Prostate cancer: entering a golden age of research

Although there have been big advances in prevention, diagnosis and early treatment of prostate cancer over the past 20 years, until recently there was a huge gap in treatment once the disease turned aggressive. For many years, the only effective treatment for men with advanced prostate cancer who had become resistant to standard hormone therapies was the chemotherapy agent docetaxel, and palliative therapies that managed pain.

But oncologists are now hailing this as the ‘golden age of prostate cancer research’ after a whole series of new prostate cancer drugs reached the clinic. The ICR, alongside its hospital partner The Royal Marsden NHS Foundation Trust, has played a major role in developing four of the five new drugs to have been shown in later-phase trials to extend life for men with advanced prostate cancer. One of the most successful of those – abiraterone – was discovered here at The Institute of Cancer Research, London – the others being radium-233 chloride, cabazitaxel and now enzalutamide.

Key to these developments is Professor Johann de Bono, Professor of Experimental Cancer Medicine at the ICR and Honorary Consultant at The Royal Marsden. And the fruits of the recent advances in prostate cancer treatment are really beginning to show. A study conducted at The Royal Marsden by Professor de Bono and colleagues has shown that patients with advanced prostate cancer treated with either docetaxel, abiraterone, enzalutamide, cabazitaxel and radium were living with the disease on average for more than twice as long as a decade ago. Professor de Bono says: “A patient with incurable prostate cancer will now live for around three-and-a-half years – a huge improvement in outcome compared with 10 years ago for this most common of male cancers.”

As well as discovering new drugs, researchers are looking to repurpose drugs that have already been used in other cancers. Cabozantinib is a drug approved by the Food and Drug Administration in the US in November 2012 for the treatment of medullary thyroid cancer. It has now shown impressive results in men with advanced, treatment-resistant prostate cancer that has spread to their bones - whose disease was getting worse despite previous chemotherapy. Cabozantinib shrunk prostate tumours that had spread to the bones and helped to relieve bone pain. Men also reported that the cancer was interfering less with their daily life, including their ability to sleep and carry out normal activities. Professor de Bono says: “Although we have helped develop a number of new drugs for advanced prostate cancer over recent years, these tumours ultimately and invariably develop resistance to treatment and so finding new options for men with late-stage disease is still crucially important. As prostate cancer progresses, it most commonly spreads to the bones, which can lead to bone fractures and severe pain. Cabozantinib is showing promise in improving bone disease, decreasing complications from prostate cancer spread to bone, and also taking away the pain of bone spread, improving quality of life.”

One final mention should go to a drug called olaparib – a PARP inhibitor. Olaparib is one of the first successful examples of a new type of personalised medicine using ‘synthetic lethality’, in which a treatment takes advantages of weaknesses in cancer cells caused by their specific molecular defects. Patients with inherited forms of advanced breast, ovarian and prostate cancers – caused by mutations in the BRCA1 and BRCA2 genes – have been successfully treated with olaparib in small trials. Recent research has also shown that PARP inhibitors have anti-tumour activity against prostate cancers that are not inherited. Professor de Bono says: “We are now conducting a trial, called TO-PARP, evaluating these drugs’ anti-tumour activity against this disease. This trial is importantly evaluating the molecular signatures of tumour cells in responding and non-responding patients so we can clinically qualify biomarkers that can predict which prostate cancers respond to PARP inhibitor treatment. We hope to report on this trial later this year and are very hopeful that our analyses of the genomes of each patient on this trial will identify which types of prostate cancers respond to these orally available, and well-tolerated drugs.”

Over the last decade, there has been fantastic progress in the treatment of advance prostate cancer – much of which the ICR has helped to drive. Advanced prostate cancer is still incurable, but new treatments are giving men more time to do the things that matter to them with their loved ones.