Hypoxia related mRNA biomarker to predict biochemical failure and metastasis for prostate cancer

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Published: 8 Feb 2018
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Dr Ananya Choudhury - The Christie NHS Foundation Trust, Manchester, UK

Dr Choudhury speaks with ecancer at the 2018 ASCO Genitourinary Cancers Symposium about the challenges faced when attempting to select patients who have a poor prognosis.

She goes on to discuss a study looking into the use of a hypoxia related mRNA biomarker to predict biochemical failure and metastasis for prostate cancer.

One of the biggest challenges we have for prostate cancer is selecting the patients who don't do well. Prostate cancer compared to lots of other cancers, some would say, has a reasonable prognosis and we know that we're improving survival rates all the time but there's still a proportion of patients who, despite our best efforts, don't respond well to treatment and will die of their prostate cancer. What we wanted to do is we wanted to try and devise a test that would select the patients out who might need further treatment or more intensified treatment in the future.

We had access to a number of different cohorts of patients who had been treated with radiotherapy and their original biopsy blocks. So we came up with the hypothesis that if we could extract RNA from those biopsy blocks then we might be able to find RNA markers that selected the patients who did less well. Initially what we did is we took four different prostate cancer cell lines and we exposed them to different levels of oxygen in vitro and we looked at the changes in RNA expression across these four cell lines as we decreased the amount of oxygen the cells were growing in. What we found was we found that different genes were activated as the oxygen levels lowered and we know historically that prostate cancers that have low oxygen levels actually have a poorer prognosis. So we took these genes and made a signature out of them, so a particular pattern, and then we looked to see if we could find this pattern in RNA extracted from the tissue blocks from the patients treated with radiotherapy.

What our research shows is using an RNA genomic signature we can stratify patients into patients who do well versus patients who do poorly using the signature and therefore we can select the patients who do less well. The cohorts that we have used to date have been predominantly patients who have been treated with surgery. The next stage of the project is to look at patients who have been treated with radiotherapy and see if we can still stratify patients. If we can, the long-term goal is to see if we can devise a clinical trial using the biomarker signature that we have to select patients who need more intensified treatment and we actually may be able to treat them with a treatment that targets low oxygen levels.

What benefit might this have on patients in the future?

My hope is that for patients in the future if our work pans out the way we'd like it to that we will be able to do a biopsy on a patient with prostate cancer, we'll be able to extract the RNA from that tissue, test the tissue with our signature and find out whether that patient has a low oxygen prostate cancer or a high oxygen prostate cancer. If the patient has a low oxygen prostate cancer then my hope would be to be able to treat that patient with radiotherapy and hormone treatment, which is standard now, but also add in a treatment that would improve the oxygenation of the cancer while we're giving radiotherapy and therefore improve the way the radiotherapy works.