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Hope for lung cancer, yeast, and re-purposing drugs: NCRI conference 2016

Walking down the stairs of my Liverpool hotel, a converted 19th century tobacco warehouse, the irony of the location struck me. I was on my way to the opening session of the annual National Cancer Research Institute (NCRI) Conference to hear the lecture given by Dr Charles Rudin, from the Memorial Sloan Kettering Cancer Centre, USA, on his work in lung cancer. This was particularly apt since November is lung cancer awareness month. I was on my way to join thousands of scientists, clinicians and people directly affected by cancer, who had gathered in Liverpool to hear about scientific developments from world experts in a wide range of cancer topics. NCRI is the biggest annual gathering of people who work in cancer in the UK.

Understudied and hard to treat

Dr Rudin kicked off the conference to bring us up-to-date about his work in small cell lung cancer. This form of lung cancer accounts for approximately 15 per cent of all lung cancers. Unfortunately, it’s an aggressive cancer with a poor outlook for patients. Patients don’t normally survive longer than nine or ten months and the disease kills over 220,000 people around the globe every year, making it a leading cause of cancer deaths.

The disease is initially responsive to standard chemotherapy drugs (cisplatin and etoposide) but it almost always comes back and does so quickly, as the cancer becomes resistant to treatment. It is an understudied cancer with a track record of failure in clinical trials. No significant treatment advance has been made since the 1970’s. But is there light at the end of the tunnel?

Hope for small cell lung cancer patients

Dr Rudin’s team have been studying why small cell lung cancer becomes resistant to chemotherapy so quickly. Using patient samples and mouse models they have identified a gene called Schlaffen-11 which is consistently switched off in chemotherapy resistant cells. So could switching this gene back on help? The team is now focussing on a group of drugs, EZH2 drugs, which might give us the answer.

This could be the light at the end of the tunnel: a new treatment for this aggressive cancer. The question now is, could these studies of acquired resistance apply to other types of cancer?

Worldwide Cancer Research are currently funding a number of lung cancer projects including developing new approaches to treating the disease and drug resistance. Here’s a handy map which shows you those projects.

Important lessons from yeast – more than baking and brewing

The final lecture of the first session was from Professor Iain Hagan, from the Cancer Research UK Manchester Institute, who has spent over three decades using yeast to study how cells reproduce, using processes called cell division and the cell cycle.

Yeast are made up of just one single cell and so are one of the simplest eukaryotic organisms. Eukaryotic means that the cells have a nucleus that contains DNA packaged into chromosomes, just like our own cells. Under a microscope “you can watch yeast cells actively dividing, producing two small cells, which get bigger and bigger until they then divide. It is very simple to spot changes in the cell division pattern” Professor Hagan explained. Some of these changes and faults in the cell cycle are also found in human cancer cells.

Professor Hagan then focussed in on the research by Sir Leland HartwellSir Paul NurseSir Tim Hunt and Professor Emeritus Yoshio Masui, and others, including previous Worldwide Cancer Research scientists, Professor John DiffleyProfessor Jon Pines and Professor Tony Carr which defined the master control mechanism in yeast known as the ‘cyclin dependent kinase complex’ which regulates the cell cycle. He also discussed how this has been translated to humans and ultimately resulted in the development of exciting new cancer treatments.  Although tiny yeast may physically look a far cry from humans, they actually have a number of similar genes and control mechanisms to us.

Finally, Professor Hagan argued that there “is still more to learn from yeast” through understanding phosphatase biology (his own area of work), spatial control and environmental control.

Not bad for a single cell organism!

Should we re-purpose drugs or make new ones?

The main talks of the conference were now over. But I wasn’t finished, as I headed to the debate ‘New tricks for old drugs?’- should research into ‘repurposing’ existing treatments and optimising their use be prioritised above research into developing novel agents? A really interesting question for myself as the Head of Research for cancer research funding charity.

There was a heated debate with good arguments presented by both sides. On the pro-repurposing side they talked about the increasing high cost of developing new drugs and gave examples of drugs successfully repurposed including thalidomide, originally developed to help morning sickness and found to have catastrophic side effects on developing foetuses, but now used as a treatment for melanoma skin cancer. A big advantage of repurposing is that the drugs have already passed stringent health and safety tests, speeding up the time it takes for them to be approved for patient use.

However, the opposition argued that these were all once ‘new drugs’ and to stop research into developing new drugs would be doing a disservice to future cancer patients. There is still so much we have to learn and so many cancer genes that have yet to be targeted by drugs. Cancer is also constantly evolving and changing, finding ways to evade our immune system and developing drug resistance – we must therefore continue to discover new ways to outsmart cancer.

The overall agreement was that there is a need for both. If drugs can be re-purposed this should be done. But to stop developing new therapies would be foolish.

Our charity have been involved in the repurposing of drugs. For example, we funded work which looked at the diabetes drug metformin, which was found to lower the risk of cancer. We also funded work which investigate a drug used to treat river blindness, which was found to have potential to treat breast cancer.

With my head swimming with all that I had heard today, the NCRI conference truly reaffirmed my belief that research is the best way to ensure no life is cut short by cancer. Then it was off to bed in my converted tobacco warehouse. If only those Victorians knew the damage tobacco would cause!

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