Arginine Starvation and Docetaxel Induce c-Myc–Driven hENT1 Surface Expression to Overcome Gemcitabine Resistance in ASS1-Negative Tumors
نویسندگان
چکیده
منابع مشابه
Cisplatin-induced synthetic lethality to arginine-starvation therapy by transcriptional suppression of ASS1 is regulated by DEC1, HIF-1α, and c-Myc transcription network and is independent of ASS1 promoter DNA methylation
Many human tumors require extracellular arginine (Arg) for growth because the key enzyme for de novo biosynthesis of Arg, argininosuccinate synthetase 1 (ASS1), is silenced. These tumors are sensitive to Arg-starvation therapy using pegylated arginine deiminase (ADI-PEG20) which digests extracellular Arg. Many previous studies reported that ASS1 silencing is due to epigenetic inactivation of AS...
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Docetaxel (Taxotere), gemcitabine (Gemzar), and irinotecan (Camptosar, CPT-11) are active single agents in a variety of solid tumors. In combination, synergism may be schedule dependent. Preclinical studies suggested synergistic interactions when docetaxel was administered 24 hours before gemcitabine or irinotecan. The objective of this phase I trial in patients with refractory solid tumors was...
متن کاملGas6/Axl in arginine-starvation therapy
Exploiting abnormal amino acid metabolism for cancer therapy dated back to more than four decades ago by the discovery that L-asparaginase was effective in treating childhood acute lymphocytic leukemia (ALL). ALL lacks asparagine (Asn) because the key enzyme for the biosynthesis of Asn from aspartic acid, asparagine synthetase, is silenced, therefore, ALL requires Asn from the circulation for g...
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BACKGROUND Human equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection. METHODS Microarrays from 434 patients randomized to chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained with the 10D7G2 anti-hENT1 antibody. Patients were classified as having high hENT1...
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ژورنال
عنوان ژورنال: Clinical Cancer Research
سال: 2019
ISSN: 1078-0432,1557-3265
DOI: 10.1158/1078-0432.ccr-19-0206