Role of ATP-Binding Cassette Transporter Proteins in CNS Tumors: Resistance- Based Perspectives and Clinical Updates

Author(s): M. Asif, M. Usman, Shahid Ayub, Sahar Farhat, Zilli Huma, Jawad Ahmed, Mohammad Amjad Kamal, Deema Hussein, Aneela Javed*, Ishaq Khan*

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 37 , 2020

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Abstract:

Despite gigantic advances in medical research and development, chemotherapeutic resistance remains a major challenge in complete remission of CNS tumors. The failure of complete eradication of CNS tumors has been correlated with the existence of several factors including overexpression of transporter proteins. To date, 49 ABC-transporter proteins (ABC-TPs) have been reported in humans, and the evidence of their strong association with chemotherapeutics’ influx, dissemination, and efflux in CNS tumors, is growing. Research studies on CNS tumors are implicating ABC-TPs as diagnostic, prognostic and therapeutic biomarkers that may be utilised in preclinical and clinical studies. With the current advancements in cell biology, molecular analysis of genomic and transcriptomic interplay, and protein homology-based drug-transporters interaction, our research approaches are streamlining the roles of ABC-TPs in cancer and multidrug resistance. Potential inhibitors of ABC-TP for better clinical outcomes in CNS tumors have emerged. Elacridar has shown to enhance the chemo-sensitivity of Dasatanib and Imatinib in various glioma models. Tariquidar has improved the effectiveness of Temozolomide’s in CNS tumors. Although these inhibitors have been effective in preclinical settings, their clinical outcomes have not been as significant in clinical trials. Thus, to have a better understanding of the molecular evaluations of ABC-TPs, as well as drug-interactions, further research is being pursued in research labs. Our lab aims to better comprehend the biological mechanisms involved in drug resistance and to explore novel strategies to increase the clinical effectiveness of anticancer chemotherapeutics, which will ultimately improve clinical outcomes.

Keywords: CNS tumors, multidrug resistance, ABC transporters, ABCB1, ABCG2, ABCC1, ABCC3, inhibitors, Elacridar, Tariquidar, clinical trials.

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Article Details

VOLUME: 26
ISSUE: 37
Year: 2020
Page: [4748 - 4764]
Pages: 17
DOI: 10.2174/1381612826666200224112141
Price: $95

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