Cancer cannot be understood as a single, uniform disease.

The more we delve into studying each type of tumour, the more we recognise the need to subclassify the disease.

This concept has led to what we now call precision oncology, characterising the molecular features of a patient's specific cancer to determine the most effective treatment.

Prostate cancer is considered the most prevalent tumour among men, and it typically has a high cure rate.

As such, although many men will be diagnosed with this cancer, the majority will be cured.

"However, when we refer to prostate cancer statistics, we are actually talking about 90% of patients," explains Carracedo, Ikerbasque Research Professor at CIC bioGUNE, member of BRTA.

He adds, "About 5–10% of men with prostate cancer present with metastasis at the time of diagnosis, and this variant of the disease behaves more aggressively than the others." In recent years, this form of the disease has begun to be studied separately to better understand it and improve its early diagnosis and treatment.

"Prostate cancer that presents initially with metastasis is both a social and public health challenge, despite accounting for just 5% of diagnosed cases, it is responsible for 50% of prostate cancer-related deaths," notes Dr. Miguel Unda, who was Head of Urology at Hospital Universitario de Basurto when the study was conceived and is now an "ad honorem" researcher at IIS Biobizkaia.

In response to this challenge, CIC bioGUNE established a multidisciplinary, multi-regional team of basic, clinical, and computational researchers to molecularly catalogue this aggressive form of the disease.

The project began in 2018 with funding from the Asociación Española Contra el Cancer (AECC), involving the study of hundreds of samples using cutting-edge technologies.

Dr. Ana Loizaga, participating from Basurto University Hospital, explains that “a detailed analysis of this type of tumour required accessing tissue archives from the past 10 years at Basurto Hospital, in order to obtain a sample size robust enough for analysis. Moreover, we had to innovate within the clinical pathway to ensure that samples extracted from patients could be delivered to CIC bioGUNE within just a few hours.” Dr. Isabel Mendizabal, researcher supported by Ikerbasque and the Fundación Cris contra el Cáncer, co-led the study by advancing the computational approach that allows decomposition of tumours into their cellular components.

“Most molecular studies treat the tumour as a homogeneous tissue, which limits our understanding of the disease,” Mendizabal explains.

She continues, “In this study, we complemented that approach with new technologies that allow us to analyse each cancer component in isolation, like tasting each fruit in a smoothie individually, instead of guessing the ingredients.”

This study reveals that metastatic prostate cancer represents a biologically distinct entity.

The research team discovered that cancer cells in these tumours use a different "language" to communicate with normal cells, altering their behaviour in ways that benefit the tumour.

“We observed that the aggressiveness of this disease is partly due to how cancer cells 'educate' normal cells, through mechanisms we had not seen before,” Carracedo explains.

He continues, “The study we developed, through collaboration among prestigious institutions across Spain, lays the groundwork for future research that will help translate this knowledge into new clinical guidelines for managing this form of prostate cancer.”

The study was led by CIC bioGUNE in collaboration with Basurto University Hospital, Morales Meseguer Hospital in Murcia, and 12 de Octubre Hospital in Madrid, as well as research centres including IRB Barcelona, VHIO, and the Josep Carreras Institute, among others.

Dr. Carracedo leads a research group at the Spanish Biomedical Research Network in Oncology (CIBERONC).

Journal: Genome Biology

Source: CIC bioGUNE