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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2013.1
- 수록면
- 251 - 262 (12page)
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Arginine deprivation is a novel antimetabolite strategy for the treatment of argininedependent cancers that exploits differential expression and regulation of key urea cycle enzymes. Several studies have focused on inactivation of argininosuccinate synthetase 1 (ASS1) in a range of malignancies, including melanoma, hepatocellular carcinoma (HCC), mesothelial and urological cancers, sarcomas, and lymphomas.
Epigenetic silencing has been identified as a key mechanism for loss of the tumor suppressor role of ASS1 leading to tumoral dependence on exogenous arginine. More recently, dysregulation of argininosuccinate lyase has been documented in a subset of arginine auxotrophic glioblastoma multiforme, HCC and in fumarate hydratasemutant renal cancers. Clinical trials of several arginine depletors are ongoing, including pegylated arginine deiminase (ADI-PEG20, Polaris Group) and bioengineered forms of human arginase. ADI-PEG20 is furthest along the path of clinical development from combinatorial phase 1 to phase 3 trials and is described in more detail.
The challenge will be to identify tumors sensitive to drugs such as ADI-PEG20 and integrate these agents into multimodality drug regimens using imaging and tissue/fluid-based biomarkers as predictors of response. Lastly, resistance pathways to arginine deprivation require further study to optimize arginine-targeted therapies in the oncology clinic.
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참고문헌 (106)
참고문헌 신청
Braas D / 2012 / Metabolomics strategy reveals subpopulation of liposarcomas sensitive to gemcitabine treatment / Cancer Discov 2:1109~1117
Van Tine BA / 2013 / Using pegylated arginine deiminase (ADI-PEG20) for the treatment of sarcomas that lack argininosuccinate synthesase 1 expression / J Clin Oncol 31(S):10526
Lan J / 2013 / Deficiency in expression and epigenetic DNA methylation of ASS1 gene in nasopharyngeal carcinoma: negative prognostic impact and therapeutic relevance / Tumour Biol 30
Possemato R / 2011 / Functional genomics reveal that the serine synthesis pathway is essential in breast cancer / Nature 476:346~350
Erez A / 2011 / Requirement of argininosuccinate lyase for systemic nitric oxide production / Nat Med 17:1619~1626
Van Tine BA / 2013 / Using pegylated arginine deiminase (ADI-PEG20) for the treatment of sarcomas that lack argininosuccinate synthesase 1 expression / J Clin Oncol 31(S):10526
Lan J / 2013 / Deficiency in expression and epigenetic DNA methylation of ASS1 gene in nasopharyngeal carcinoma: negative prognostic impact and therapeutic relevance / Tumour Biol 30
Possemato R / 2011 / Functional genomics reveal that the serine synthesis pathway is essential in breast cancer / Nature 476:346~350
Erez A / 2011 / Requirement of argininosuccinate lyase for systemic nitric oxide production / Nat Med 17:1619~1626
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