The increasing knowledge of molecular alterations in malignancies, including mutations
and regulatory failures in the mTOR (mechanistic target of rapamycin) signaling pathway,
highlights the importance of mTOR hyperactivity as a validated target in common and
rare malignancies. This review summarises recent findings on the characterization
and prognostic role of mTOR kinase complexes (mTORC1 and mTORC2) activity regarding
differences in their function, structure, regulatory mechanisms, and inhibitor sensitivity.
We have recently identified new tumor types with RICTOR (rapamycin-insensitive companion
of mTOR) amplification and associated mTORC2 hyperactivity as useful potential targets
for developing targeted therapies in lung cancer and other newly described malignancies.
The activity of mTOR complexes is recommended to be assessed and considered in cancers
before mTOR inhibitor therapy, as current first-generation mTOR inhibitors (rapamycin
and analogs) can be ineffective in the presence of mTORC2 hyperactivity. We have introduced
and proposed a marker panel to determine tissue characteristics of mTOR activity in
biopsy specimens, patient materials, and cell lines. Ongoing phase trials of new inhibitors
and combination therapies are promising in advanced-stage patients selected by genetic
alterations, molecular markers, and/or protein expression changes in the mTOR signaling
pathway. Hopefully, the summarized results, our findings, and the suggested characterization
of mTOR activity will support therapeutic decisions.