2025/12/03
A study led by CIC bioGUNE explores how alterations in cancer cells change the architecture of prostate tumors and provide insight into disease aggressiveness
The work focuses on integrating approaches used in routine clinical practice with cutting-edge technologies to advance the understanding of prostate cancer.
This is a multidisciplinary study that brings together expert teams in computational biology, pathology, fundamental cancer biology, and oncological urology from Bizkaia. The research teams combine the analysis of the PTEN protein in tumors with the study of thousands of genes, bioinformatic algorithms, and validations in mouse models.
The research has been led by investigators Arkaitz Carracedo and Isabel Mendizabal at CIC bioGUNE, with funding from the European Marie Curie programs, Ikerbasque, and CIBERONC.
Prostate cancer is one of the most common tumors in men, but its behavior is highly variable: some tumors grow very slowly, while others progress aggressively. One of the most frequent alterations in tumors with poor outcomes is the loss of the PTEN gene, which acts as a natural brake on cell growth. When this brake fails, cancer cells can advance uncontrollably.
Knowledge accumulated over recent decades has suggested that PTEN could be used as a marker for clinical and therapeutic decision-making, but its clinical implementation has not been straightforward. Although PTEN loss is very common, measuring only the presence or absence of the protein does not always help predict how the tumor will evolve. This is because PTEN is regulated in very complex ways within the cell and can be lost or modified at different levels.
To overcome these limitations, researchers at CIC bioGUNE conducted an integrative study combining protein analysis with the study of the activity of thousands of tumor genes, applying advanced computational analyses to interpret the data. For this purpose, they created a cohort of prostate cancer cases with in-depth clinical, pathological, and molecular characterization in collaboration with the University Hospital of Basurto.
In addition, the team validated their results in a mouse model designed to study PTEN loss in prostate cancer development, which allowed them to demonstrate causally that the observed changes are a direct consequence of the gene’s absence.
The results revealed that when a tumor loses this protein, it sends signals that alter the surrounding normal tissue, changing its organization and behavior. This phenomenon, known as stromal remodeling, contains highly valuable information about how the disease will progress.
“What is particularly relevant is that the response of the tissue surrounding the tumor acts as a mirror of the cancer’s behavior,” explain CIC bioGUNE’s researchers. “Thanks to this biological signature, we can distinguish PTEN-deficient tumors that will remain indolent from those that may progress aggressively”.
This work paves the way for improving the classification of prostate tumors from the very moment of diagnosis, providing key information for clinical decision-making.
The study has been made possible thanks to CIC bioGUNE’s research ecosystem, member of BRTA, the collaboration of clinical teams from Basurto and Cruces in Bizkaia, and support from European programs ITN (PIPGen Project), Ikerbasque (Basque Foundation for Science), and the Cancer CIBER (CIBERONC).
Reference: Ivana Rondon-Lorefice, Jose I. Lopez, Aitziber Ugalde-Olano, Maite Zufiaurre, Ianire Astobiza, Natalia Martin-Martin, Laura Bozal-Basterra, Saioa Garcia-Longarte, Amaia Zabala-Letona, Sofia Rey, Aida Santos-Martin, Miguel Unda, Ana Loizaga-Iriarte, Mariona Graupera, Paolo Nuciforo, Arkaitz Carracedo and Isabel Mendizabal. Transcriptional network analysis of PTEN-protein-deficient prostate tumors reveals robust stromal reprogramming and signs of senescent paracrine communication. Molecular Oncology. DOI: 10.1002/1878-0261.70164.
About CIC bioGUNE
The Centre for Cooperative Research in Biosciences (CIC bioGUNE), member of the Basque Research & Technology Alliance (BRTA), located in the Bizkaia Technology Park, is a biomedical research organisation conducting cutting-edge research at the interface between structural, molecular and cell biology, with a particular focus on generating knowledge on the molecular bases of disease, for use in the development of new diagnostic methods and advanced therapies.
About Ikerbasque
Ikerbasque - Basque Foundation for Science - is the result of an initiative of the Department of Education of the Basque Government that aims to reinforce the commitment to scientific research by attracting, recovering and consolidating excellent researchers from all over the world. Currently, it is a consolidated organization that has 290 researchers/s, who develop their work in all fields of knowledge.
About BRTA
BRTA is an alliance of 4 collaborative research centres (CIC bioGUNE, CIC nanoGUNE, CIC biomaGUNE y CIC energiGUNE) and 13 technology centres (Azterlan, Azti, Ceit, Cidetec, Gaiker, Ideko, Ikerlan, Leartiker, Lortek, Neiker, Tecnalia, Tekniker y Vicomtech) with the main objective of developing advanced technological solutions for the Basque corporate fabric.
With the support of the Basque Government, the SPRI Group and the Provincial Councils of the three territories, the alliance seeks to promote collaboration between the research centres, strengthen the conditions to generate and transfer knowledge to companies, contributing to their competitiveness and outspreading the Basque scientific-technological capacity abroad.
BRTA has a workforce of 3,500 professionals, executes 22 % of the Basque Country's R&D investment, registers an annual turnover of more than 300 million euros and generates 100 European and international patents per year.
See a large version of the first picture