Targeting AKT/mTOR in Oral Cancer: Mechanisms and Advances in Clinical Trials

• Published in: International journal of molecular sciences Vol. 21; no. 9; p. 3285
• Main Authors: Harsha, Choudhary, Banik, Kishore, Ang, Hui Li, Girisa, Sosmitha, Vikkurthi, Rajesh, Parama, Dey, Rana, Varsha, Shabnam, Bano, Khatoon, Elina, Kumar, Alan Prem, Kunnumakkara, Ajaikumar B
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.05.2020; MDPI
• Subjects: Akt; AKT protein; Angiogenesis; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Autophagy; Cancer therapies; Carcinogenesis; Carcinogens; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Cell cycle; Cell growth; Cell proliferation; Chemoresistance; Circadian rhythms; Clinical trials; Clinical Trials as Topic; Cyclin-dependent kinases; Health services; Heterogeneity; Humans; inhibitors; Kinases; Lymphoma; Mesenchyme; Metabolism; Metastases; Mouth Neoplasms - drug therapy; Mouth Neoplasms - metabolism; mTOR; Oral cancer; Oral squamous cell carcinoma; pathway; Phagocytosis; Phosphorylation; Precision medicine; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Radio signals; Rapamycin; Review; Signal transduction; Signal Transduction - drug effects; Squamous cell carcinoma; Survival; Therapeutic applications; Tobacco; TOR protein; TOR Serine-Threonine Kinases - metabolism; treatment; Tumorigenesis; Asia; mTOR; inhibitors; treatment; pathway; Akt; oral cancer
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21093285

Oral cancer (OC) is a devastating disease that takes the lives of lots of people globally every year. The current spectrum of treatment modalities does not meet the needs of the patients. The disease heterogeneity demands personalized medicine or targeted therapies. Therefore, there is an urgent need to identify potential targets for the treatment of OC. Abundant evidence has suggested that the components of the protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) pathway are intrinsic factors for carcinogenesis. The AKT protein is central to the proliferation and survival of normal and cancer cells, and its downstream protein, mTOR, also plays an indispensable role in the cellular processes. The wide involvement of the AKT/mTOR pathway has been noted in oral squamous cell carcinoma (OSCC). This axis significantly regulates the various hallmarks of cancer, like proliferation, survival, angiogenesis, invasion, metastasis, autophagy, and epithelial-to-mesenchymal transition (EMT). Activated AKT/mTOR signaling is also associated with circadian signaling, chemoresistance and radio-resistance in OC cells. Several miRNAs, circRNAs and lncRNAs also modulate this pathway. The association of this axis with the process of tumorigenesis has culminated in the identification of its specific inhibitors for the prevention and treatment of OC. In this review, we discussed the significance of AKT/mTOR signaling in OC and its potential as a therapeutic target for the management of OC. This article also provided an update on several AKT/mTOR inhibitors that emerged as promising candidates for therapeutic interventions against OC/head and neck cancer (HNC) in clinical studies.