Table 3.
Relevant publications about mTORC2 complex–specific Rictor overexpression in different cancers
| Cancer type | Tumor subtype | Rictor overexpression data | Prognostic and therapeutic associations | References |
|---|---|---|---|---|
| Some latest pan-cancer data | Reviewed genetic alterations (frequent mutations of PI3K/Akt/mTOR pathways in lung, gastric, colorectal, renal, urinary bladder, prostate, and breast cancer and head and neck squamous cell carcinomas) in correlation with mTOR hyperactivity [323] | |||
| 435 cases (colorectal, gastric, renal, hepatocellular, lung cancers, cholangiocarcinoma, sarcomas, and other cancers); Rictor 78% positivity and 29% higher expression (with heterogeneous staining pattern) [344] | ||||
| Lung cancer | ||||
| SCLC | 6–15% amplification | ns | [344–347] | |
| Adenocarcinoma | 8–10% amplification; 37% overexpression (IHC) | Stage and brain metastasis could correlate | [334, 348] | |
| Metastatic lung cancers | 38% amplification | ns | [349] | |
| Lymphangioleiomyomatosis | 54% overexpression (IHC) | ns | [205] | |
| Additional importance | Rictor amplification–driven therapy has survival benefit in SCLC | [350] | ||
| Breast cancer | 37–50% overexpression (IHC) | Correlate with worse progression, metastasis Rictor mRNA correlate with worse outcome in patients with basal-like TN, mTOR hyperactivity, and metabolic plasticity correlates with worse prognosis | [128, 314, 318] | |
| TN | 41% overexpression (IHC) | [128, 330] | ||
| HER2 + | 58% overexpression (IHC) | |||
| Luminal A-B | 55% overexpression (IHC) | |||
| Lymph node metastasis | 92% overexpression (IHC) | [351] | ||
| Additional results: Rictor is an important mediator of chemotaxis and metastasis in breast cancer cells; BRCA1 loss is correlate with mTORC2 hyperactivity which can be targeted by mTORC2 inhibition | [352, 353] | |||
| Gastrointestinal cancer | ||||
| Gastric | Rictor mRNA, amplification, overexpression (IHC) 50–78% overexpression (IHC) | Rictor overexpression correlates with therapy resistance, worse prognosis, shorter OS; higher levels of Rictor/Akt correlate with poor survival, OS; mTORI combinations could be helpful in both EGFRI and platinum-based therapy of colon carcinomas; high mRNA-independent prognostic indicators for DFS | [349, 354–357] | |
| Colorectal | Rictor mRNA, overexpression (IHC) | [349, 355, 358, 359] | ||
| Esophageal squamous cell | 70% overexpression (IHC) | [360] | ||
| Hepatocellular, cholangiocarcinoma | mRNA | [361–363] | ||
| Head and neck cancer | 68–90% overexpression (IHC) | Higher stage and invasion | [360, 364–366] | |
| HPV-related OPSCC | mRNA, overexpression (IHC) | HPV is associated with Rictor overexpression, worse prognosis | [367] | |
| CNS malignancies | Glioma, glioblastoma | 64–86% overexpression (IHC) | mTORC2 could be a potential target in therapy | [368–371] |
| Pancreas cancer | 15% overexpression (IHC) | Decreased overexpression and promising results with mTORC1-2 inhibitors, mTORC2 activity marker correlates with worse survival | [372, 373] | |
| Prostate cancer | In vitro and other signaling failures data | ns | [372, 374] | |
| Renal cancer | Rapalog resistance in correlation with mTORC2 | [375] | ||
| Urogenital cancers | ||||
| Endometrial cancer | 44% overexpression (IHC) | Correlation with stage, metastasis, prognosis | [376] | |
| Bladder cancer | In vitro data | mTORC2 can mediate bladder cancer cell invasion | [377] | |
| Sarcoma | 20% overexpression (mainly leiomyosarcoma) overexpression (IHC) | High mTOR activity is associated with worse prognosis | [378] | |
| Rhabdomyosarcoma | 77% overexpression (IHC), 52% high mTORC2 | [207] | ||
| Myxofibrosarcoma | 42% amplification | [379] | ||
| Other cancers | ||||
| Lymphomas/leukemias | DLBCL (non-GC), AML, ALL, CLL, MCL, mRNA, experimental data, overexpression (IHC) | Higher mTORC2 activity correlates with worse prognosis, mTORC2 inhibition promising | [325, 380–385] | |
| Melanoma | mRNA | Liver metastasis in correlation with high Rictor expression; Rictor inhibition decrease metastasis | [386, 387] | |
| Pheochromocytoma | 80% overexpression (IHC) | ns | [388] | |