HR23B, a biomarker for HDAC inhibitors
<p>As our understanding of cancer biology increases and novel therapies are developed, an increasing number of predictive biomarkers are becoming clinically available. Aberrant acetylation has been strongly linked to tumourigenesis and the modulation of acetylation through targeting histone d...
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| その他の著者: | |
| フォーマット: | 学位論文 |
| 言語: | English |
| 出版事項: |
2013
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| _version_ | 1826314521715671040 |
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| author | Khan, OA |
| author2 | La Thangue, NB |
| author_facet | La Thangue, NB Khan, OA |
| author_sort | Khan, OA |
| collection | OXFORD |
| description | <p>As our understanding of cancer biology increases and novel therapies are developed, an increasing number of predictive biomarkers are becoming clinically available. Aberrant acetylation has been strongly linked to tumourigenesis and the modulation of acetylation through targeting histone deacetylase (HDAC) has led to the introduction of many HDAC inhibitors. To date, two have had regulatory approval for the treatment of cutaneous T cell lymphoma (CTCL). Modifications in chromatin control underpin the mechanism of action of HDAC inhibitors. A genome wide loss-of-function screen identified HR23B as a gene that governs sensitivity to HDAC inhibitors. HR23B shuttles ubiquitinated cargo proteins to the proteasome and elevated levels may contribute to cell death mediated by this pathway. It also governs cell sensitivity to drugs that act directly on the proteasome. HDAC inhibitors influence proteasome activity and there may be a synergistic interaction with proteasome inhibitors. HR23B and HDAC6 interact and HDAC6 may be a negative regulator of apoptosis and a positive regulator of autophagy and through its ability to down-regulate HR23B, may impact on the cellular outcome of HDAC inhibitor treatment. Expression of HR23B has been correlated with clinical response to HDAC inhibitors in a retrospective analysis of CTCL patients. The tissue expression of HR23B and the autophagy marker LC3 has been investigated and there may be a reciprocal relationship in their expression in some tumours which may provide prognostic information and patients with low HR23B expression but high levels of autophagy appear to have a particularly poor prognosis. Well designed, biomarker-driven prospective clinical trials are needed to clarify the predictive and prognostic roles of HR23B.</p> |
| first_indexed | 2024-03-07T01:59:26Z |
| format | Thesis |
| id | oxford-uuid:9cd76c0b-e70e-43f7-a92d-a99f403a077e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:33:49Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:9cd76c0b-e70e-43f7-a92d-a99f403a077e2024-09-11T11:12:25ZHR23B, a biomarker for HDAC inhibitorsThesishttp://purl.org/coar/resource_type/c_db06uuid:9cd76c0b-e70e-43f7-a92d-a99f403a077ePharmacologyTumoursClinical laboratory sciencesMedical SciencesOncologyEnglishOxford University Research Archive - Valet2013Khan, OALa Thangue, NB<p>As our understanding of cancer biology increases and novel therapies are developed, an increasing number of predictive biomarkers are becoming clinically available. Aberrant acetylation has been strongly linked to tumourigenesis and the modulation of acetylation through targeting histone deacetylase (HDAC) has led to the introduction of many HDAC inhibitors. To date, two have had regulatory approval for the treatment of cutaneous T cell lymphoma (CTCL). Modifications in chromatin control underpin the mechanism of action of HDAC inhibitors. A genome wide loss-of-function screen identified HR23B as a gene that governs sensitivity to HDAC inhibitors. HR23B shuttles ubiquitinated cargo proteins to the proteasome and elevated levels may contribute to cell death mediated by this pathway. It also governs cell sensitivity to drugs that act directly on the proteasome. HDAC inhibitors influence proteasome activity and there may be a synergistic interaction with proteasome inhibitors. HR23B and HDAC6 interact and HDAC6 may be a negative regulator of apoptosis and a positive regulator of autophagy and through its ability to down-regulate HR23B, may impact on the cellular outcome of HDAC inhibitor treatment. Expression of HR23B has been correlated with clinical response to HDAC inhibitors in a retrospective analysis of CTCL patients. The tissue expression of HR23B and the autophagy marker LC3 has been investigated and there may be a reciprocal relationship in their expression in some tumours which may provide prognostic information and patients with low HR23B expression but high levels of autophagy appear to have a particularly poor prognosis. Well designed, biomarker-driven prospective clinical trials are needed to clarify the predictive and prognostic roles of HR23B.</p> |
| spellingShingle | Pharmacology Tumours Clinical laboratory sciences Medical Sciences Oncology Khan, OA HR23B, a biomarker for HDAC inhibitors |
| title | HR23B, a biomarker for HDAC inhibitors |
| title_full | HR23B, a biomarker for HDAC inhibitors |
| title_fullStr | HR23B, a biomarker for HDAC inhibitors |
| title_full_unstemmed | HR23B, a biomarker for HDAC inhibitors |
| title_short | HR23B, a biomarker for HDAC inhibitors |
| title_sort | hr23b a biomarker for hdac inhibitors |
| topic | Pharmacology Tumours Clinical laboratory sciences Medical Sciences Oncology |
| work_keys_str_mv | AT khanoa hr23babiomarkerforhdacinhibitors |