Argininosuccinate synthetase (ASS) deficiency in high-grade pulmonary neuroendocrine carcinoma: an opportunity for personalized targeted therapy

Purpose Cells deficient in argininosuccinate synthetase (ASS) must absorb the arginine they need for growth from circulating blood. Treatment with pegylated arginine deiminase (ADI-PEG 20) selectively eliminates arginine from the circulation and has shown some efficacy against ASS-deficient tumors i...

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Bibliographic Details
Published in:Journal of cancer research and clinical oncology 2015-08, Vol.141 (8), p.1363-1369
Main Authors: Walts, Ann E., Bomalaski, John S., Ines, Delma, Orsulic, Sandra
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Argininosuccinate Synthase - deficiency
Cancer Research
Carcinoma, Neuroendocrine - enzymology
Carcinoma, Neuroendocrine - pathology
Carcinoma, Neuroendocrine - therapy
Enzymes
Female
Hematology
Humans
Hydrolases - therapeutic use
Immunohistochemistry
Internal Medicine
Lung cancer
Lung Neoplasms - enzymology
Lung Neoplasms - pathology
Lung Neoplasms - therapy
Male
Medicine
Medicine & Public Health
Middle Aged
Molecular Targeted Therapy - methods
Neoplasm Grading
Oncology
Original Article – Cancer Research
Pathology
Patient Selection
Polyethylene Glycols - therapeutic use
Precision medicine
Precision Medicine - methods
Small Cell Lung Carcinoma - epidemiology
Small Cell Lung Carcinoma - metabolism
Small Cell Lung Carcinoma - pathology
Small Cell Lung Carcinoma - therapy
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Summary:Purpose Cells deficient in argininosuccinate synthetase (ASS) must absorb the arginine they need for growth from circulating blood. Treatment with pegylated arginine deiminase (ADI-PEG 20) selectively eliminates arginine from the circulation and has shown some efficacy against ASS-deficient tumors including small cell lung cancer (SCLC). We sought to assess ASS expression in a cohort of high-grade pulmonary neuroendocrine carcinomas (PNEC) which include SCLC and large cell neuroendocrine carcinoma (LCNEC). Methods Sixty-nine PNEC (49 SCLC and 20 LCNEC) were retrieved from our pathology archives. Formalin-fixed paraffin-embedded sections of the 54 primary tumors, 15 metastases and appropriate positive and negative controls were immunostained using an ASS-specific monoclonal antibody. Positive staining in
ISSN:0171-5216
1432-1335
DOI:10.1007/s00432-014-1904-z