Targeting argininosuccinate synthetase in cancer therapy

Niramol Savaraj, Min You, Chunjing Wu, Macus Tien Kuo, Vy Dinh, Medhi Wangpaichitr, Lynn G Feun

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

There has been renewed interest in amino acid deprivation to treat various human cancers. Certain tumors do not express argininosuccinate synthetase (ASS) and therefore are unable to synthesize arginine from citrulline. These tumors are auxotrophic for arginine and may be inhibited by arginine deprivation. Arginine deprivation can affect growth and apoptotic signaling. In addition, mTOR signaling and RAF/MEK/ERK1/2 signaling are also affected by arginine deprivation. Upon arginine deprivation, tumor cells undergo autophagy as a survival mechanism, but prolonged autophagy can lead to apoptotic cell death. Arginine derivation using pegylated arginine deiminase (ADI-PEG20) has been shown to have activity in malignant melanoma and hepatocellular carcinoma with minimal side effects. Why ASS is silent in certain tumor types is not known. Aberrant DNA methylation which leads to epigenetic silencing has been reported. Reexpression of ASS may lead to resistance to arginine deprivation treatment. Thus, understanding how the ASS gene is regulated is very important for this modality of cancer treatment.

Original languageEnglish (US)
Title of host publicationCell Signaling & Molecular Targets in Cancer
PublisherSpringer New York
Pages37-51
Number of pages15
ISBN (Print)9781461407300, 146140729X, 9781461407294
DOIs
StatePublished - May 1 2011

ASJC Scopus subject areas

  • Medicine(all)

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    Savaraj, N., You, M., Wu, C., Kuo, M. T., Dinh, V., Wangpaichitr, M., & Feun, L. G. (2011). Targeting argininosuccinate synthetase in cancer therapy. In Cell Signaling & Molecular Targets in Cancer (pp. 37-51). Springer New York. https://doi.org/10.1007/978-1-4614-0730-0_3