Metformin and Melatonin in Adrenocortical Carcinoma: Morphoproteomics and Biomedical Analytics Provide Proof of Concept in a Case Study

Ann Clin Lab Sci. 2017 Aug;47(4):457-465.

Abstract

Metformin has been proposed as a novel anti-cancer drug for adrenocortical carcinoma (ACC) based upon Poli's recent preclinical studies that 1. "in vitro" metformin modulates the ACC cell model H295R and 2. "in vivo" metformin inhibits tumor growth in a xenograft model as confirmed by a significant reduction of Ki67 [1]. Here we report on our prior clinical case study that provides proof of concept for Poli's studies. We were requested to perform morphoproteomic analysis to further define the biology of, and raise targeted therapeutic options, for a case of post-treatment and chemoresistant ACC metastatic to the liver and the lung. Profiling the patient's ACC from the liver resulted in the recommendation of metformin as a maintenance therapy, which was supported by biomedical data analysis. The patient remains on maintenance therapy with metformin and melatonin and is free of disease some 7 years post diagnosis, thus underscoring the recommendation for clinical trials employing these therapeutic agents.

Keywords: Adrenocortical carcinoma; COX-2; EZH2 and SPARC pathways; beta-catenin; biology; biomedical analytics; c-Met; celecoxib; insulin-like growth factor; mTORC/Akt; melatonin; metformin; morphoproteomics; nab-paclitaxel; therapeutic options.

Publication types

  • Case Reports

MeSH terms

  • Adrenal Cortex Neoplasms / drug therapy
  • Adrenal Cortex Neoplasms / metabolism
  • Adrenal Cortex Neoplasms / pathology*
  • Adrenocortical Carcinoma / drug therapy
  • Adrenocortical Carcinoma / metabolism
  • Adrenocortical Carcinoma / pathology*
  • Adult
  • Antioxidants / therapeutic use
  • Biomarkers, Tumor / metabolism*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Immunohistochemistry
  • Melatonin / therapeutic use*
  • Metformin / therapeutic use*
  • Prognosis
  • Proteomics / methods*
  • Signal Transduction

Substances

  • Antioxidants
  • Biomarkers, Tumor
  • Hypoglycemic Agents
  • Metformin
  • Melatonin