Receptor, Signal, Nucleus, Action: Signals That Pass through Akt on the Road to Head and Neck Cancer Cell Migration
Round 1
Reviewer 1 Report
I have no further suggestions, comments have been addressed sufficiently
Author Response
We appreciate your comments. Thanks
Reviewer 2 Report
The current review on Signals that pass 2 through Akt on the way to head and neck cancer cell migration by Alzawi et al. is well written and very informative. This review's findings will undoubtedly aid in investigating the role of the tumor microenvironment in activating the Akt signaling pathway and their crosstalk in head and neck cancer metastasis, potentially leading to the development of more effective novel combination targeted therapies. The authors covered the majority of the topics, and their findings may aid in improving HNSCC treatment in the future. Although this review is acceptable in its current form with minor revisions, there are a few points that the author should address to help the audience better understand relevant findings.
- An Akt inhibitor inhibits Akt activity, which may result in inhibition of the PI3K/Akt signaling pathway, thereby inhibiting cell proliferation, and inducing apoptosis in tumor cells, but it is unclear how it would avoid inhibiting T-cells, which are also the fastest proliferating cells in the body and are critical in the fight against cancer.
- The major challenges with current treatment strategies are high toxicity and unresolved acquired resistance to treatment (EGFR inhibitors, immunotherapy, etc.). How will Akt inhibitors in combination with other therapies help to solve this problem?
- In recent decades, signaling pathways have been popular targets for the design of therapeutic agents, but drug resistance has been observed, and recent findings suggest that this may be due to the TME and the Exosomes playing a role over there. It would be great if the author could elaborate on how signaling pathways inhibitors may play a role with exosomes, and how this will help to efficacious treatment.
Author Response
Thank you so much for the comments. We have now included the responses in the manuscript. Please see the attachment.
Author Response File: 
Author Response.docx
