Therapeutic potential of inhibition of autophagy in breast cancer treatment

MARIO ROSSI; FABIANA ROSSI; MARTIN RIVERO

Buenos Aires

Congreso; Frontiers in Bioscience 2; 2016

IBioBA MPSP CONICET

The autophagic pathway is one of the most important degradative metabolic pathways and its main function is to promote cell survival under conditions of metabolic stress. In this regard, in recent year the study and characterization of new drugs that function as inhibitors of the autophagic flow have attracted much attention because of their great potential for the future development of new treatments to improve the clinical management of cancer patients. In this sense, research studies by our group and others have shown that a family of tricyclic compounds used clinically to treat psychiatric disorders have inhibitory activity on the autophagic flux. In addition we have demonstrated that these compounds can sensitize tumor cell to the action of Doxorubicin, a common chemotherapeutic agent used in the treatment of a wide variety of cancers.Based on these observations, we are extending and validating in animal models our studies to determine the potential therapeutic value of tricyclic anti-depressants as coadjutants in anti-tumor treatments. To this end we are using a cellular model derived from a particular subtype of breast cancer called "triple negative" (TNBC), against which there is currently no specific treatment and, although they can be treated with chemotherapy, they tend to be recurrent and produce early metastasis. Recently it has been shown that in TNBC, the autophagic pathway plays an essential role as a mechanism for the maintenance of cellular homeostasis, highlighting its potential as a possible point of therapeutic intervention in cancer treatment.