http://commons.wikimedia.org/wiki/File:Chest_x-ray_(cancer).jpg Credit: Wikimedia Commons
“I lost both parents to lung cancer. The doctors did what they could, but treatments back then were not what they are today. Lung cancer is a formidable opponent. Young researchers should take this opportunity to learn from the best – families like us are willing them to succeed.”
These were the words of one of Manchester’s most famous adopted sons, the legendary Sir Alex Ferguson, who opened the inaugural Cancer Research UK Lung Cancer Centre of excellence conference in the city with a rallying call via video for why lung cancer research means so much to him.
Lung cancer is the world’s biggest cancer killer: it’s the second most common cancer and claims more than 35,000 lives a year. And while rates are slowly falling in men, they’re still rising in women – a worrying trend that reflects smoking patterns over the last few decades.
Despite the progress we’ve seen in many types of cancer, lung cancer survival is still poor. And we’ve made it one of our top priorities to change this.
Back in 2014, we announced the new Lung Cancer Centre of Excellence – a big step towards accelerating progress against lung cancer.
And the end of December saw the Centre’s first ambitious conference take place, bringing together the world’s leading lung cancer experts to share their latest findings. And getting everyone in one room gave researchers the opportunity to fire up new research ideas and speed up progress in understanding and treating the disease.
The event included talks from biologists, geneticists, immunologists, physics experts and clinicians. Here’s a summary of the top themes that came out of the meeting.
Lung cancer experts are unanimous on one point; survival is low because many patients are diagnosed too late to be given life-saving surgery.
One possible solution to this problem is screening – testing healthy people with no symptoms for signs of lung cancer.
Dr Sam Janes, a specialist consultant at the UCL Cancer Research UK Lung Cancer Centre of Excellence, went through some of the advantages and disadvantages of giving people at high risk of lung cancer (for example heavy, long-term smokers) a type of scan, called a low-dose CT scan, to spot tumours earlier.
It’s a complicated subject – on the one hand, a scan can potentially detect lung cancer at an early stage, meaning a patient’s chance of having successful treatment is higher.
But on the other, screening smokers might offer them false reassurance and de-motivate them from attempting to quit – this is something that would need to be looked into.
The scans themselves also give out radiation – albeit small doses – that can increase the risk of developing other types of cancer. And an abnormality spotted on a scan doesn’t definitely mean the person has lung cancer, or that it will grow aggressively and put life at risk. So there are concerns that some people might have unnecessary and risky operations or be treated for cancer that would not have harmed them.
It’s a complex topic, and it’s not clear yet how the benefits and harms stack up against each other.
Professor Avrum Spira, from Boston University in the US, is tackling some of these problems from an exciting and innovative angle. He believes we need tests that could be used alongside scans to help make decisions on whether a person needs an invasive diagnostic procedure. And his team has developed a test in the US to try and do this.
When smokers underwent surgery to diagnose a suspicious growth in the lung following a CT scan, he collected a sample of cells from the airways at the same time.
He tested the cells to find out the general level and pattern of genetic mistakes caused by smoking, and found the results from the airway cells gave a good indication of how likely the growth was to be cancer. His hope is that one day cells taken from the airway – or even the nose – could be used to decide whether someone needs an invasive biopsy or can be monitored with scans, reducing the number of people who are given unnecessary treatment.
“The nose knows,” he told the audience. We’ll wait and see if he’s right.
Tackling lung cancer over time
Over the last couple of decades we’ve seen the era of precision medicine dawn – treatments that specifically home in on the genetic faults underpinning different types of cancer.
But while many lung cancers respond well to targeted treatments, there’s a huge problem: resistance. In these cases, the cancer returns and treatment stops working.
But in recent years researchers have shown that most tumours are a mix of genetically different groups of cancer cells that can change and evolve over time, helping this resistance take hold.
Understanding the genetic differences between lung cancer cells and the changes that happen during treatment is going to be critical in re-sensitising them, or knowing what other treatments to give the patient. But how do we best analyse and monitor cancer over time? Taking repeated samples via surgery is usually not an option, taking too much of a toll on patients.
Professor Caroline Dive, joint lead of the Lung Cancer Centre of Excellence based in Manchester, is hoping that blood samples may be the answer. She’s focusing on what cells that have broken away from the tumour and entered the bloodstream can tell doctors about the disease – how likely it is to come back, and how effective new treatments are.
Her team has been able to isolate these circulating tumour cells from patients and recreate lung cancer tumours in mice. And in developing this approach they have found a promising new drug combination.
Other exciting approaches to monitoring lung cancer may come from looking at DNA shed by tumours into the blood, and using detailed imaging to predict cancer’s behaviour by analysing its size, shape and location.
As well as tracking the changes in lung cancer over time, another key focus of the conference was on better treatments.
Preventing resistance is more effective than treating resistance
– Dr Pasi Janne, Dana Farber Cancer Institute in the US
Most lung cancers respond well to the different treatments available – chemotherapy, radiotherapy, and certain ‘targeted’ treatments. But they often come back resistant to these therapies.
One of the hot debates at the conference was how best to tackle this challenge. “Preventing resistance is more effective than treating resistance,” said Dr Pasi Janne, from the Dana Farber Cancer Institute in the US.
Some doctors were in favour of combining more therapies for a patient’s initial treatment, with a view to stopping any cancer cells surviving and becoming resistant.
Others favoured a less intensive front-line approach, and preferred developing strategies to keep patients’ lung cancer under control long term – turning it into a chronic disease rather than one that kills. This approach would need a better understanding of cancer evolution and new treatments to stop resistant cells growing.
Both lines of attack have advantages and disadvantages, but one thing is for certain – we urgently need more clinical trials to help doctors find out the answers.
No conference would be complete without mention of the most exciting type of treatment to emerge over the last few years – immunotherapy.
The session was introduced by Professor Tim Illidge, who joked that the rising success of immunotherapy bore a striking resemblance to the inverse drop in form Manchester United had seen in recent years.
A big challenge for immunotherapy is working out who might benefit from it. And there was a lot of interest in which tumour cell molecules make good targets for the immune system, and whether these molecular ‘red flags’ were present on all of the cancer cells or just groups of them.
The bottom line, from leading experts like Dr Sergio Quezada from UCL in London, was that the ‘quality’ of the red flag was going to be critical in boosting a strong immune response against cancer.
And there are lots of promising treatments in the pipeline – drugs that stop cancer cells hiding, treatments that re-educate immune cells, and even vaccines that turn immune cells against cancer.
There’s a lot we still don’t understand about immunotherapies and who is going to benefit from them, but there’s clearly huge determination from researchers to find this out. Clinical trials testing immunotherapies for lung cancer patients are underway, with many questions over timing and the best way to combine them with other treatments still remaining.
Talk leads to action
While there’s still a long way to go, we are making progress for lung cancer patients. And there was a great sense of optimism from the scientists and doctors gathered in Manchester.
Just because things haven’t worked in the past, doesn’t mean they won’t in the future if we keep improving things
– Professor Julian Downward, Cancer Research UK
Bringing these experts together initiated lots of exciting conversations – boosting each other’s knowledge and possible new avenues opening up where scientists could work together across the UK, Europe and beyond.
For too long lung cancer hasn’t had the attention it needs. That is now changing.
“I first started working on this when my eldest daughter was first born,” said Professor Julian Downward, from the Francis Crick Institute, as he explained an approach to targeting a weakness in lung cancer cells. “We’ve now just celebrated her 13th birthday.”
“Just because things haven’t worked in the past, doesn’t mean they won’t in the future if we keep improving things,” he said.
And based on this conference, there’s a real sense that is happening.