemoresistance: Structural Insights and Therapeutic Targeting of Multidrug Resistance-Linked ATP-Binding Cassette Transporters |
| title_full_unstemmed | Emerging Strategies to Overcome Chemoresistance: Structural Insights and Therapeutic Targeting of Multidrug Resistance-Linked ATP-Binding Cassette Transporters |
| title_short | Emerging Strategies to Overcome Chemoresistance: Structural Insights and Therapeutic Targeting of Multidrug Resistance-Linked ATP-Binding Cassette Transporters |
| title_sort | emerging strategies to overcome chemoresistance structural insights and therapeutic targeting of multidrug resistance linked atp binding cassette transporters |
| topic | ABC transporters multidrug resistance (MDR) ABC transporter inhibitors cancer therapeutics drug efflux mechanism |
| url | https://www.mdpi.com/2673-8937/5/1/6 |
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