Table 1.
Molecular events in the mTOR pathway involved in cancer drug resistance
| Molecular events | Resistance to | Tumor/cell types | Refs |
|---|---|---|---|
| Overexpression of mTOR and p70S6K1 | TRAIL | Glioblastoma | (Panner et al., 2005) |
| Defect in the regulation of 4EBP1 and 4EBP2 | Retinoid acid | NB4 cell | (Grolleau et al., 2000) |
| MTOR activation | Vincristine | FL5.12 cells | (Vanderweele and Rudin, 2005) |
| PI3K regulates MDR1 expression | Vincristine | Leukemia | (Tazzari et al., 2007) |
| PI3K regulates MDR1 expression | Vincristine | Prostate cancer | (Lee, Jr. et al., 2004) |
| Activation of PI3K and AKT | Trastuzumab | Breast cancer | (Berns et al., 2007) |
| Activation of PI3K and AKT | Endocrine therapy | Breast cancer | (Tokunaga et al., 2006) |
| Constitutive AKT activation | Tamoxifen | Breast cancer | (Campbell et al., 2001; Clark et al., 2002; Frogne et al., 2005) |
| PIK3CA mRNA amplification and PTEN loss | Cisplatin | Ovarian cancer | (Lee et al., 2005) |
| AKT inhibits p53 phosphorylation | Cisplatin | Ovarian cancer | (Fraser et al., 2008) |
| Constitutive AKT activation | TRAIL | Prostate Cancer | (Chen et al., 2001) |
| Constitutive AKT activation | TRAIL | Leukemia | (Bortul et al., 2003) |
| Up-regulation of phosphorylated AKT | Erlotinib | Epidermoid cancer cell A-431 | (Yamasaki et al., 2007) |
| Activation of PI3K and AKT | Taxol | Hematopoietic cells | (Liu et al., 2006c) |
| Activation of PI3K and AKT | Arsenic trioxide | Leukemia | (Tabellini et al., 2005) |
| Activation of PI3K and AKT | All-trans-retinoic acid | Leukemia | (Neri et al., 2003) |
| Activation of PI3K and AKT | Imatinib | Gastrointestinal stromal tumor | (Bauer et al., 2007) |
| AKT phosphorylation and PTEN loss | Etoposide and doxorubicin | Gastric cancer | (Yu et al., 2008) |
| AKT phosphorylation and PTEN loss | Doxorubicin | Bladder cancer | (Tanaka and Grossman, 2003) |
| AKT1 amplification and overexpression | Cisplatin | Lung cancer | (Liu et al., 2007) |
| AKT1 activation | Taxol | Hepatoma cells | (Lin et al., 2003) |
| Constitutively active AKT2 expression | Cisplatin | Ovarian cancer | (Yuan et al., 2003) |
| AKT2 and AKT3 overexpression | Cisplatin | Uterine cancer | (Gagnon et al., 2004) |
| EGFR, AKT1 and ERK1 activation | Cisplatin | Breast cancer | (Eckstein et al., 2008) |
| Raf activation | Doxorubicin and paclitaxel | Breast cancer | (McCubrey et al., 2006) |
| MEK/ERK regulates MDR1 expression | Doxorubicin and paclitaxel | Colorectal cancer | (Katayama et al., 2007) |
| ERK-MKP-1 activation | Cisplatin | Ovarian cancer | (Wang et al., 2007) |
| ERK1/2 and p38 activation | Cisplatin | Ovarian cancer | (Villedieu et al., 2006) |
| ERK activation | Tamoxifen | Breast cancer | (Cui et al., 2006; Svensson et al., 2005) |
| ERK activation | TRAIL | Breast cancer | (Lee et al., 2006) |
| Activation of AKT and ERK | Etoposide | Gastric cancer | (Liu et al., 2006b) |
| Activation of AKT and ERK | ZD1839 or PD153035 | Gliomas | (Li et al., 2003) |
| ERK activation, JNK and p38MAPK inhibition | Doxorubicin | Prostate Cancer | (Lin et al., 2005) |
| ERK activation | Gefitinib | NSCLC | (Han et al., 2005) |
| ERK activation | 5-fluorouracil | Pancreatic cancer | (Zhao et al., 2006) |
| ERK activation | Vincristine | Leukemia | (Kisucka et al., 2001) |
| MKP-1/JNK activation | Cisplatin | MEF cells | (Wang et al., 2006b) |
| JNK activation | Tamoxifen | Breast cancer | (Cui et al., 2006) |
TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; MDR1, multidrug resistance-associated protein 1; NSCLC, non-small cell lung cancer; MEFs, mouse embryonic fibroblasts.