Table 4.
Preclinical studies exploring the role of PI3K, AKT and/or mTOR inhibitors radiosensitising other types of cancer.
| Author | Year | Type of Cancer | Experimental Model | Drug (s) Tested | Drug Category | Radiotherapy Dose | Summary Outcome |
|---|---|---|---|---|---|---|---|
| Detti et al. [106] | 2016 | Renal cell carcinoma (RCC) | Human patient case-report | Everolimus | mTOR inhibitor | Total dose = 20 Gy | RCC vertebral metastases treated successfully with radiotherapy and everolimus |
| Liu et al. [107] | 2014 | Hepatocellular Carcinoma | In vitro (cell lines): Huh7, BNL | BKM120 Rapamycin |
PI3K inhibitor mTOR inhibitor |
Variable range (0–10 Gy) |
Both drugs promoted apoptosis and reduced DSB break repair to a certain extent Dual inhibition with BKM120 and rapamycin significantly enhanced radiosensitivity of treated cells |
| Qiao et al. [108] | 2013 | Human Burkitt’s Lymphoma | In vitro (cell lines): Namalwa, Ramos, Raji | LY294002 SH-5 |
PI3K and PI3K-like kinase inhibitor AKT inhibitor |
5Gy | Enhanced apoptosis following treatment with the pathway inhibitors followed by radiotherapy |
| Fokas et al. (1) [77] | 2012 | Bladder (TCC) | In vitro (cell line): T24 | NVP-BEZ235 | PI3K and mTOR inhibitor | Variable range | Dual inhibitors enhance radiation-induced killing of endothelial cells |
| Endothelial cells | In vitro (cell line): HUVEC, HDMVC | NVP-BGT226 | PI3K and mTOR inhibitor | (0–6 Gy) | |||
| Fokas et al. (2) [76] | 2011 | Sarcoma | In vitro (cell line): HT-1080 HRE-Luc In vivo (xenograft): HT-1080 + mice |
NVP-BEZ235 BKM120 |
PI3K and mTOR inhibitor PI3K inhibitor |
6 Gy | Dual inhibitor modulated the tumour microenvironment Radiosensitised tumours by prolonging the time taken for normalisation of tumour vasculature |
| Murphy et al. [105] | 2009 | Sarcoma Endothelial cells |
In vitro (cell lines): SK-LMS-1 leiomyosarcoma, HT-1080 fibrosarcoma, SW-872 liposarcoma cells, In vitro (cell line): HDMEC |
Rapamycin | mTOR inhibitor | Variable range (0–6 Gy) |
Rapamycin radiosensitised all cell lines in vitro |
| Prevo et al. [23] | 2008 | Sarcoma Bladder (TCC) |
In vitro (cell line): HT-1080 T24 | PI-103 | PI3K, mTOR and DNA-PK Inhibitor | Variable (0–6 Gy) | Persistent DNA damage after treatment G2/M phase arrest |
| Manegold et al. [50] | 2008 | Endothelial cells | In vitro (cell line): HUVEC | Everolimus | mTOR inhibitor | 10 Gy or 20 Gy | Endothelial cells most sensitised to radiotherapy by mTOR inhibition |