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A multidisciplinary team led by Dr. Gema Moreno Bueno, from the Instituto de Investigaciones Biomédicas Alberto Sols, IIBM (CSIC-UAM), has discovered new functions of the protein Gasdermin B that will further research into the design of therapies for aggressive breast tumours.
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This research, which represents a glimmer of hope for breast cancer patients with a poor prognosis, has just been published in the prestigious journal Cell Death and Differentiaton
Dr. Gema Moreno Bueno, Professor at the Autonomous University of Madrid and Researcher at the IIBM (CSIC-UAM), the MD Anderson Foundation, head of the Cancer Biomedical Research Network Centre (CIBERONC) and Conexión Cáncer-CSIC, together with Dr. David Sarrio (CIBERONC), and Dr. Sara S Oltra (postdoctoral researcher), have just been published in the prestigious journal Cell Death and Differentiation. Sara S Oltra (postdoctoral researcher thanks to a grant from the Spanish Association Against Cancer) among other researchers, have published a study that explores the molecular mechanism by which the protein Gasdermin B (GSDMB) can exert an antitumour effect in breast cancer.
Until now it was thought that high levels of this protein had a pro-tumour effect. In fact, in October 2022, this team of researchers published the relationship between GSDMB and resistance to some breast cancer treatments and how to avoid this resistance. However, the team led by Dr Moreno Bueno has confirmed that this is not always the case. In fact, there are four different variants of the GSDMB protein; some favour the development of breast cancer while others promote an anti-tumour effect.
The researchers have identified the exact region of the GSDMB protein responsible for the anti-tumour effect. They have also been able to determine that it is a small part of this protein, which is present only in some variants, that causes the death of breast cancer tumour cells. These data were confirmed in samples derived from breast cancer patients, in which it was found that the differential expression of the different GSDMB isoforms (with and without the ability to promote cell death) is associated with various clinicopathological variables. Thanks to this study it is now possible to identify those breast cancer patients who would have an adverse clinical evolution and opens new avenues of research for the design of therapies directed against GSDMB in aggressive tumours.
Figure. Clinical implication of the different GSDMB isoforms in HER2 breast cancer.
Dr. Paulino Gómez (CBM, Conexión Cáncer-CSIC) has also collaborated in this study, published in the journal Cell Death and Differentiaton, and has been funded by the Spanish Ministry of Science and Innovation and the Spanish Association Against Cancer. Part of this work is the result of the collaboration between CIBERONC and the GEICAM Breast Cancer Research group through the seed project awarded to Dr. Moreno Bueno's team. This project is aimed at analysing the multicentre, prospective observational study ConvertHER (GEICAM/2009-03) in patients with breast cancer, led by Dr Joan Albanell and Dr Ana Lluch and in which Dr Federico Rojo also participated.