The Gasdermina B protein, from executioner to savior

A recent study opens new avenues of research for the design of therapies in aggressive breast tumors.

The team has been led by Gema Moreno Bueno, Professor of Biochemistry at the Autonomous University of Madrid (UAM) and researcher at the Center for Biomedical Research in the Cancer Network (CIBERONC), both entities in Spain. David Sarrio and Sara Oltra Sanchís, from the UAM, have also worked in the studio.

Specifically, the results of the study will help to design therapies related to the Gasdermin B protein (GSDMB) in aggressive tumors. And they will also contribute to the identification of those patients with breast cancer who may have an adverse clinical evolution.

This is a collaborative work that has made it possible to unravel the molecular mechanism by which the Gasdermin B protein (GSDMB, originally considered to be protumoral), can exert an antitumor effect in breast cancer.

In other words, these results make it possible to identify those patients with breast cancer who would have an adverse clinical course, and open up new avenues of research for the design of therapies related to the Gasdermin B protein in aggressive tumors.

Pioneer study

A not inconsiderable number of HER2+ carcinomas, breast cancers with higher than normal levels of HER2, develop resistance, both innate and acquired, to specific treatments. Previous data have shown that the Gasdermin B protein (GSDMB) could be considered a biomarker of poor clinical prognosis in HER2+ breast carcinomas.

Breast cancer cells with higher than normal levels of HER2 are called HER2-positive. These cancers tend to grow and spread faster than other types of breast cancer, but they respond to treatment with drugs that target the HER2 protein.

Thus, these results reveal that activation of the protein causes proinflammatory death in tumor cells. This pioneering study characterizes for the first time the minimal region of GSDMB involved in cell death, being present only in some variants of the protein.

Clinical implication of the different GSDMB isoforms in HER2 breast cancer. (Image: Oltra et al. (2023))

The study is titled “Distinct GSDMB protein isoforms and protease cleavage processes differentially control pyroptotic cell death and mitochondrial damage in cancer cells”. And it has been published in the academic journal Cell Death and Differentiation. (Source: CIBERONC / UAM / IIBm / Cancer-CSIC Connection / MD Anderson / GEICAM Breast Cancer Research Group / Spanish Association Against Cancer)