Cancer Exacerbates Chemotherapy-Induced Sensory Neuropathy.
Cancer Res
; 80(13): 2940-2955, 2020 07 01.
Article
em En
| MEDLINE
| ID: mdl-32345673
For the constellation of neurologic disorders known as chemotherapy-induced peripheral neuropathy, mechanistic understanding and treatment remain deficient. Here, we present the first evidence that chronic sensory neuropathy depends on nonlinear interactions between cancer and chemotherapy. Global transcriptional profiling of dorsal root ganglia revealed differential expression, notably in regulators of neuronal excitability, metabolism, and inflammatory responses, all of which were unpredictable from effects observed with either chemotherapy or cancer alone. Systemic interactions between cancer and chemotherapy also determined the extent of deficits in sensory encoding and ion channel protein expression by single mechanosensory neurons, with the potassium ion channel Kv3.3 emerging as one potential contributor to sensory neuron dysfunction. Validated measures of sensorimotor behavior in awake, behaving animals revealed dysfunction after chronic chemotherapy treatment was exacerbated by cancer. Notably, errors in precise forelimb placement emerged as a novel behavioral deficit unpredicted by our previous study of chemotherapy alone. These original findings identify novel contributors to peripheral neuropathy and emphasize the fundamental dependence of neuropathy on the systemic interaction between chemotherapy and cancer. SIGNIFICANCE: These findings highlight the need to account for pathobiological interactions between cancer and chemotherapy as a major contributor to neuropathy and will have significant and immediate impact on future investigations in this field.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Receptoras Sensoriais
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Neoplasias Colorretais
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Biomarcadores Tumorais
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Regulação Neoplásica da Expressão Gênica
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Doenças do Sistema Nervoso Periférico
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Modelos Animais de Doenças
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Oxaliplatina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article