A proteomic approach supports the clinical relevance of TAT-Cx43in glioblastoma.

in Translational research : the journal of laboratory and clinical medicine by Sara G Pelaz, Raquel Flores-Hernández, Tatjana Vujic, Domitille Schvartz, Andrea Álvarez-Vázquez, Yuxin Ding, Laura García-Vicente, Aitana Belloso, Rocío Talaverón, Jean-Charles Sánchez, Arantxa Tabernero

TLDR

  • TAT-Cx43 is a drug that can help fight a type of brain cancer called GBM. The study used a special tool to look at how TAT-Cx43 works in GBM cells. The study found that TAT-Cx43 works by stopping a protein called Src. The study also found that TAT-Cx43 helps other proteins in the body fight GBM. The study looked at how these proteins change in the body and found that some of these changes are linked to a better outcome for GBM patients. The study suggests that TAT-Cx43 could be used in clinical trials to help fight GBM.

Abstract

Glioblastoma (GBM) is the most frequent and aggressive primary brain cancer. The Src inhibitor, TAT-Cx43, exerts antitumor effects in in vitro and in vivo models of GBM. Because addressing the mechanism of action is essential to translate these results to a clinical setting, in this study we carried out an unbiased proteomic approach. Data-independent acquisition mass spectrometry proteomics allowed the identification of 190 proteins whose abundance was modified by TAT-Cx43. Our results are consistent with the inhibition of Src as the mechanism of action of TAT-Cx43and unveiled antitumor effectors, such as p120 catenin. Changes in the abundance of several proteins suggest that TAT-Cx43may also impact the brain microenvironment. Importantly, the proteins whose abundance was reduced by TAT-Cx43correlated with an improved GBM patient survival in clinical datasets and none of the proteins whose abundance was increased by TAT-Cx43correlated with shorter survival, supporting its use in clinical trials.

Overview

  • The study investigates the mechanism of action of TAT-Cx43, a Src inhibitor, in GBM. The study uses an unbiased proteomic approach with data-independent acquisition mass spectrometry to identify 190 proteins whose abundance is modified by TAT-Cx43. The results suggest that TAT-Cx43 inhibits Src as the mechanism of action and unveils antitumor effectors, such as p120 catenin. Changes in the abundance of several proteins suggest that TAT-Cx43 may impact the brain microenvironment. The study also correlates the proteins whose abundance is reduced by TAT-Cx43 with an improved GBM patient survival in clinical datasets, supporting its use in clinical trials.

Comparative Analysis & Findings

  • The study compares the outcomes observed under the treatment of GBM cells with TAT-Cx43 versus control cells. The results show that TAT-Cx43 inhibits Src as the mechanism of action and unveils antitumor effectors, such as p120 catenin. Changes in the abundance of several proteins suggest that TAT-Cx43 may impact the brain microenvironment. The study also correlates the proteins whose abundance is reduced by TAT-Cx43 with an improved GBM patient survival in clinical datasets, supporting its use in clinical trials.

Implications and Future Directions

  • The study's findings suggest that TAT-Cx43 may be a promising therapeutic option for GBM. The study's unbiased proteomic approach provides valuable insights into the mechanism of action of TAT-Cx43 and identifies potential antitumor effectors. The study's correlation with clinical datasets supports the use of TAT-Cx43 in clinical trials. Future research should focus on validating the findings in vivo and identifying potential combination therapies with other Src inhibitors or targeted therapies. The study's identification of changes in the brain microenvironment suggests that TAT-Cx43 may impact the tumor microenvironment, which could be further explored in future research.
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