Antibody-Drug Conjugates and Targeted Treatment Strategies for Hepatocellular Carcinoma: A Drug-Delivery Perspective
Increased understanding of cancer biology, pharmacology and drug delivery has provided a new framework for drug discovery and product development that relies on the unique expression of specific macromolecules (i.e., antigens) on the surface of tumour cells. This has enabled the development of anti-...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/12/2861 |
| _version_ | 1797564591958392832 |
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| author | David Dahlgren Hans Lennernäs |
| author_facet | David Dahlgren Hans Lennernäs |
| author_sort | David Dahlgren |
| collection | DOAJ |
| description | Increased understanding of cancer biology, pharmacology and drug delivery has provided a new framework for drug discovery and product development that relies on the unique expression of specific macromolecules (i.e., antigens) on the surface of tumour cells. This has enabled the development of anti-cancer treatments that combine the selectivity of antibodies with the efficacy of highly potent chemotherapeutic small molecules, called antibody-drug conjugates (ADCs). ADCs are composed of a cytotoxic drug covalently linked to an antibody which then selectively binds to a highly expressed antigen on a cancer cell; the conjugate is then internalized by the cell where it releases the potent cytotoxic drug and efficiently kills the tumour cell. There are, however, many challenges in the development of ADCs, mainly around optimizing the therapeutic/safety benefits. These challenges are discussed in this review; they include issues with the plasma stability and half-life of the ADC, its transport from blood into and distribution throughout the tumour compartment, cancer cell antigen expression and the ADC binding affinity to the target antigen, the cell internalization process, cleaving of the cytotoxic drug from the ADC, and the cytotoxic effect of the drug on the target cells. Finally, we present a summary of some of the experimental ADC strategies used in the treatment of hepatocellular carcinoma, from the recent literature. |
| first_indexed | 2024-03-10T18:59:15Z |
| format | Article |
| id | doaj.art-6ab175bc4b4a449dba046528ccd44756 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T18:59:15Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-6ab175bc4b4a449dba046528ccd447562023-11-20T04:30:47ZengMDPI AGMolecules1420-30492020-06-012512286110.3390/molecules25122861Antibody-Drug Conjugates and Targeted Treatment Strategies for Hepatocellular Carcinoma: A Drug-Delivery PerspectiveDavid Dahlgren0Hans Lennernäs1Department of Pharmacy, Division of Biopharmaceutics, Uppsala University, 752 36 Uppsala, SwedenDepartment of Pharmacy, Division of Biopharmaceutics, Uppsala University, 752 36 Uppsala, SwedenIncreased understanding of cancer biology, pharmacology and drug delivery has provided a new framework for drug discovery and product development that relies on the unique expression of specific macromolecules (i.e., antigens) on the surface of tumour cells. This has enabled the development of anti-cancer treatments that combine the selectivity of antibodies with the efficacy of highly potent chemotherapeutic small molecules, called antibody-drug conjugates (ADCs). ADCs are composed of a cytotoxic drug covalently linked to an antibody which then selectively binds to a highly expressed antigen on a cancer cell; the conjugate is then internalized by the cell where it releases the potent cytotoxic drug and efficiently kills the tumour cell. There are, however, many challenges in the development of ADCs, mainly around optimizing the therapeutic/safety benefits. These challenges are discussed in this review; they include issues with the plasma stability and half-life of the ADC, its transport from blood into and distribution throughout the tumour compartment, cancer cell antigen expression and the ADC binding affinity to the target antigen, the cell internalization process, cleaving of the cytotoxic drug from the ADC, and the cytotoxic effect of the drug on the target cells. Finally, we present a summary of some of the experimental ADC strategies used in the treatment of hepatocellular carcinoma, from the recent literature.https://www.mdpi.com/1420-3049/25/12/2861antibody-drug conjugateshepatocellular carcinomaliver cancerdrug discoverymonoclonal antibodiesbioconjugation |
| spellingShingle | David Dahlgren Hans Lennernäs Antibody-Drug Conjugates and Targeted Treatment Strategies for Hepatocellular Carcinoma: A Drug-Delivery Perspective Molecules antibody-drug conjugates hepatocellular carcinoma liver cancer drug discovery monoclonal antibodies bioconjugation |
| title | Antibody-Drug Conjugates and Targeted Treatment Strategies for Hepatocellular Carcinoma: A Drug-Delivery Perspective |
| title_full | Antibody-Drug Conjugates and Targeted Treatment Strategies for Hepatocellular Carcinoma: A Drug-Delivery Perspective |
| title_fullStr | Antibody-Drug Conjugates and Targeted Treatment Strategies for Hepatocellular Carcinoma: A Drug-Delivery Perspective |
| title_full_unstemmed | Antibody-Drug Conjugates and Targeted Treatment Strategies for Hepatocellular Carcinoma: A Drug-Delivery Perspective |
| title_short | Antibody-Drug Conjugates and Targeted Treatment Strategies for Hepatocellular Carcinoma: A Drug-Delivery Perspective |
| title_sort | antibody drug conjugates and targeted treatment strategies for hepatocellular carcinoma a drug delivery perspective |
| topic | antibody-drug conjugates hepatocellular carcinoma liver cancer drug discovery monoclonal antibodies bioconjugation |
| url | https://www.mdpi.com/1420-3049/25/12/2861 |
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