Chasing cancer into a blind alley, the CRISPR craze, and the ‘nuisance’ placebo: our second update of highlights from the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool.

Friday 10 November 2017      Research blog
Visitors at the NCRI Conference in Liverpool

We’re excited to bring you the latest developments from this year’s conference, where the cancer research community gathered to share their progress and debate the best ways forward to prevent, detect and treat cancer, and improve the lives of everyone affected.

Cutting off cancer’s DNA repair routes

During the conference both Prof Steve Jackson from the University of Cambridge and Breast Cancer Now researcher Prof Chris Lord expressed their view that how a cell responds to damaged DNA was “arguably the most important topic in cancer science”.

Our DNA has evolved to be a safe haven for all our genetic information, but it’s being bombarded constantly by the outside world. Our cells are therefore specially equipped to deal with lots of DNA damage on a daily basis, and these repair processes play a big role in protecting us against cancer. Mutations in these proteins, therefore, often lead to cancer, and many treatments aim to damage cancer’s DNA even further, to the extent that it can’t be repaired, and the cancer cells have no choice but to die.

One DNA repair protein that has become an important focus in cancer biology is PARP. Prof Jackson described PARP as a “molecular policeman”, searching the cell for DNA damage and raising the alarm if it finds any. PARP repairs damaged DNA alongside the BRCA2 protein, but if the cell has a BRCA mutation, PARP has to work alone.

As we’ve highlighted before, Breast Cancer Now scientists helped to make the discovery in 2005 that by stopping PARP from doing its job in cancer cells with mutated BRCA2, the cell is no longer able to stay alive. Since then, drugs that inhibit PARP have become exciting new treatments that are now available for patients with BRCA-mutated ovarian cancers, and recently showed exciting results in clinical trials for treating BRCA-mutated breast cancer.

In another session, Dr Alan D’Andrea explained how tumour cells being treated with PARP inhibitors are finding ways to become resistant to them so they can survive. Cells have a choice of different ways they can do this, which means finding out the pathways involved, and how a cell decides which one to use, is vital in stopping resistance. Both Dr D’Andrea and Prof Jackson have found proteins that might be helping cancers to resist PARP inhibitors, which could lead to new drugs which work alongside PARP inhibitors, or destroy the cancer cells despite PARP inhibitors no longer working. Prof Jackson ended by making the point that coming up with new drugs that can “chase cancer into a blind alley” is what’s needed to head off resistance.

The CRISPR craze

The final day began with the exciting potential of gene editing to study and even treat cancer. The idea is simple; editing a cell’s DNA can ultimately increase or decrease the amount of certain proteins the cell manufactures, which might be driving or blocking cancer. Gene editing is being used increasingly to create models of cancer to study in the lab, and to add markers to genes of interest so scientists can monitor them inside a cell.

One technology used to edit genes is ‘CRISPR-Cas9’, which has been taking the medical science world by storm. Prof Jacqueline Boultwood from the University of Oxford introduced the session with some recent news headlines about this new and exciting tool, referring to its popularity as ‘the CRISPR craze’.

Speakers in the session had used CRISPR-Cas9 to create white blood cells that produce interferon – a treatment for leukaemia – that when put back into a patient’s blood are drawn to tumours and allow the drug to take effect. We also heard how CRISPR-Cas9 is being used to search the genome of acute myeloid leukaemia cells to find genes that might be druggable.

The potential uses of this technique across cancer research could be far-reaching, and based on what we heard, deserves the hype it’s been getting.

Embracing the ‘nuisance’ placebo effect

While much of conference focussed on finding more effective ways to treat cancer, importantly we also heard from experts helping people with cancer to have the best possible quality of life after their diagnosis. Speaking about the best ways to manage bone pain, a common complication arising from cancer, Prof Mike Bennett from the University of Leeds explained that paying attention to patients’ needs is crucial. For instance, some people might prefer to tolerate a certain amount of pain if it means they can avoid the side effects of pain relief treatments which could make it difficult to concentrate or exercise, for example. Interestingly he reported that the more patients were told about the benefits of pain relief treatments, and about how to manage their pain, the more they experienced better pain control.

Prof Marie Fallon of the University of Edinburgh agreed that “we can’t underestimate the role of patient expectations”. Speaking about clinical trials of pain control, she argued that while the placebo effect has been considered a ‘nuisance’ that muddies results, it also has the potential to give us invaluable insight into the biological, cognitive and emotional factors that make patients feel better. To un-muddy the waters in these trials, she has developed a trial design which identifies patients experiencing a strong placebo effect at the beginning of the study, and then re-randomises these patients so their responses can be studied in more detail.

More information

Catch up on our first instalment of highlights from the conference. You can also follow the latest from the conference on Twitter using the hashtag #NCRI2017.