Work

Integrated Systems Pharmacology Analysis of Clinical Drug‐Induced Peripheral Neuropathy

Year: 2014

Type: article

Abstract: A systems pharmacology approach was undertaken to define and identify the proteins/genes significantly associated with clinical incidence and severity of drug-induced peripheral neuropathy (DIPN). Pharmacological networks of 234 DIPN drugs, their known targets (both intended and unintended), and the intermediator proteins/genes interacting with these drugs via their known targets were examined. A permutation test identified 230 DIPN-associated intermediators that were enriched with apoptosis and stress response genes. Neuropathy incidence and severity were curated from drug labels and literature and were used to build a predictive model of DIPN using a regression tree algorithm, based on the drug targets and their intermediators. DIPN drugs whose targets interacted with both v-myc avian myelocytomatosis viral oncogene homolog (MYC) and proliferating cell nuclear antigen-associated factor (PAF15) were associated with a neuropathy incidence of 38.1%, whereas drugs interacting only with MYC had an incidence of 2.9%. These results warrant further investigation in order to develop a predictive tool for the DIPN potential of a new drug.

Source: CPT Pharmacometrics & Systems Pharmacology

DOI: 10.1038/psp.2014.11

Authors: J Hur, AY Guo, WY Loh, EL Feldman, JPF Bai

Institutions: University of Michigan, University of Wisconsin–Madison, United States Food and Drug Administration, Center for Drug Evaluation and Research

Language: English

Topic: Cancer Treatment and Pharmacology

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,140