Skip to main content
. 2014 Nov 15;6(2):592–603. doi: 10.18632/oncotarget.2831

Figure 3. Androgen blockade plus mTOR inhibitors: A prime candidate for combination hormonal treatment.

Figure 3

The mTORC2/AKT/AR pathway (red arrows) leads to tumor cell proliferation. Rapamycin combined with bicalutamide has an apoptosis-inducing effect in prostate cancer. Rapamycin inhibits both mTOR complexes, mTORC1 with raptor and mTORC2 with rictor; nevertheless abrogation of mTORC2, a kinase for AKT phosphorylation, further inhibits the AR transcription cascade in an AKT-dependent manner. As a counterpoint, abrogation of mTORC1 produces AKT/AR-independent apoptosis, though it continues to stimulate the AR transcriptional cascade and AKT phosphorylation. According to the suggested cross-talk, it would take a combination of androgen blockade plus mTOR inhibitors to fully abrogate the mTORC2/AKT/AR pathway. Barnett et al. [44] found that, out of 47 tumors evaluable by immunohistochemistry, 36% had PTEN loss which was associated with an increased relapse in high risk prostate cancer treated with chemotherapy followed by surgery. PTEN loss activates the AKT/mTOR pathway [45] thus supporting the use of mTOR inhibitors in this condition. Abbreviations: AR, androgen receptor; AKT, aKT serine/threonine kinase.