The ICR’s focus on the deadly male cancer is paying off
Prostate cancer is the most common cancer in men in the UK. More than 35,000 men are diagnosed with the disease annually, and for 10,000 men a year it proves fatal. Yet despite this terrible toll, prostate cancer has historically not attracted the funding or research attention given to other tumours. In 2001, this started to change with the opening of the Everyman Centre at the ICR, Europe’s first and only dedicated male cancer research centre. Medical research can be a slow process, but the past decade of intensive work into prostate cancer is happily now starting to pay off.
In the final months of 2010, ICR scientists published four major studies that have the potential to significantly improve the lives of men with prostate cancer. These publications reflect the ICR’s focus on both developing treatments and finding new tests to improve screening and diagnosis for this disease.
Treating prostate cancer
Until recently, men with advanced prostate cancer had few treatment options. Standard treatment involved hormone therapy followed by the chemotherapy drug docetaxel - however over time most men’s cancer would develop resistance to these therapies and would often prove fatal. Other treatments could be given to reduce pain, but no others had been shown to extend life.
Professor Johann de Bono, who leads the Prostate Cancer Team in the ICR’sSection of Medicine, says there was a “major unmet medical need” to find new drugs for these men. Professor de Bono has taken a number of prostate cancer drugs to trial stage, including leading Phase III trials of two drugs that have recently been found to extend life for men with advanced prostate cancer. The regulators have not yet approved the drugs for use in the UK, but there is the possibility they could soon be administered to patients one after the other and could give men significantly more time.
New chemotherapy drug cabazitaxel
The first of these drugs, cabazitaxel, is a chemotherapeutic agent that has already been approved by the US Food and Drug Administration (FDA) for use in combination with the steroid prednisone - largely on the basis of these trial results.
Cabazitaxel was tested in men with metastatic advanced prostate cancer who had developed resistance to hormone treatment and docetaxel. Men were given prednisone with either cabazitaxel or mitoxantrone, a chemotherapy drug that can improve patient’s quality of life but has not been shown to prolong life.
The study, known as TROPIC and funded by sanofi-aventis, was conducted in 146 trial sites in 26 countries around the world. The results showed that cabazitaxel blocked cancer growth for twice as long as mitoxantrone (1.4 months compared to 2.8 months), and men’s levels of prostate specific antigen (PSA), the standard measure of tumour activity, stayed down for longer.
New hormone treatment abiraterone
The second drug, abiraterone, was discovered at the ICR, which also led Phase I, II and III trials testing the drug’s safety and effectiveness in patients. Results were recently announced for the Phase III trial, which involved almost 1,200 men from 147 hospitals in 13 countries.
The average overall survival among the 797 patients who received abiraterone acetate plus the steroid prednisone was 14.8 months, compared to 10.9 months for the 398 patients who received the steroid and a placebo. Doctors also reported patients taking abiraterone acetate generally did not experience some of the unpleasant side-effects associated with chemotherapy.
“This drug improves not only quality of life but survival and very few drugs have done that before, so it’s really quite an important development,” Professor de Bono says.
Abiraterone, which is licensed from BTG International LTD to Janssen, has also led to a greater understanding about the way prostate cancer develops.
“Prostate cancer is fuelled by testosterone and it now appears that prostate cancer cells can produce this male hormone themselves. Abiraterone targets the pathways involved in the production of testosterone, and stops it being produced in the testes, the adrenal gland and the prostate tumours themselves,” explains Professor de Bono.
Detecting prostate cancer
Patients generally have a much better prognosis when cancers are diagnosed at the early stage. So as well as developing new treatments for prostate cancer, ICR scientists are also investigating ways to improve detection and monitor progression of the disease. Professor Ros Eeles from the ICR and The Royal Marsden and her colleagues have found two potential biological indicators of the risk of prostate cancer – a protein present in urine, and the relative length of men’s fingers. These biomarkers could be used to identify men at higher risk of prostate cancer, who could then be targeted for screening.
Urine test for prostate cancer
One of the new studies builds on genetic discoveries made by Professor Eeles and her team, after they compared the genome of thousands of men both with and without prostate cancer to find genetic changes more common to sufferers. This technique, called a genome wide association study, identified a number of variations in the DNA code that gave an increased risk of developing prostate cancer. One of the common changes, occurring in around 30-40 per cent of European men, is located in the section of DNA that ‘switches on’ the production of a protein called microseminoprotein-beta (MSMB).
In one of the latest studies, scientists from the Cancer Research UK Cambridge Research Institute and the ICR measured the level of MSMB protein in the urine of 350 men with and without prostate cancer, and also tested them for the associated genetic change. They found that the genetic change in the MSMB gene was significantly associated with a reduction in the amount of MBMB protein present in urine.
Men’s level of MSMB protein would be easy to measure as it is present in urine, raising the possibility of a simple urine test that could to identify men at greater risk of developing prostate cancer. It could also potentially be used alongside PSA testing to improve detection of prostate cancer and for monitoring progression of disease.
Finger length linked to prostate cancer risk
The second study found a risk factor that would be even easier to measure: men’s finger length. Researchers at the ICR and the University of Warwick found men whose index finger is longer than their ring finger were one third less likely to develop the disease than men with the opposite finger length pattern.
Over a 15 year period from 1994 to 2009, the researchers quizzed more than 1,500 prostate cancer patients along with more than 3,000 healthy control cases. The men were shown a series of pictures of different finger length patterns and asked to identify the one most similar to their own right hand.
The most common finger length pattern, seen in more than half the men in the study, was a shorter index than ring finger. Men whose index and ring fingers were the same length (about 19 per cent) had a similar prostate cancer risk, but men whose index fingers were longer than their ring finger were 33 per cent less likely to have prostate cancer. Risk reduction was even greater in men aged under 60 years– these men were 87 per cent less likely to be in the prostate cancer group.
The relative length of index and ring fingers is set before birth, and is thought to relate to the levels of sex hormones the baby is exposed to in the womb. Less testosterone equates to a longer index finger; the researchers now believe that being exposed to less testosterone before birth helps protect against prostate cancer later in life.
Professor Eeles said: “At the moment, PSA testing is the best method we have to detect prostate cancer but it has significant limitations, so there is an urgent need to find new biomarkers such as MSMB and relative finger length that could be used in screening and diagnosis. We are very excited that there may be simple tests for people at higher risk of prostate cancer.”
The ICR’s vision is that one day people may live their lives free from the fear of cancer as a life threatening disease. With these recent successes in prostate cancer, a major step has been taken in the right direction.