Table 1.
Overview of Wnt/β-Catenin, Rapalogs, and Dual PI3K/mTOR Inhibitors Discussed in This Review
| Inhibitors | Target | Tested settings | Findings | References |
|---|---|---|---|---|
| Rapamycin | mTORC1 | Murine model | Inhibition of intestinal neoplasia in Apc mutant models | 93,95 |
| Everolimus | mTORC1 | Murine model | Reduced tumor burden in the ApcΔ716 mouse model | 92 |
| Everolimus | mTORC1 | CRC (phase II study) | Limited efficacy in metastatic CRC | 128 |
| Temsirolimus | mTORC1 | CRC (phase II study) | Limited efficacy in KRAS mutant CRC | 129 |
| Temsirolimus | mTORC1 | CRC cell lines | Reversed resistance to TNKSi | 144 |
| TAK228 | mTORC1/2 | Murine models and spheroids | Overcomes resistance to everolimus and induces response in PIK3CA mutant CRCs | 130 |
| PKI-587 | PI3K/mTORC | Solid tumors (phase I study) | Antitumor activity in patients resistant to conventional therapies | 131 |
| PKI-587 | PI3K/mTORC | CRC cell lines | Resistance to PKI-587 in PIK3CA mutant CRC cells | 135 |
| XL765 | PI3K/mTORC | Solid tumors (phase I study) | Antitumor activity in patients resistant to conventional therapies | 132 |
| BEZ235 | PI3K/mTORC | Solid tumors (phase I study) | No effect in patients with advanced solid tumors | 133 |
| LY3023414 | PI3K/mTORC | Solid tumors (phase I study) | Efficacy in patients with advanced solid tumors | 134 |
| LY3023414 | PI3K/mTORC | Murine models and spheroids | Potential treatment strategy in PIK3CA mutant CRCs | 137 |
| XAV939 | TNKS | Cell lines, patient-derived cells, murine models | Reversed resistance in patient-derived primary cultures and in corresponding xenograft tumors in mice | 147 |
| JW74 | TNKS | Cell lines and murine models | Decreased cell growth in CRC xenograft and reduced polyp formation in ApcMin/+ mice | 140 |
| G007-LK | TNKS | Cell lines and murine models | Reduced CRC cell line growth; tumor growth inhibition in Apc mutant CRC xenograft and genetically engineered CRC models | 141 |
| G007-LK | TNKS | Cell lines and murine models | Enhanced effect of PI3K (BKM120) and EGFR (erlotinib) inhibition in CRC cells and reduced growth of CRC xenografts in vivo | 145 |
| NVP-TNKS656 | TNKS | Cell lines, patient-derived cells, murine models | Overcomes resistance to PI3K or AKT inhibitors in CRC patient-derived sphere cultures and represses tumor growth in CRC-PDX models | 148 |
| NVP-TNKS656 | TNKS | Cell lines and murine models | Overcomes resistance to MEK inhibitors in CRC with KRAS and PIK3CA mutations | 151 |
| ETC-159 | PORCN | Murine models | Effective for treatment of RSPO translocation in CRC xenografts | 156 |
| LGK974 | PORCN | Cell lines and murine models | Loss of AXIN1 mediates resistance to LGK974 in CRC cells carrying RSPO3 fusions | 158 |
AXIN1, Axis inhibition protein 1; PDX, Patient derived xenografts.