Abstract
Most lung cancers are diagnosed at fairly advanced stages due to limited clinical symptoms. Platinum-based chemotherapy, either as single regimen or in combination with radiation, is one of the major recommendations for the patients. Earlier evaluation of the effectiveness of the chemotherapies is critical for developing better treatment plan given the toxicity of the chemotherapeutic reagents. Drug efficacy could be reflected in the systemic metabolism characteristics though knowledge about which remains scarce. In this study, serum metabolism influence of three types of commonly used platinum-based combination chemotherapy regimens, namely cisplatin with gemcitabine, vinorelbine or docetaxel, were studied using pattern recognition coupled with nuclear magnetic resonance techniques. The treated patients were divided into sensitive or insensitive subgroups according to their response to the treatments. We found that insensitive subjects can be identified from the sensitive ones with up-regulation of glucose and taurine but reduced alanine and lactate concentrations in serum. The combination chemotherapy of lung cancer is accompanied by disturbances of multiple metabolic pathways such as energy metabolism, phosphatidylcholine biosynthesis, so that the treated patients were marginally discriminated from the untreated. Serum metabolic profile of patients shows potential as an indicator of their response to platinum-based combination chemotherapy.
Highlights
Is important for developing more suitable treatment protocols, and reducing unnecessary exposure to the toxic drugs
Metabolism consequence of lung cancer targeted therapies has been characterized[22]; a study on human A549 cells treated with cisplatin suggested possibility of metabolite signatures as response to chemotherapy[23]; a pilot study on 25 patients before, during and after chemotherapy ± radiation treatments indicated that serum metabolites were strongly correlative with cancer stage and cancer type, and the prognosis[24]
orthogonal project to latent structure-discriminant analysis (OPLS-DA) classification models were established for every comparison inter-groups (Fig. 1), indicating discriminative metabolite profiles between the inter-groups
Summary
Is important for developing more suitable treatment protocols, and reducing unnecessary exposure to the toxic drugs. Metabolism consequence of lung cancer targeted therapies has been characterized[22]; a study on human A549 cells treated with cisplatin suggested possibility of metabolite signatures as response to chemotherapy[23]; a pilot study on 25 patients before, during and after chemotherapy ± radiation treatments indicated that serum metabolites were strongly correlative with cancer stage and cancer type, and the prognosis[24] These promising results somewhat justified the speculation that chemotherapy sensitivity might be elicited in drug-caused metabolism alteration even with the multifactorial nature of chemotherapy resistance and the lack of understanding on the impact of each factors
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