Individual responses to chemotherapy-induced oxidative stress.
Differences in redox homeostatic control between cancer patients may underlie predisposition to drug resistance and toxicities. To evaluate interindividual differences in redox response among newly diagnosed breast cancer patients undergoing standard chemotherapy, urine samples were collected before (T0), and at 1 (T1) and 24 h (T24) after chemotherapy administration. Oxidative status was assessed by urinary levels of allantoin and four F2-isoprostanes, quantified by LC-MS/MS. In all subjects, biomarker levels increased at T1 and returned to baseline at T24. Analyzing individual responses, two patterns were revealed: 10 subjects showed uniform increases of biomarker levels at T1 ("increase" pattern) and 8 subjects showed mixed (increase/unchanged/decrease) responses for different biomarkers ("mixed" pattern). The increase-pattern group had lower pre-treatment (T0) levels of the biomarkers and showed a sharp increase at T1 (64-141%) with a subsequent decrease at T24. The mixed-pattern group had higher pre-treatment biomarker levels and showed no change in biomarkers either at T1 or at T24. These findings indicate that there may be at least two distinct redox phenotypes with different homeostatic mechanisms balancing oxidative stress in humans. Recognizing redox phenotypes in human populations may lead to more precise assessment of health risks and benefits associated with individual redox make-up, and may also help to identify cancer patients who are especially susceptible to drug resistance and/or drug toxicity.
Il'yasova
Dora
D
Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, NC, 27710, USA. dora.ilyasova@duke.edu
Kennedy
Kelly
K
Spasojevic
Ivan
I
Wang
Frances
F
Tolun
Adviye A
AA
Base
Karel
K
Young
Sarah P
SP
Kelly Marcom
P
P
Marks
Jeffrey
J
Millington
David S
DS
Dewhirst
Mark W
MW
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000652:urine; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002853:Chromatography, Liquid; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000032:analysis; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D003520:Cyclophosphamide