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Arginine dependence of tumor cells: targeting a chink in cancer’s armor

Oncogene volume 35, pages 49574972 (22 September 2016) | Download Citation

Abstract

Arginine, one among the 20 most common natural amino acids, has a pivotal role in cellular physiology as it is being involved in numerous cellular metabolic and signaling pathways. Dependence on arginine is diverse for both tumor and normal cells. Because of decreased expression of argininosuccinate synthetase and/or ornithine transcarbamoylase, several types of tumor are auxotrophic for arginine. Deprivation of arginine exploits a significant vulnerability of these tumor cells and leads to their rapid demise. Hence, enzyme-mediated arginine depletion is a potential strategy for the selective destruction of tumor cells. Arginase, arginine deiminase and arginine decarboxylase are potential enzymes that may be used for arginine deprivation therapy. These arginine catabolizing enzymes not only reduce tumor growth but also make them susceptible to concomitantly administered anti-cancer therapeutics. Most of these enzymes are currently under clinical investigations and if successful will potentially be advanced as anti-cancer modalities.

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Acknowledgements

MP gratefully acknowledges Department of Biotechnology (DBT), New Delhi, India for the award of Senior Research Fellowship. We are thankful to Professor Rakesh K Jain, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, USA; Dr Utpal Mohan, Department of Biotechnology, NIPER, Guwahati, India; and Dr Umesh Patil, School of Chemical Sciences, North Maharashtra University, Maharashtra, India for the assistance provided during preparation of the manuscript. We apologize to those authors whose work could not be cited owing to space limitations. Funding: This work was supported in part by National Institutes of Health (CA080124, CA096915, CA126642, CA197743).

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  1. Department of Pharmaceutical Technology (Biotechnology), National Institute of Pharmaceutical Education and Research, Punjab, India

    • M D Patil
    • , J Bhaumik
    •  & U C Banerjee
  2. Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    • S Babykutty
    •  & D Fukumura

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The authors declare no conflict of interest.

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Correspondence to D Fukumura.

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https://doi.org/10.1038/onc.2016.37

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