jeffm34 wrote: Some comments from the researcher when asked about potential of TH1902 given her findings.
https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.15752
First of all, thank you for your interest in my work on sortilin and its implication in the development and progression of CRC as well as in the resistance to treatments, especially to 5-FU.
A cytotoxic targeting Sortilin seems very interesting and promising. Indeed, I had observed that sortilin could be a major player in the resistance of CRC cells to 5-FU, a molecule that has been the "basis" of chemotherapy protocols for years, particularly for the treatment of CRC. Indeed, its expression is considerably increased in 5-FU resistant cells. My work also focused on the CSC aspect: I had started to hypothesize that sortilin could be linked to these cells, especially in high grade tumors. This opened very interesting and promising perspectives.
Finally, in order to try to go further and understand how/why sortilin expression could be increased in 5-FU resistant cells, I had started experiments showing that, resistant cells had a significant disruption of the Golgi, that sortilin seemed to be accumulated inside and that its overexpression could be related to a decrease of ATF-3 expression.
I also noticed that all this was specific to sortilin (e.g. no variation in SorLA expression).
I noticed that Sortilin was overexpressed at several levels:
- membrane networks (subcellular fractionations): mainly plasma membrane + Golgi network
- nuclei
I also noticed that sortilin was secreted in the culture supernatants
This is a very short summary of the main information I can bring you. Do not hesitate to contact me if needed: I will be happy to work again on a project involving Sortiline and CRC!