Monday, 14 August 2017

Discovery of new prostate cancer biomarkers could improve precision therapy

Mayo Clinic researchers have identified a new cause of treatment resistance in prostate cancer. Their discovery also suggests ways to improve prostate cancer therapy. The findings appear in Nature Medicine.
In the publication, the authors explain the role of mutations in the SPOP gene on the development of resistance to one class of drugs. SPOP mutations are the most frequent genetic changes seen in primary prostate cancer. These mutations play a central role in the development of resistance to drugs called BET-inhibitors.
BET, bromodomain and extra-terminal domain, inhibitors are drugs that prevent the action of BET proteins. These proteins help guide the abnormal growth of cancer cells.
As a therapy, BET-inhibitors are promising, but drug resistance often develops, says Haojie Huang, Ph.D., senior author and a molecular biologist within Mayo Clinic's Center for Biomedical Discovery. Prostate cancer is among the most diagnosed malignancies in the United States. It is also the third leading cause of cancer death in American men, according to the American Cancer Society. Because of this, says Dr. Huang, improving treatments for prostate cancer is an important public health goal.
In the publication, the authors report SPOP mutations stabilize BET proteins against the action of BET-inhibitors. By this action, the mutations also promote cancer cell proliferation, invasion, and survival.
"These findings have important implications for prostate cancer treatment because SPOP mutation or elevated BET protein expression can now be used as biomarkers to improve the outcome of BET inhibitor-oriented therapy of prostate cancer with SPOP mutation or BET protein overexpression," says Dr. Huang. Mutations in the SPOP gene can then be used to guide administration of anticancer drugs in patients with prostate cancer: The Nature Medicine publication presents four major discoveries:
  • BET proteins (BRD2, BRD3, and BRD4) are true degradation substrates of SPOP.
  • SPOP mutations cause elevation of BET proteins in prostate cancer patient specimens.
  • Expression of SPOP mutants leads to BET-inhibitor resistance and activation the AKT-mTORC1 pathway that promotes cancer cell growth and survival.
  • Co-administration of AKT inhibitors overcomes BET inhibitor resistance in SPOP-mutated prostate cancer. Mayo Clinic Ventures, the technology commercialization arm of Mayo Clinic, has a patent application in place for this promising prostate cancer biomarker and therapeutic technology.

Story Source:
Materials provided by Mayo Clinic August 2017

Sunday, 6 August 2017

The robot that could cure your prostate cancer

A guide to the other advances helping win the war against this disease feared by men

     Thirty men a day in the UK die of prostate cancer. It is a gloomy statistic – yet talk to experts in the field and the mood is anything but pessimistic. In fact, there is a sense that science is on the verge of turning the disease from one to be feared to little more than a chronic illness controlled with drugs, like asthma or diabetes.

Survival rates are better than ever: the number of deaths keeps falling and ten years after diagnosis, 84 per cent of men are still alive.
From more accurate screening and less invasive diagnostic techniques to robotic surgery and targeted drugs, huge advances in treatments also mean men are more likely to be cured, and less likely to be left impotent or incontinent – the big worries for most.
Surgeon Christopher Ogden with the da Vinci Xi surgical robot that he uses to perform robotic prostatectomy at the Royal Marsden Hospital, London
Surgeon Christopher Ogden with the da Vinci Xi surgical robot that he uses to perform robotic prostatectomy at the Royal Marsden Hospital, London

‘Soon this could be a disease that men routinely survive, and has little impact on their daily life,’ says Dr Iain Frame, research director at the charity Prostate Cancer UK.
But with advances in therapies comes new information for every man with prostate cancer and his loved ones to absorb – much of it complex. We spoke to Britain’s foremost experts, who between them have treated tens of thousands of men, about the new developments every patient should be aware of and the treatments that really do make a difference…
Christopher Ogden is a surgeon at the Royal Marsden Hospital in London
Christopher Ogden is a surgeon at the Royal Marsden Hospital in London
Christopher Ogden, a surgeon at the Royal Marsden Hospital in London, pioneered the use of robotic surgery for prostate cancer – treating more than 2,500 men with a technique that revolutionised the treatment of the disease. 
He says: ‘Although surgery might not be the first thing we offer men with prostate cancer, many will at some point need to have the gland removed. The operation is called a radical prostatectomy and it offers a cure in 95 per cent of cases.
‘Decades ago, the only option was open surgery – with the prostate removed through a long incision below the navel. Then came keyhole surgery, where instruments and a camera were inserted though several tiny cuts in the abdomen.
‘About 13 years ago, I was the first British surgeon to use the Da Vinci robot, which is a high-tech version of keyhole surgery, where instruments are held by a machine with robotic arms.
‘Back then it was seen as a bit outlandish. Now it’s the gold standard in surgery, with nearly 100 robots in the country, and hundreds more surgeons trained to use them.
‘The arms are controlled by the surgeon from a console next to the operating table. The procedure eliminates the risk of surgical error through hand tremors or shakes. And the video display in the console is highly magnified, which means we are better at avoiding damage to nearby nerves.
‘This means the risk of the complication feared most by men, erectile dysfunction, may be reduced.
‘The robot performs at least twice as well as the best surgeon in getting all cancer out in one go – reducing the need for repeat surgery, and greater risk of erectile dysfunction and incontinence.’
Professor Roger Kirby is a consultant urologist and director of The Prostate Centre in London
Professor Roger Kirby is a consultant urologist and director of The Prostate Centre in London
Professor Roger Kirby, consultant urologist and director of The Prostate Centre in London, is a leading light in the field, having published more than 300 scientific papers on prostate tumours. He says:
‘Today, two-thirds of men with prostate cancer will never need to have surgery, and can instead undergo active surveillance – where regular checks are carried out to see if the tumour is progressing. If the cancer remains small and slow-growing, then there is no reason to operate.
‘Last year a study that tracked 1,600 men with prostate cancer for ten years found no difference in survival rates between men who had active surveillance, surgery or radiotherapy.
‘If they do need treatment, there are several options before surgery. Prostate tumours are very sensitive to testosterone, so we give men powerful hormone-blocking drugs which slow down cancer growth.
‘High-Intensity Focused Ultrasound [HIFU] – where a targeted blast of ultrasound is fired at the cancerous part of the prostate – destroys the tumour by heating it but leaves the rest of the prostate intact. But it's only offered on the NHS in clinical trials, and more research is needed before it can be more widely used.
‘Radiotherapy and chemotherapy also remain important treatment options – but robotic surgery may mean less so in the future.’
Nicholas James is Professor of Clinical Oncology at the Institute of Cancer and Genomic Sciences at the University of Birmingham
Nicholas James is Professor of Clinical Oncology at the Institute of Cancer and Genomic Sciences at the University of Birmingham
Nicholas James is Professor of Clinical Oncology at the Institute of Cancer and Genomic Sciences at the University of Birmingham, and chief investigator of the huge Cancer Research UK-funded STAMPEDE trial into treating aggressive prostate cancer. He says:
‘Prostate cancer is often in the news with stories of new drug developments, treatments, and tests. However, until a therapy is approved for use in the NHS, often the only way to access it is via a clinical trial.
‘I recommend men get themselves on to one if they can, and there are many being run by the NHS right now.
‘In a trial, all treatment must be done to impeccable standards to ensure the quality of the data.
‘This means that even patients who aren’t receiving the “new” drug or whatever is on trial still get a gold-standard level of quality when it comes to treatment.
‘If you are told there is a trial that isn’t suitable for you at the moment, then fine, but if your hospital simply doesn’t run trials, then I would try to look elsewhere for treatment. It is a badge of quality if a hospital is actively engaged in clinical trials.
‘One of the biggest recent treatment breakthroughs was discovered in the Cancer Research UK-funded STAMPEDE trial that I led.
‘There is also growing evidence from another British trial that doing an MRI of the prostate might spare some men the ordeal of a biopsy.
‘The scans also enable us to keep monitoring the patient more safely without them having to have a needle inserted into the prostate.
‘This means surveillance becomes safer, and more men will be able to avoid radiotherapy and surgery – in some cases totally, others for as long as possible.’
Dr Iain Frame is research director for the charity Prostate Cancer UK
Dr Iain Frame is research director for the charity Prostate Cancer UK
Dr Iain Frame, research director for the charity Prostate Cancer UK, describes it's ambitious’ ten-year plan to halve mortality and bolster survival through better diagnosis and new treatments. He says:
‘Our main goal is to improve diagnoses, which will cut death rates by picking up cancers at an earlier stage. At the moment we are not very good at differentiating very aggressive tumours from the slow-growing ones that may never cause a problem.
‘So we are funding research looking at ways to tell them apart – in cancer blood tests that have been dubbed liquid biopsies.
‘Most middle-aged men will be familiar with prostate specific antigen or PSA testing. The newer tests being researched look for genetic material and other compounds in the blood that are produced by tumours, and can tell us about the cancer without us actually having to take solid samples.
‘Last year, we drew up a ten-year plan which has a key objective of halving halve the number of deaths to about 7,000 a year by 2026, and better diagnosis will help make this a reality. We think it is ambitious but achievable.’
Rock drummer Kenney Jones has played in The Faces and The Who 
Rock drummer Kenney Jones has played in The Faces and The Who 
Rock drummer Kenney Jones, 68, of iconic bands The Faces and The Who, was diagnosed in 2013. The father- of six, who lives in Surrey with wife Jayne, 59, is now cancer-free. He says:
‘I am passionate about talking about prostate cancer because I want men to catch it early, giving them a better chance of survival.
‘I was incredibly lucky to have been caught at the “late” end of early. The disease was still contained inside the prostate.
‘But looking back, I’d had symptoms for years. I blamed getting up two or three times a night on having a few glasses of wine in the evening. I also ignored the fact that my urine flow had slowed down.
‘I was offered a PSA test, a blood test that can detect problems with the prostate, while at my GP surgery for something else. I’d never heard of this test, but it saved my life. Just over a week later I was diagnosed with prostate cancer and discussing treatment options.
‘My biggest worry was whether the cancer had spread. Thankfully, it hadn’t – and I was offered brachytherapy, a type of radiotherapy.
‘This involved having 80 tiny titanium pellets inserted into my prostate to kill the tumour. They blast away at it for a few months and once they’ve done their job, they become inert and remain inside.
‘There were side effects – the radioactivity causes the prostate, bladder and the whole area to become inflamed. I couldn’t pee. It all calmed down after a few months and it worked. I am cancer-free and everything down there works fine.
‘All men need to talk about prostate cancer. It’s a killer – I lost my friend Alvin Stardust to it because he was diagnosed so late.
‘I have also warned my four sons to be vigilant – there were many men younger than me in hospital when I was there. This disease doesn’t discriminate.’

Don't fear THAT won't hurt! 

By Dr Ellie Cannon  
Q) Does a test still involve THAT rather intimate examination?
A) A digital rectal examination is the normal way for a GP or specialist to examine a prostate. The gland is located in the pelvis, below the bladder, and can be examined by placing a finger into the rectum. It’s really not painful, and we do it all the time so you shouldn’t be embarrassed. The doctor can feel whether the prostate feels hard and irregular, which may be a sign of cancer. Urinary tract symptoms can also signal many far more common benign conditions, so an examination is an important way to distinguish between these.
Q) Is there anything I can do to reduce my risk?
A) Unlike other cancers, there are no ‘modifiable’ risk factors for prostate cancer – ones that you can improve yourself through lifestyle changes such as diet. It’s why screening tests and awareness is so important.
Q) If it’s not prostate cancer, what’s causing my symptoms?
A) You are far more likely to have a benign prostate condition than prostate cancer. Lower urinary tract symptoms such as waking at night to pass water, difficulties with flow and the increased need to go are common in men. These can be the signs of cancer but are also symptoms of benign prostate enlargement – a noncancerous condition treated with medication.
Q) Who needs to worry about prostate cancer?
A) A quarter of all new cancers in men are prostate, making it the most common male cancer – so really all men need to know about it. The average age of diagnosis is 72 and it is considered uncommon under the age of 50. Men from black Caribbean or African ancestry are at highest risk – and they are also more likely to have a more aggressive cancer. Your risk is increased by 2.5 times if your father had it.

Daily Mail publication August 2017