A computational drug repositioning method applied to rare diseases: Adrenocortical carcinoma

Sci Rep. 2020 Jun 1;10(1):8846. doi: 10.1038/s41598-020-65658-x.

Abstract

Rare or orphan diseases affect only small populations, thereby limiting the economic incentive for the drug development process, often resulting in a lack of progress towards treatment. Drug repositioning is a promising approach in these cases, due to its low cost. In this approach, one attempts to identify new purposes for existing drugs that have already been developed and approved for use. By applying the process of drug repositioning to identify novel treatments for rare diseases, we can overcome the lack of economic incentives and make concrete progress towards new therapies. Adrenocortical Carcinoma (ACC) is a rare disease with no practical and definitive therapeutic approach. We apply Heter-LP, a new method of drug repositioning, to suggest novel therapeutic avenues for ACC. Our analysis identifies innovative putative drug-disease, drug-target, and disease-target relationships for ACC, which include Cosyntropin (drug) and DHCR7, IGF1R, MC1R, MAP3K3, TOP2A (protein targets). When results are analyzed using all available information, a number of novel predicted associations related to ACC appear to be valid according to current knowledge. We expect the predicted relations will be useful for drug repositioning in ACC since the resulting ranked lists of drugs and protein targets can be used to expedite the necessary clinical processes.

MeSH terms

  • Adrenal Cortex Neoplasms / drug therapy
  • Adrenal Cortex Neoplasms / pathology*
  • Adrenocortical Carcinoma / drug therapy
  • Adrenocortical Carcinoma / pathology
  • Computational Biology
  • Cosyntropin / therapeutic use
  • DNA Topoisomerases, Type II / metabolism
  • Drug Repositioning / methods*
  • Humans
  • Oxidoreductases Acting on CH-CH Group Donors / antagonists & inhibitors
  • Oxidoreductases Acting on CH-CH Group Donors / metabolism
  • Poly-ADP-Ribose Binding Proteins / antagonists & inhibitors
  • Poly-ADP-Ribose Binding Proteins / metabolism
  • Receptor, IGF Type 1 / antagonists & inhibitors
  • Receptor, IGF Type 1 / metabolism

Substances

  • IGF1R protein, human
  • Poly-ADP-Ribose Binding Proteins
  • Cosyntropin
  • Oxidoreductases Acting on CH-CH Group Donors
  • 7-dehydrocholesterol reductase
  • Receptor, IGF Type 1
  • DNA Topoisomerases, Type II
  • TOP2A protein, human