Barbara Hernando
“What surprised us most was the sheer scale of the damage coming from inside the cell,” says Barbara Hernando, a researcher at the CNIO and one of the study’s four joint first authors. “We looked for the marks that tobacco, sunlight and other external agents leave on DNA, the way you can read them in lung or skin cancer. Across almost a thousand genomes, we found practically none.” That does not mean environmental exposures or lifestyle are irrelevant to prostate cancer. “Diet, weight and inflammation can all influence whether prostate cancer develops without leaving any trace in the DNA,” Hernando adds.
The work brings the prospect of reliable prognostic markers closer. The analysis showed, for instance, that when one particular faulty process was the most active, the cancer was more likely to spread. That pattern held after taking into account age, tumour stage and the grade a pathologist assigns to a tumour under the microscope.
The team was also able to link one active process to a small group of patients who responded better to a specific type of therapy. That finding came from 25 men, and was examined after the fact rather than in a trial designed to test it.
These results offer clues that could help stratify patients and personalise treatment – but not yet. “Before this reaches a hospital, the findings have to be confirmed in other groups of patients,” says Macintyre. “The measurement then has to become a test that gives the same answer every time. That test has to be trialled in men who are making real decisions about their treatment. And it has to be shown to help them.”
“We have created a map of the biological processes that drive prostate cancer,” says Joachim Weischenfeldt, professor at the Biotech Research and Innovation Centre of the University of Copenhagen and Rigshospitalet, who co-led the study. “It is not going to change how any man is treated tomorrow. But it runs on the kind of DNA sequencing that several health systems already carry out for cancer patients. What we are proposing is to read existing data differently, not to build a new test from scratch.”
Source: Centro Nacional de Investigaciones Oncológicas (CNIO)