Metformina come agente antitumorale

La metformina è un farmaco impiegato nelle condizioni di iperglicemia come ipoglicemizzante.

Oltre la sua funzione di abbassare il livello di zuccheri circolanti, è stato recentemente indagato quale agente in grado di interferire positivamente con l'omeostasi e la crescita cellulare e come agente idoneo alla prevenzione di alcune delle trasformazioni cellulari che esitano nel cancro.

La metformina ha dimostrato una certa attività di modulazione del sistema immunitario, dell'assetto ormonale corporeo, della crescita cellulare ed un effetto protettivo sull'endotelio vascolare.

Ulteriori studi sono in corso per verificare il suo impiego come agente adiuvante in condizioni oncologiche e come agente terapeutico da affiancare eventualmente a chemioterapia antiblastica, radioterapia, ipertermia.

  Dr. Carlo Pastore

J Diabetes. 2011 Feb 21. doi: 10.1111/j.1753-0407.2011.00119.x. [Epub ahead of print]

Metformin as an Antitumor Agent in Cancer Prevention and Treatment.

Li D.
Source:
Department of Gastrointestinal Medical Oncology, The University of Texas MD
Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.


Abstract:

Recent epidemiological investigations conducted in diabetic cohorts and cancer
patients have found that metformin users have lower risks for cancer than
insulin or insulin secretogogue users. Studies conducted in various animal
tumor models and cancer cell lines have demonstrated that metformin prevents
tumor development or inhibits cell proliferation. In addition, a recent
clinical trial has shown that short-term use of metformin reduced aberrant
crypt foci (ACF) formation in nondiabetic patients with ACF. The antitumor
activity of metformin could be mediated through its regulatory effect on
hormonal, metabolic, and immune functions. Metformin achieves glycemic control
by reducing hepatic glucose production and increasing the muscle intake of
glucose, thus lowering levels of circulating glucose and, consequently, of
insulin. The major molecular targets of metformin are the liver kinase B1 (LKB1)
-5'AMP-activated protein kinase (AMPK) signaling and mTOR pathways, which are
central to the regulation of cellular energy homeostasis and play a crucial
role in the control of cell division and cell proliferation. Metformin has been
shown to improve endothelial function, decrease inflammatory activity, and
regulate immune function. Increasing experimental evidence provides a strong
biological rationale for metformin as an antitumor and chemopreventive agent.
Metformin is being tested as an adjuvant cancer therapy in clinical settings,
and use of metformin is recommended for all cases of type 2 diabetes without
contraindications. As we show in the current review, the chemopreventive value
of this drug is not restricted to diabetic or obese individuals.

Copyright © 2011 Ruijin Hospital and Blackwell Publishing Asia Pty Ltd.