Table 5.
Summary of the mTOR-based drug combinations investigated in various cancers.
| mTOR Inhibitor |
Combined with Drug |
Tumour Applied and Type of Study |
Outcome | Ref. |
|---|---|---|---|---|
| Everolimus | Trametinib (kinase inhibitor) |
Advanced solid tumours/ Phase 1B NCT00955773 |
Among 67 patients, 5 patients (7%) achieved partial response (PR) to treatment and 21 (31%) displayed stable disease (SD) | [146] |
| Everolimus | Lenvatinib (multiple receptor kinase inhibitor) |
RCC/Phase-II NCT01136733 |
Survival rate increased when used in combination | [139] |
| Everolimus | Carboplatin and paclitaxel | LCNEC/ Phase II NCT01317615 |
Improvement in overall response rate and tumour regression, combination is effective and well tolerated than using drug alone | [147] |
| Rapamycin | Entinostat (benzamide histone deacetylase inhibitor) |
General cancers/ In vitro |
This led to the halting of the cell cycle and the start of programmed cell death (apoptosis), it promotes MYC degradation | [148] |
| Rapamycin | AR inhibitor enzalutamide | HCC/ In vitro and In vivo |
Enalutamide and rapamycin together yielded stronger anti-HCC activity than each drug alone in vitro and in vivo. Also, combination exhibited more potent antitumour activity in the xenograft tumour model than cultured cancer cells, causing elevated apoptotic cell death and tumour regression | [149] |
| Rapamycin | STX-0119 | Glioblastoma/ In vitro |
Combining of two drugs had significant growth inhibitory effect against the TMZ-R U87 cell line. IC50 decreased to 11.3μM (drug combination) from 78 μM (STX-0119) and 30.5 μM (rapamycin) |
[150] |
AR: androgen receptor, HCC: hepatic cell carcinoma, LCNEC: large-cell neuroendocrine carcinoma, RCC: renal cell carcinoma.