The Inhibitory Response to PI3K/AKT Pathway Inhibitors MK-2206 and Buparlisib Is Related to Genetic Differences in Pancreatic Ductal Adenocarcinoma Cell Lines
, Anett Sekora 1, Weibo Kong 1,2, Peter Bauer 1,3, Najim Ameziane 3,4, Ruslan Al-Ali 3, Susann Krake 3, Mandy Radefeldt 3, Frank Ulrich Weiss 5, Markus M. Lerch 5,6, Alisha Parveen 7, Dietmar Zechner 7, Christian Junghanss 1 and Hugo Murua Escobar 1,*
Round 1
Reviewer 1 Report
The research article by Yixuan Ma et al., presented the ‘Inhibitory Response to PI3K/AKT Pathway Inhibitors MK-2206 2 and Buparlisib is Related to Genetic Differences in Pancreatic 3 Ductal Adenocarcinoma Cell Lines’. In this article, authors suggested that blocking the PI3K/AKT pathway is an optional strategy for the treatment of PDAC patients, but it is still necessary to choose inhibitors based on the genetic background.
However, the current version of manuscript may need attention with respect to following recommendations.
- The language used in the manuscript in some places needs a major revision to conform to standard technical English.
- Since chemoresistance is a major problem associated with anti-cancer drugs, why did authors used drugs or inhibitors which are resisted by cancer cells lines. Refer to statement mentioned below:
Line-36-37: Moreover, increased resistance to MK-2206 was observed in cell lines carrying a KRAS variant, and increased resistance to both inhibitors was observed in SU.86.86 carrying two TP53 missense variants.
- Buparlisib is a potent and highly specific oral pan-class I PI3K inhibitor in low concentration. What is the appropriate concentration that inhibits target proteins?
- As mentioned, the data indicates that high expression of AKT2 is related to reducing the efficacy of Buparlisib. However, the further functional experiments are still need to verify the relationship of high AKT2 expression and Buparlisib resistance. How can you conclude that Buparlisib is possible treatment solution to PDAC patients?
- In conclusion section authors may concisely mention relationship explored between genetic data and the inhibitor response as an experimental set up.
- References need minor correction and modifications as per journal guidelines.
Author Response
Please see the attachment.
Author Response File: 
Author Response.docx
Reviewer 2 Report
I read with great interest the article "Inhibitory Response to PI3K/AKT Pathway Inhibitors MK-2206 and Buparlisib is Related to Genetic Differences in Pancreatic Ductal Adenocarcinoma Cell Lines” by Yixuan Ma, Sina Sender, Anett Sekora, Weibo Kong, Peter Bauer, Najim
Ameziane, Ruslan Al-Ali, Susann Krake, Mandy Radefeldt, Frank Ulrich Weiss,
Markus M. Lerch, Alisha Parveen, Dietmar Zechner, Christian Junghanss, and Hugo
Murua Escobar.
In my opinion, the article is well-written, structured and the material is well-chosen. Results correctly presented and extensively visualized. Discussion was conducted well.
The article presents the current knowledge on the very important topic of PI3K/AKT Pathway in the context of cancer.
In terms of research, I rate the work very highly. I believe that the work is fully understandable and does not require any corrections.
I believe that the article is suitable for printing in its current form.
Author Response
Responses to Reviewer 2 Comments:
I read with great interest the article "Inhibitory Response to PI3K/AKT Pathway Inhibitors MK-2206 and Buparlisib is Related to Genetic Differences in Pancreatic Ductal Adenocarcinoma Cell Lines” by Yixuan Ma, Sina Sender, Anett Sekora, Weibo Kong, Peter Bauer, Najim
Ameziane, Ruslan Al-Ali, Susann Krake, Mandy Radefeldt, Frank Ulrich Weiss,
Markus M. Lerch, Alisha Parveen, Dietmar Zechner, Christian Junghanss, and Hugo
Murua Escobar.
In my opinion, the article is well-written, structured and the material is well-chosen. Results correctly presented and extensively visualized. Discussion was conducted well.
The article presents the current knowledge on the very important topic of PI3K/AKT Pathway in the context of cancer.
In terms of research, I rate the work very highly. I believe that the work is fully understandable and does not require any corrections.
I believe that the article is suitable for printing in its current form.
Response: We greatly appreciate your acknowledgment of our work and for reading and evaluating our manuscript.
