Background: Constitutive activation of the PI3K/mTOR signaling pathway is observed in
most, if not all, breast cancers. Accordingly, many PI3K and/or mTOR inhibitors have entered clinical
trials, and completed studies should soon reveal the efficacy of these new drug families in the treatment
of cancer patients.
Objective: We present the PI3K/Akt/mTOR signaling pathway and the structure and the anti-tumor efficiency
of some mTOR inhibitors such as rapalogues and competitive inhibitors, which have entered
clinical trials. We also discuss some of the clinical trial results associated with these molecules mainly
focusing on studies performed on relapsing breast cancer patients - but not only.
Results: Most of the clinical trials with PI3K/mTOR inhibitors alone or in combination with chemotherapies
were performed in heavily pre-treated patients and revealed non-negligible amounts of partial responses and
long-term stable disease for these patients. Therefore, these compounds seem to prevent tumor growth and survival of
cancer cells in Human, representing a new range of anti-tumor drugs that can be utilized not only as first-line treatments
but as second- and third-line agents for patients who relapse.
Conclusion: Drugs inhibiting the PI3K/mTOR signaling pathway may represent tailored anti-tumor agents, paving the
way for their clinical application in different tumor types.