PI3K/AKT/mTOR pathway inhibitors: the ideal combination partners for breast cancer therapies?

Abstract

Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway is common in breast cancer. PI3K pathway activation has been associated with tumor growth and progression, and thus is a promising target for breast cancer therapy. Agents targeting the PI3K pathway can restore sensitivity to standard breast cancer therapies, including endocrine, HER2-targeted agents and chemotherapy, by suppressing PI3K pathway activation, which is central to the development of therapeutic resistance. The combination of endocrine therapy and PI3K pathway (mTOR) inhibition has proven clinical benefit, and novel combination strategies involving PI3K pathway inhibitors and other investigational targeted therapies are now being explored clinically in patients with breast cancer.

Keywords:

• AKT inhibitor
• breast cancer
• combination therapy
• mTOR inhibitor
• PI3K inhibitor

Financial & competing interests disclosure

J Abraham serves as an unpaid consultant for Pfizer. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. N Meinel and M Naylor provided medical editorial assistance on this manuscript. 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.

Key issues

• The PI3K/AKT/mTOR pathway plays a key role in drug resistance.

• An improved understanding of these pathways and the development of pathway-targeted therapies represents a major step in the future of cancer treatment.

• Clinical trials of several PI3K/AKT/mTOR pathway inhibitors are in progress, and enrolment in these trials may be recommended for eligible patients.

Notes