Nav: Home

Gene testing could identify men with prostate cancer who may benefit from immunotherapy

June 14, 2018

Scientists have identified a pattern of genetic changes that could pick out men with advanced prostate cancer who are likely to benefit from immunotherapy.

Developing a genetic test to pick out these men could speed up the path of immunotherapy into use for prostate cancer patients.

A major clinical trial earlier this month became the first to show that immunotherapy could work in advanced prostate cancer - but only for about 10 per cent of men.

Now the new study, involving scientists at The Institute of Cancer Research, London, has discovered that testing the genetics of prostate tumours could identify the likely responders.

The research, published today (Thursday) in the prestigious journal Cell, found that men whose tumours had a distinct pattern of genetic changes could be much more likely to benefit from immunotherapy than otherwise.

The study was supported by funders including the Prostate Cancer Foundation and Stand Up 2 Cancer.

Scientists at The Institute of Cancer Research (ICR) worked with colleagues at the University of Michigan in the US to analyse tumour DNA collected internationally from 360 men with advanced prostate cancer that had spread.

They found that the tumours of 7 per cent of these men were missing both copies of a gene called CDK12, a trait that was linked with a unique pattern of additional genetic changes.

Tumours with this genetic profile contained a higher number of immune cells than other forms of advanced prostate cancer.

They also had a higher number of protein fragments on their surface, called neoantigens, which flag tumour cells to the immune system. Tumours that are associated with large numbers of immune cells and neoantigens often respond better to immunotherapy, presumably because the immune system has already begun to recognise elements of the cancer as foreign.

In a small pilot clinical study carried out in the US as part of the research, two out of four men with advanced prostate cancer whose tumours had CDK12-linked genetic changes responded remarkably well to the immunotherapy drug pembrolizumab.

It follows the results of a clinical trial led by the ICR and The Royal Marsden NHS Foundation Trust which showed pembrolizumab could benefit a subset of patients with advanced prostate cancer who had run out of existing treatment options.

In the new study, the pattern of genetic changes linked with the missing copies of the CDK12 gene was distinct from other, previously identified genetic subtypes of prostate cancer, making this an entirely separate form of the disease.

If the research can be replicated in larger numbers of patients, it could lead to introduction of a genetic test as a precursor to offering immunotherapy.

In future, CDK12 could also be explored as a genetic weakness that could be targeted by new precision drugs for prostate cancer. Professor Johann de Bono, Regius Professor of Cancer Research at The Institute of Cancer Research, London, said:

"Immunotherapy works for a relatively small group of men with advanced prostate cancer - but when it works, it really works. If we can identify in advance who will benefit, then it should accelerate the passage of immunotherapy into routine use for patients.

"Our new study has revealed a distinct group of men with advanced prostate cancer whose tumours have biological features that could make them likely to respond to immunotherapy drugs such as pembrolizumab.

"We now need larger clinical studies to further study the benefit of immunotherapy in this group of patients. In the future, a genetic test could help pick out men with this particular set of genetic changes, so that they can be considered for immunotherapy."

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

"Increasing our understanding of the biological and genetic features of cancer is vital in the search for smarter, kinder cancer treatments.

"It's exciting that this study may have cracked the underlying biology of why only some men with prostate cancer appear to respond well to immunotherapy.

"I look forward to this work being taken forward as soon as possible with the aim of ensuring that some men with prostate cancer can start having the same kinds of benefit from immunotherapy that we are seeing in other tumour types."

Howard Soule, Ph.D., executive vice president and chief science officer of the Prostate Cancer Foundation, said:

"The identification of CDK12 loss as a possible biomarker for identifying prostate cancer patients who may respond to checkpoint immunotherapy is a hugely significant finding, as researchers have struggled with how to effectively use immunotherapy in prostate cancer for many years.
-end-
"The Prostate Cancer Foundation is proud to have funded this foundational study."

Notes to editors

For more information please contact Sarah Wells in the ICR press office on 020 7153 5582 or sarah.wells@icr.ac.uk. For enquiries out of hours, please call 07595 963 613. The Institute of Cancer Research, London, is one of the world's most influential cancer research organisations.

Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden NHS Foundation Trust and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four centres for cancer research and treatment globally.

The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it is a world leader at identifying cancer-related genes and discovering new targeted drugs for personalised cancer treatment.

A college of the University of London, the ICR is the UK's top-ranked academic institution for research quality, and provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.

The ICR's mission is to make the discoveries that defeat cancer. For more information visit http://www.icr.ac.uk

Institute of Cancer Research

Related Prostate Cancer Articles:

First prostate cancer therapy to target genes delays cancer progression
For the first time, prostate cancer has been treated based on the genetic makeup of the cancer, resulting in delayed disease progression, delayed time to pain progression, and potentially extending lives in patients with advanced, metastatic prostate cancer, reports a large phase 3 trial.
Men taking medications for enlarged prostate face delays in prostate cancer diagnosis
University of California San Diego School of Medicine researchers report that men treated with medications for benign prostatic hyperplasia (enlarged prostate) experienced a two-year delay in diagnosis of their prostate cancer and were twice as likely to have advanced disease upon diagnosis.
CNIO researchers confirm links between aggressive prostate cancer and hereditary breast cancer
The study has potential implications for families with members suffering from these types of tumours who are at an increased risk of developing cancer.
Distinguishing fatal prostate cancer from 'manageable' cancer now possible
Scientists at the University of York have found a way of distinguishing between fatal prostate cancer and manageable cancer, which could reduce unnecessary surgeries and radiotherapy.
Researchers find prostate cancer drug byproduct can fuel cancer cells
A genetic anomaly in certain men with prostate cancer may impact their response to common drugs used to treat the disease, according to new research at Cleveland Clinic.
More Prostate Cancer News and Prostate Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...