Pascale, Rosa M. and Joseph, Christy and Latte, Gavinella and Evert, Matthias and Feo, Francesco and Calvisi, Diego F. (2016) DNA-PKcs: A promising therapeutic target in human hepatocellular carcinoma? DNA REPAIR, 47. pp. 12-20. ISSN 1568-7864, 1568-7856
Full text not available from this repository. (Request a copy)Abstract
Hepatocellular carcinoma (HCC) is a frequent and deadly disease worldwide. The absence of effective therapies when the tumor is surgically unresectable leads to an extremely poor outcome of HCC patients. Thus, it is mandatory to elucidate the molecular pathogenesis of HCC in order to develop novel therapeutic strategies against this pernicious tumor. Mounting evidence indicates that suppression of the DNA damage response machinery might be deleterious for the survival and growth of the tumor cells. In particular, DNA dependent protein kinase catalytic subunit (DNA-PKcs), a major player in the non-homologous end joining (NHEJ) repair process, seems to represent a valuable target for innovative anti-neoplastic therapies in cancer. DNA-PKcs levels are strongly upregulated and associated with a poor clinical outcome in various tumor types, including HCC. Importantly, DNA-PKcs not only protects tumor cells from harmful DNA insults coming either from the microenvironment or chemotherapeutic drug treatments, but also possesses additional properties, independent from its DNA repair activity, that provide growth advantages to cancer cells. These properties (metabolic and gene reprogramming, invasiveness and metastasis, resistance to apoptosis, etc.) have started to be elucidated. In the present review, we summarize the physiologic and oncogenic roles of DNA-PKcs, with a special emphasis on liver cancer. In particular, this work focuses on the molecular mechanism whereby DNA-PKcs exerts its pro-tumorigenic activity in cancer cells. In addition, the upstream regulator of DNA-PKcs activation as well as its downstream effectors thus far identified are illustrated. Furthermore, the potential therapeutic strategies aimed at inhibiting DNA-PKcs activity in HCC are discussed. (C) 2016 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DEPENDENT PROTEIN-KINASE; STRAND BREAK REPAIR; ESTROGEN-RECEPTOR-ALPHA; CATALYTIC SUBUNIT; SIGNALING PATHWAYS; TRANSCRIPTIONAL REGULATION; STRUCTURAL MODEL; GENE-EXPRESSION; CANCER; END; Hepatocellular carcinoma; DNA repair; Signaling pathways; Targeted therapies |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Petra Gürster |
| Date Deposited: | 27 Aug 2020 07:48 |
| Last Modified: | 27 Aug 2020 07:48 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4005 |
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