Targeting PI3K/AKT/mTOR Signaling Pathway as a Radiosensitization in Head and Neck Squamous Cell Carcinomas

Yu-Chieh Su; Wei-Chang Lee; Chih-Chun Wang; Shyh-An Yeh; Wen-Hui Chen; Po-Jen Chen

doi:10.3390/ijms232415749

Targeting PI3K/AKT/mTOR Signaling Pathway as a Radiosensitization in Head and Neck Squamous Cell Carcinomas

Int J Mol Sci. 2022 Dec 12;23(24):15749. doi: 10.3390/ijms232415749.

Authors

Yu-Chieh Su^{1

2}, Wei-Chang Lee², Chih-Chun Wang^{1

3}, Shyh-An Yeh^{4

5}, Wen-Hui Chen⁶, Po-Jen Chen⁷

Affiliations

¹ Department of Medicine, School of Medicine, I-Shou University, Kaohsiung 840203, Taiwan.
² Division of Hematology-Oncology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 824410, Taiwan.
³ Department of Otolaryngology, E-Da Hospital, Kaohsiung 824410, Taiwan.
⁴ Department of Radiation Oncology, E-Da Hospital, Kaohsiung 824410, Taiwan.
⁵ Department of Medical Imaging and Radiological Sciences, I-Shou University, Kaohsiung 840203, Taiwan.
⁶ Department of Dentistry, E-Da Hospital, Kaohsiung 824410, Taiwan.
⁷ Department of Medical Research, E-Da Hospital, Kaohsiung 824410, Taiwan.

Abstract

Globally, there are over half a million new patients with head and neck squamous cell carcinomas (HNSCC) every year. The current therapeutic approaches to HNSCC are surgery and adjuvant radiotherapy. These approaches carry a high incidence of metastasis or recurrence from HNSCC cells' radioresistance. Recent studies have revealed that a combination with radiosensitizers can be used to improve the radioresistance in HNSCC; however, few agents are approved as radiosensitizers. The constitutive activation of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is a vitally oncogenic type of signaling that promotes tumorigenesis, metastasis, and radiotherapy resistance in HNSCC. Pharmacological targeting of PI3K/AKT/mTOR signaling pathway is considered a promising strategy of radiosensitization in HNSCC. In this review, we summarize the oncogenic significance of PI3K/AKT/mTOR signaling in HNSCC with radiotherapy resistance and highlight the therapeutic potential of small molecule inhibitors against PI3K/AKT/mTOR signaling for the radiosensitization in HNSCC treatment. It provides a mechanistic framework for the development of new drugs for radiosensitization in HNSCC radiotherapy via targeting PI3K/AKT/mTOR signaling pathway.

Keywords: PI3K/AKT/mTOR; head and neck cancer; radiosensitization; radiotherapy.

Publication types

Review

MeSH terms

Cell Line, Tumor
Head and Neck Neoplasms* / drug therapy
Head and Neck Neoplasms* / radiotherapy
Humans
Phosphatidylinositol 3-Kinase / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt* / metabolism
Signal Transduction
Squamous Cell Carcinoma of Head and Neck / drug therapy
Squamous Cell Carcinoma of Head and Neck / radiotherapy
TOR Serine-Threonine Kinases / metabolism

Substances

Proto-Oncogene Proteins c-akt
Phosphatidylinositol 3-Kinase
Phosphatidylinositol 3-Kinases
TOR Serine-Threonine Kinases
MTOR protein, human

Grants and funding

This study was supported by Ministry of Science and Technology, Taiwan (MOST- 09-2320-B-650 -001 -MY3), E-Da Hospital (EDPJ110053, EDPJ110047, EDPJ110080, EDAHS111012).