Abstract
In oncology new therapeutic strategies are needed to increase efficacy and reduce side effects. For her thesis, Valerie R. Wiersma studied the anticancer activity of the human proteins TRAIL and galectin-9. TRAIL is a protein that immune cells (e.g. T-cells) use to prevent and fight cancer by selectively inducing programmed cell death (apoptosis) in malignant cells. Unfortunately, cancer cells develop various ways to resist or counteract the anticancer activity of immune cells. Therefore, new recombinant fusion proteins were designed to act as drugs that promote and/or reactivate anticancer immune responses. For this purpose, TRAIL was genetically fused to an antibody fragment with immune-activating properties. In this way, various types of immune effector cells could be activated and simultaneously armed with TRAIL, which significantly enhanced their anticancer activity.
It is well-known that cancer cells develop resistance to commonly used anticancer drugs as a result of mutations in cell death signaling pathways or in metabolic processes that promote cancer cell survival. Wiersma uncovered that galectin-9 can be used to induce cell death in cancer cells. The mode-of-action of galectin-9 involved the selective inhibition of autophagy, a catabolic process that cancer cells misuse to gain resistance towards conventional anticancer drugs. This discovery suggests that galectin-9 may be of use to overcome therapy resistance in cancer cells.
Further research is ongoing to evaluate the suitability of TRAIL fusion proteins and galectin-9 for future clinical use in cancer patients.
It is well-known that cancer cells develop resistance to commonly used anticancer drugs as a result of mutations in cell death signaling pathways or in metabolic processes that promote cancer cell survival. Wiersma uncovered that galectin-9 can be used to induce cell death in cancer cells. The mode-of-action of galectin-9 involved the selective inhibition of autophagy, a catabolic process that cancer cells misuse to gain resistance towards conventional anticancer drugs. This discovery suggests that galectin-9 may be of use to overcome therapy resistance in cancer cells.
Further research is ongoing to evaluate the suitability of TRAIL fusion proteins and galectin-9 for future clinical use in cancer patients.
| Original language | English |
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| Qualification | Doctor of Philosophy |
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| Award date | 10-May-2017 |
| Place of Publication | [Groningen] |
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| Print ISBNs | 978-90-367-9768-9 |
| Electronic ISBNs | 978-90-367-9767-2 |
| Publication status | Published - 2017 |