Dr Roberta Bonomo
About
My research project
Metabolic markers in Chemotherapy-induced peripheral neuropathyMore than 2 million Europeans receive a diagnosis of cancer yearly, and more than a half of them are candidates to be treated with antineoplastic drugs which are neurotoxic on the PNS (Chemotherapy-Induced Peripheral Neurotoxicity, CIPN). Paclitaxel and oxaliplatin are the cornerstones of the treatment of breast and colorectal cancers, i.e. the most frequent cancer in women and the second most frequent in men, respectively. Several modifications involved in aging PNS have been hypothesized to underlie age-related susceptibility to damage or impaired regeneration/repair after damage, such as reduced plasticity, impaired functionality of local blood circulation and of the oxidative stress scavenger, modification in growth factors support. However, the results of these studies are inconclusive and other targets, possibly available to be used as biomarkers of PNS functioning in the future, deserve to be investigated. The metabolome is the final downstream product of the genome and is closest to the functional phenotype of the cell or organism. Study thereof can give more direct answers than the proteome or transcriptome. Moreover, analysis of the metabolome looks more attractive than the analysis of the proteome or transcriptome since it consists of <10 000 estimated small molecules in contrast to the millions or tens of thousands of proteins, transcripts and genes. Therefore, specific metabolite profiles and metabolomic signatures are considered promising as putative useful tools for improving understanding of the mechanistic processes of the corresponding disease and for identifying specific metabolic markers. Moreover, age has been suggested as a probable risk factor for more severe CIPN and increased mordibity has been observed in aged persons with CIPN compared to healthy, age-matched persons.
This project will include neurotoxicity experiments based on a CIPN study comparing the effect of paclitaxel-based chemotherapy in young (2 months of age) and adult (9 months of
age) rats with the aim comparing at the phenotypic and metabolic level the effects of treatment according to the different ages.
Supervisors
More than 2 million Europeans receive a diagnosis of cancer yearly, and more than a half of them are candidates to be treated with antineoplastic drugs which are neurotoxic on the PNS (Chemotherapy-Induced Peripheral Neurotoxicity, CIPN). Paclitaxel and oxaliplatin are the cornerstones of the treatment of breast and colorectal cancers, i.e. the most frequent cancer in women and the second most frequent in men, respectively. Several modifications involved in aging PNS have been hypothesized to underlie age-related susceptibility to damage or impaired regeneration/repair after damage, such as reduced plasticity, impaired functionality of local blood circulation and of the oxidative stress scavenger, modification in growth factors support. However, the results of these studies are inconclusive and other targets, possibly available to be used as biomarkers of PNS functioning in the future, deserve to be investigated. The metabolome is the final downstream product of the genome and is closest to the functional phenotype of the cell or organism. Study thereof can give more direct answers than the proteome or transcriptome. Moreover, analysis of the metabolome looks more attractive than the analysis of the proteome or transcriptome since it consists of <10 000 estimated small molecules in contrast to the millions or tens of thousands of proteins, transcripts and genes. Therefore, specific metabolite profiles and metabolomic signatures are considered promising as putative useful tools for improving understanding of the mechanistic processes of the corresponding disease and for identifying specific metabolic markers. Moreover, age has been suggested as a probable risk factor for more severe CIPN and increased mordibity has been observed in aged persons with CIPN compared to healthy, age-matched persons. This project will include neurotoxicity experiments based on a CIPN study comparing the effect of paclitaxel-based chemotherapy in young (2 months of age) and adult (9 months of age) rats with the aim comparing at the phenotypic and metabolic level the effects of treatment according to the different ages.
Publications
Introduction: Metabolomics is an emerging approach providing new insights into the 7 metabolic changes and underlying mechanisms involved in the pathogenesis of 8 neurological disorders. 9 Areas covered: Here, we present an overview of the current knowledge of metabolic 10 profiling (metabolomics) to provide critical insight on the role of biochemical markers and metabolic alterations in neurological diseases. Expert opinion: Elucidation of characteristic metabolic alterations in neurological disorders is crucial for a better understanding of their pathogenesis, and for identifying potential biomarkers and drug targets. Nevertheless, discrepancies in diagnostic criteria, sample handling protocols, and analytical methods still affect the generalizability of current study results.