20 Nov 2014

Earlier this month the UK’s biggest gathering of cancer experts took place in Liverpool – the NCRI cancer conference. We sponsored a session and went along to represent the organisation, meet experts and hear from the cutting edge of cancer research. But we also wanted to find out what other prostate cancer experts made of it.

Dr Hayley Whitaker is the lead scientist of the Biomarker Initiative at the Cambridge Cancer Centre. And she’s fast becoming a leader in the field of prostate cancer biomarker discovery. We’ve been working with Dr Whitaker for a while now and really admire her scientific ability, as well as her enthusiasm for spreading the R word (research)  to people who don’t have a science background. So we asked to keep her eye out for the hottest topics and most interesting discussions. Her report is this week’s guest blog.

Dr Hayley Whitaker

Dr Whitaker: “Professor Richard Marais, co-Director of the Belfast-Manchester Movember Centre of Excellence, chaired the tenth National Cancer Research Institute (NCRI) meeting. And it was probably the best one yet.

“In the last few years, there’s really been an explosion of information available about cancer genetics, from individual projects to sequence tumour DNA to the work of the International Cancer Genome Consortium (ICGC) – an international effort to understand the DNA sequence of 50 different tumours, including prostate cancer, and how they’re translated into cell behaviour. The DNA inside cancer cells is often different to the DNA inside normal cells and can give us important clues as to how the cancer survives and grows. So studying the sequence of tumour DNA can help us spot those differences.

“This year, the NCRI meeting addressed some of the questions the whole cancer research community is asking such as: how do we use this data to best improve patient care? Many research groups are now using information like this to see how tumour DNA changes during treatment, and what that means for how well the patients will respond to the medication. These DNA changes are really important because as Professor Tim Maughan (Oxford) said, in reference to how quickly cancer cells can evolve, ‘It took us nine years to invent the drug and it took cancer nine weeks to work out how to beat it’. That quote has been called the best truism of the conference.

“And nowadays we don’t even need to go right into the depths of the tumour to find out how its DNA changes during treatment. Professor Caroline Dive (lead researcher in the Belfast-Manchester Movember Centre of Excellence) led a session where the speakers showed how they could find and track changes to tumour DNA circulating in the blood using a simple blood test. This offers a fantastic opportunity to monitor disease without invasive tests, but there may be extra technical challenges to using this system in prostate cancer patients. This is because prostate tumours release less DNA and fewer tumour cells into the blood compared to lung and colon tumours where much of the pioneering work was done.

“Professor Johann de Bono (Director of the London Movember Centre of Excellence, based at the Institute of Cancer Research) is using tumour cells circulating in the blood to monitor response to prostate cancer treatment. He reported on the early findings of the olaparib clinical trial for treating men with advanced prostate cancer. At this stage of the disease the mechanisms that normally repair DNA when it gets damaged become less efficient or stop working altogether. Olaparib is one of a class of drugs called PARP inhibitors, which target cancer cells with increased DNA damage and kill them. Overall patient responses to olaparib treatment have been very promising, with some patients showing complete removal of tumour cells in their blood. The team are now working to determine which patients are likely to benefit from olaparib treatment by sequencing the mutations found in their DNA.

“The role of DNA damage in advanced disease was a key theme in the prostate cancer talks, with Professor Karen Knudsen (Philadelphia, USA) presenting a comprehensive study on DNAPK. DNAPK is a protein that links signalling through the androgen receptor (a key driver of prostate cancer growth) to mechanisms for repairing damaged DNA. Dr James Knight (Oxford) also presented promising work on a new way of detecting damaged DNA that could one day be used in patients with advanced prostate cancer to tell when their DNA becomes damaged. This would allow them to be treated at the right time with the right drug, such as olaparib.

“With the big move toward grouping tumours according to their genetic and molecular information, there was also a clear message that we should be careful not to throw the baby out with the bathwater by forgetting what so-called ‘cancer stem cells’ (which are believed to be the first cells in a cancer), can tell us. Professor Luis Parada (Dallas, USA) demonstrated that in a disease called glioblastoma multiforme, ‘cancer stem cells’ may be important for treating cancers effectively.

“There are many groups working on prostate cancer stem cells too, not least Professor Norman Maitland (York). At the moment we tend to focus on removing the bulk of a cancer and detecting the genetic changes in these numerous cells, whereas Professor Parada suggested that it might be important to focus more efforts on identifying the genetic changes in the small number of cancer stem cells. This would mean we can kill these cells too and stop the cancer from re-growing after treatment.

“In a later session, Professor Manuel Salto-Tallez (Researcher in the Belfast-Manchester Movember Centre of Excellence, based at Queen’s University Belfast) gave an inspirational talk. He discussed how to routinely combine information about cancer genetics with clinical reports and results from biopsy samples to identify patients with the most aggressive colon and prostate cancers. This is exciting work that needs to be tested further in a study across multiple hospitals, but it signals the future direction for better prostate cancer diagnosis and better patient care.

“By the end of the meeting the organisers were asking for suggestions for topics for next year. Key debates on circulating tumour cells versus circulating DNA and how best to get to the bottom of all the information we now have available about different cancer types still remained hot favourites. This reflects the topics where research is continuing at a rapid pace. All of this bodes particularly well for prostate cancer where there are still big questions around diagnosis of aggressive disease and monitoring disease during treatment that need further research.”

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