Overcoming endocrine resistance in breast cancer: importance of mTOR inhibition

Abstract

Approaches to treatment for many patients with advanced breast cancer are based on the expression of specific receptors. Treatments targeting the hormone receptor (typically the estrogen receptor) are used to reduce signaling through these receptors and thereby inhibit proliferation of breast cancer cells expressing these receptors. Although these treatments are effective for many patients, resistance to treatment is common. Recent clinical trials suggest that using multiple agents targeting the same pathway is not sufficient to overcome resistance. New treatment approaches are needed for these patients. Inhibition of the mTOR signaling pathway, a key point of confluence for multiple signaling cascades, offers a promising approach to restoring sensitivity to endocrine therapy in breast cancer. This article reviews the current data from studies of mTOR inhibitors everolimus and temsirolimus in combination with endocrine therapies to overcome treatment resistance in patients with advanced breast cancer.

Keywords::

• breast cancer
• endocrine
• everolimus
• mTOR
• resistance
• temsirolimus

Financial & competing interests disclosure

M Gnant has received consultancy fees (Novartis, Merrion), speaker’s fees (Roche, Amgen, Novartis, AstraZeneca, GlaxoSmithKline), and unrestricted grant/research funding (Roche, sanofi-aventis, GlaxoSmithKline, Novartis, AstraZeneca). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The author thanks T Fink and S Murthy for medical editorial assistance with this manuscript. Funding for medical editorial support was provided by Novartis Pharmaceuticals.