Trials in mTOR inhibition

This article reviewed the significance of the mTOR protein in breast cancer patients and its potential as a target for cancer treatments.

Current cancer treatments are often based on specific molecular activities of the cancer important for tumor growth and spread. For example, since the hormone estrogen plays a role in cell growth stimulation, treatment of hormone receptor-positive breast cancer often includes drugs which block the production of estrogen, or its effect on estrogen receptors. The drug trastuzumab (Herceptin) is another example of a molecular targeting drug used to treat women with human epidermal growth factor receptor 2 (HER2) positive breast cancer.

The mTOR protein is a molecule normally responsible for cell growth, division and survival. Drugs that inhibit the actions of mTOR have been the focus of recent cancer treatment research. Various mTOR inhibitors, such as everolimus (Afinitor), temsirolimus (Torisel) and sirolimus (Rapamune) are currently being investigated in clinical trials including breast cancer patients.

In one early phase study, everolimus was given to advanced hormone receptor-positive breast cancer patients in addition to hormonal therapy. 68.1% of patients treated with combined everolimus and hormonal therapy showed reduction in tumor size compared to only 59.1% of patients treated with hormonal therapy and a placebo. A similar trial involving recurrent breast cancer patients showed that everolimus in combination with hormonal therapy nearly doubled the time until progression of the disease compared to hormonal treatment alone. The risk for disease progression despite treatment in the same trial was found to be reduced by 46% with the addition of everolimus to hormonal therapy.

Research into the use of mTOR inhibitors for the treatment of HER2-positive breast cancer patients is still in early phases. A phase one trial investigating the combination of everolimus and trastuzumab demonstrated that the combination is well tolerated and safe to use. Preliminary results from a phase II trial among recurrent breast cancer patients reported that everolimus in combination with trastuzumab and chemotherapy resulted in a stable disease (no additional growth of the cancer for 6 months) in up to 62% of patients. A large, controlled, phase III trial investigating everolimus as first choice treatment for HER2-positve breast cancer patients is currently underway.

This review concluded that mTOR inhibitors, in combination with current cancer therapies, may reduce disease progression and increase treatment success rates.

Some of the writers of this review have declared to have received funds from various pharmaceutical companies that produce mTOR inhibitors.

Consult with your physician regarding the potential benefit of combining current therapies with mTOR inhibitors.