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Phenformin as an Anticancer Agent: Challenges and Prospects

Mª Eugenia García Rubiño1, Esmeralda Carrillo2,3,4,5,6, Gloria Ruiz Alcalá2,4

  • 1Department of Physical Chemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain.

International Journal of Molecular Sciences
|July 10, 2019
PubMed

Insights

Phenformin, a diabetes drug, shows promise as an anticancer agent by disrupting tumors and overcoming resistance to cancer therapies. Further research explores its potential in clinical trials.

Area of Science:

  • Oncology
  • Endocrinology
  • Pharmacology

Background:

  • Type 2 diabetes mellitus is linked to increased cancer risk via inflammation, hyperglycemia, and hyperinsulinemia.
  • Cancer treatment resistance to chemotherapy and antiangiogenic tyrosine kinase inhibitors (TKI) is a significant clinical challenge.
  • Phenformin, a biguanide antidiabetic drug, was withdrawn due to lactic acidosis risk but exhibits anticancer properties.

Purpose of the Study:

  • To review the anticancer potential of phenformin.
  • To elucidate phenformin's mechanisms of action in cancer.
  • To discuss clinical trials, challenges, and future perspectives of phenformin as an anticancer agent.

Main Methods:

  • Review of existing literature on phenformin, diabetes, and cancer.
  • Analysis of phenformin's biological pathways, including AMPK and mTOR.
  • Examination of clinical trial data and resistance mechanisms.

Main Results:

  • Phenformin acts as a tumor disruptor by inducing hypoglycemia and blocking the mTOR complex.
  • It enhances the efficacy of antiangiogenic tyrosine kinase inhibitors (TKI) by eliminating resistance.
  • Phenformin's anticancer effects are linked to energy metabolism regulation via AMPK.

Conclusions:

  • Phenformin demonstrates significant potential as an anticancer agent.
  • Its ability to overcome drug resistance and disrupt tumor growth warrants further clinical investigation.
  • Despite past safety concerns, phenformin's therapeutic benefits in oncology merit continued research and development.
Keywords:
biguanidescancercancer stem cellsdiabetes type 2phenformin

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