Overcoming endocrine resistance in breast cancer: role of the PI3K and the mTOR pathways

Abstract

Overcoming endocrine resistance is a 21st century hurdle in the treatment of hormone receptor-positive breast cancers. Estrogen plays a role in the growth of 70% of breast cancers. There are many strategies evolved to overcome estrogen resistance. Established strategies include using drugs such as tamoxifen, a selective estrogen receptor modulator to selectively block estrogen receptors and aromatase inhibitors to decrease the synthesis of estrogen. However, endocrine resistance is commonly encountered in treating patients with standard single-therapy regimens. Recently, the role of the PI3K and the mTOR pathways has been targeted to overcome resistance. The mTOR pathway is a complex pathway regulating cell metabolism, growth and apoptosis. Novel agents such as mTOR inhibitors, PI3K inhibitors and Akt inhibitors are transitioning from bench-top research to clinical application with promising results. This article reviews the common mechanisms of endocrine resistance, and combination therapies that utilize the mTOR/PI3K pathways to overcome resistance.

Keywords::

• breast cancer
• endocrine resistance
• mTOR
• PI3K

Financial & competing interest disclosure

The authors have no 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 this manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.