DOI: 10.1634/theoncologist.8-5-411. The Role of ABC Transporters in Clinical Practice

The Role of ABC Transporters in Clinical Practice

10.1634/theoncologist.8-5-411

Crossref journal-article

Oxford University Press (OUP)

The Oncologist (286)

Abstract

Abstract Learning Objectives After completing this course, the reader will be able to: Discuss the function of ABC transporters. Outline the levels of expression of MDR in tumors. Determine the role of P-gp inhibitors in clinical practice. Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com Drug resistance remains one of the primary causes of suboptimal outcomes in cancer therapy. ATP-binding cassette (ABC) transporters are a family of transporter proteins that contribute to drug resistance via ATP-dependent drug efflux pumps. P-glycoprotein (P-gp), encoded by the MDR1 gene, is an ABC transporter normally involved in the excretion of toxins from cells. It also confers resistance to certain chemotherapeutic agents. P-gp is overexpressed at baseline in chemotherapy-resistant tumors, such as colon and kidney cancers, and is upregulated after disease progression following chemotherapy in malignancies such as leukemia and breast cancer. Other transporter proteins mediating drug resistance include those in the multidrug-resistance-associated protein (MRP) family, notably MRP1, and ABCG2. These transporters are also involved in normal physiologic functions. The expressions of MRP family members and ABCG2 have not been well worked out in cancer. Increased drug accumulation and drug resistance reversal with P-gp inhibitors have been well documented in vitro, but only suggested in clinical trials. Limitations in the design of early resistance reversal trials contributed to disappointing results. Despite this, three randomized trials have shown statistically significant benefits with the use of a P-gp inhibitor in combination with chemotherapy. Improved diagnostic techniques aimed at the selection of patients with tumors that express P-gp should result in more successful outcomes. Further optimism is warranted with the advent of potent, nontoxic inhibitors and new treatment strategies, including the combination of new targeted therapies with therapies aimed at the prevention of drug resistance.

Bibliography

Leonard, G. D., Fojo, T., & Bates, S. E. (2003). The Role of ABC Transporters in Clinical Practice. The Oncologist, 8(5), 411â424.

Authors 3

Gregory D. Leonard (first)
Tito Fojo (additional)
Susan E. Bates (additional)

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Dates

Type	When
Created	21 years ago (Aug. 24, 2004, 5:38 p.m.)
Deposited	3 years, 8 months ago (Dec. 22, 2021, 11:41 a.m.)
Indexed	4 days, 12 hours ago (Sept. 3, 2025, 6:59 a.m.)
Issued	21 years, 11 months ago (Oct. 1, 2003)
Published	21 years, 11 months ago (Oct. 1, 2003)
Published Online	21 years, 11 months ago (Oct. 1, 2003)
Published Print	21 years, 11 months ago (Oct. 1, 2003)

Funders 0

None

BibTeX

@article{Leonard_2003, title={The Role of ABC Transporters in Clinical Practice}, volume={8}, ISSN={1549-490X}, url={http://dx.doi.org/10.1634/theoncologist.8-5-411}, DOI={10.1634/theoncologist.8-5-411}, number={5}, journal={The Oncologist}, publisher={Oxford University Press (OUP)}, author={Leonard, Gregory D. and Fojo, Tito and Bates, Susan E.}, year={2003}, month=oct, pages={411–424} }

JSON

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  "abstract": "<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Learning Objectives</jats:title>\n                  <jats:p>After completing this course, the reader will be able to:</jats:p>\n                  <jats:p>Discuss the function of ABC transporters. Outline the levels of expression of MDR in tumors. Determine the role of P-gp inhibitors in clinical practice.</jats:p>\n                  <jats:p>Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com</jats:p>\n                  <jats:p>Drug resistance remains one of the primary causes of suboptimal outcomes in cancer therapy. ATP-binding cassette (ABC) transporters are a family of transporter proteins that contribute to drug resistance via ATP-dependent drug efflux pumps. P-glycoprotein (P-gp), encoded by the MDR1 gene, is an ABC transporter normally involved in the excretion of toxins from cells. It also confers resistance to certain chemotherapeutic agents. P-gp is overexpressed at baseline in chemotherapy-resistant tumors, such as colon and kidney cancers, and is upregulated after disease progression following chemotherapy in malignancies such as leukemia and breast cancer. Other transporter proteins mediating drug resistance include those in the multidrug-resistance-associated protein (MRP) family, notably MRP1, and ABCG2. These transporters are also involved in normal physiologic functions. The expressions of MRP family members and ABCG2 have not been well worked out in cancer.</jats:p>\n                  <jats:p>Increased drug accumulation and drug resistance reversal with P-gp inhibitors have been well documented in vitro, but only suggested in clinical trials. Limitations in the design of early resistance reversal trials contributed to disappointing results. Despite this, three randomized trials have shown statistically significant benefits with the use of a P-gp inhibitor in combination with chemotherapy. Improved diagnostic techniques aimed at the selection of patients with tumors that express P-gp should result in more successful outcomes. Further optimism is warranted with the advent of potent, nontoxic inhibitors and new treatment strategies, including the combination of new targeted therapies with therapies aimed at the prevention of drug resistance.</jats:p>\n               </jats:sec>",
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