A diagnostic microdosing approach to investigate platinum sensitivity in non-small cell lung cancer
| Autor: | Wang, Si-Si, Zimmermann, Maike, Zhang, Hongyong, Lin, Tzu-yin, Malfatti, Michael, Haack, Kurt, Turteltaub, Kenneth W., Cimino, George D., de Vere White, Ralph, Pan, Chong-xian, Henderson, Paul T. |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Lung Neoplasms Clinical Trials and Supportive Activities Oncology and Carcinogenesis Drug Resistance diagnostic microdosing Pilot Projects Article Mass Spectrometry predictive diagnostics Carboplatin Dose-Response Relationship DNA Adducts Clinical Research Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols accelerator mass spectrometry Humans Tissue Distribution platinum-based chemotherapy Carbon Radioisotopes Oncology & Carcinogenesis Non-Small-Cell Lung Lung non-small cell lung cancer Neoplasm Staging Aged Cancer Dose-Response Relationship Drug Carcinoma Lung Cancer Middle Aged Prognosis biomarkers of response Drug Resistance Neoplasm 5.1 Pharmaceuticals Neoplasm Female Cisplatin Drug Development of treatments and therapeutic interventions Follow-Up Studies |
| Zdroj: | International journal of cancer, vol 141, iss 3 |
| Popis: | The platinum-based drugs cisplatin, carboplatin and oxaliplatin are often used for chemotherapy, but drug resistance is common. The prediction of resistance to these drugs via genomics is a challenging problem since hundreds of genes are involved. A possible alternative is to use mass spectrometry to determine the propensity for cells to form drug-DNA adducts-the pharmacodynamic drug-target complex for this class of drugs. The feasibility of predictive diagnostic microdosing was assessed in non-small cell lung cancer (NSCLC) cell culture and a pilot clinical trial. Accelerator mass spectrometry (AMS) was used to quantify [14 C]carboplatin-DNA monoadduct levels in the cell lines induced by microdoses and therapeutic doses of carboplatin, followed by correlation with carboplatin IC50 values for each cell line. The adduct levels in cell culture experiments were linearly proportional to dose (R2 = 0.95, p |
| Databáze: | OpenAIRE |
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