Possible therapeutic alternatives for HER2 tumors

One of the fundamental problems in the fight against cancer is that therapies that work well in some types of cancer may not work in other types.

An example of this lack of response to antitumor therapies is that of patients diagnosed with HER2 tumors.

Now, an investigation led by the group of Dr. Gema Moreno Bueno from the Autonomous University of Madrid (UAM) in Spain, the Alberto Sols Institute for Biomedical Research (dependent on the Higher Council for Scientific Research (CSIC) and the UAM) , the Cancer Network Biomedical Research Center (CIBERONC) and the MD Anderson Cancer Center Foundation (FMDA), have identified a new mechanism of therapeutic resistance to anti-HER2 therapies in HER2 breast and gastric tumors.

“Specifically, the work shows that the increase in the Gasdermin B (GSDMB) protein in response to anti-HER2 drugs causes the induction of pro-survival autophagy and subsequent resistance to these treatments, both in cell models of cancer and in various preclinical models. in vivo and in patient samples”, explains Dr. Moreno Bueno.

“Even more importantly -he highlights-, this protective response is specifically reversed with the combined treatment of antiHER2 therapy and autophagy inhibitors in tumors with high levels of GSDMB”.

This combinatorial therapy could be effective in aggressive tumors with overexpression of Gasdermin B and HER2 protein. And as a whole, the data show for the first time the mechanism of action of said protein in the lack of therapeutic response. In this context, it proposes new treatment alternatives for HER2 tumors with an adverse clinical prognosis.

Part of the research group led by Dr. Gema Moreno Bueno. (Photo: UAM)

To carry out this study, the researchers generated various in vitro approaches with a multitude of cell lines in which the levels of Gasdermin B (GSDMB) were genetically modified.

The data obtained were validated in vivo with various preclinical models (murines and zebrafish), in addition to biopsies from patients.

The study is titled “Gasdermin B over-expression modulates HER2-targeted therapy resistance by inducing protective autophagy through Rab7 activation.” And it has been published in the academic journal Journal of Experimental & Clinical Cancer Research. (Source: UAM)