Data from Microdose-Induced Drug–DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice Article Swipe

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Maike Zimmermann , Sisi Wang , Hongyong Zhang , Tzu‐yin Lin , Michael Malfatti , Kurt Haack , Ted Ognibene , Hongyuan Yang , Susan Airhart , Kenneth W. Turteltaub , George D. Cimino , Clifford G. Tepper , Alexandra Drakaki , Karim Chamie , Ralph de Vere White , Chong-xian Pan , Paul T. Henderson ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1158/1535-7163.c.6537576

We report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [¹⁴C]carboplatin (1% of the therapeutic dose). Carboplatin–DNA adducts were quantified by accelerator mass spectrometry in blood and tumor samples collected within 24 hours, and compared with subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels. Four patient-derived bladder cancer xenograft mouse models were used to test the possibility that another drug in the regimen could cause a response. The mice were dosed with [¹⁴C]carboplatin or [¹⁴C]gemcitabine and the resulting drug–DNA adduct levels were compared with tumor response to chemotherapy. At least one of the drugs had to induce high drug–DNA adduct levels or create a synergistic increase in overall adducts to prompt a corresponding therapeutic response, demonstrating proof-of-principle for drug–DNA adducts as predictive biomarkers. Mol Cancer Ther; 16(2); 376–87. ©2016 AACR.

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Adductor Pollicis Muscle

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Carboplatin MicroDose Adduct Chemotherapy Chemistry Gemcitabine Cancer research Accelerator mass spectrometry Drug Pharmacology Cancer DNA adduct Internal medicine Medicine Cisplatin Mass spectrometry Organic chemistry Chromatography

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1158/1535-7163.c.6537576
OA Status: gold
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OpenAlex ID: https://openalex.org/W4362495138

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DOI: https://doi.org/10.1158/1535-7163.c.6537576

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Title: Data from Microdose-Induced Drug–DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice

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Language: en

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Publication year: 2023

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Publication date: 2023-04-03

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Authors: Maike Zimmermann, Sisi Wang, Hongyong Zhang, Tzu‐yin Lin, Michael Malfatti, Kurt Haack, Ted Ognibene, Hongyuan Yang, Susan Airhart, Kenneth W. Turteltaub, George D. Cimino, Clifford G. Tepper, Alexandra Drakaki, Karim Chamie, Ralph de Vere White, Chong-xian Pan, Paul T. Henderson

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Landing page: https://doi.org/10.1158/1535-7163.c.6537576

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Concepts: Carboplatin, MicroDose, Adduct, Chemotherapy, Chemistry, Gemcitabine, Cancer research, Accelerator mass spectrometry, Drug, Pharmacology, Cancer, DNA adduct, Internal medicine, Medicine, Cisplatin, Mass spectrometry, Organic chemistry, Chromatography

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abstract_inverted_index.[<sup>14</sup>C]carboplatin	27, 100
abstract_inverted_index.[<sup>14</sup>C]gemcitabine	102
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