Blood tests, microbes, immunotherapy and more

University of Cambridge| Thu Apr 13 11:04:37 EDT 2017
Blood tests, microbes, immunotherapy and more

Last week, some 26,000 scientists and doctors gathered in Washington, D.C. to talk about one thing: cancer.

Each year, the American Association for Cancer Research (AACR) brings together some of the brightest minds from across the globe to share progress in their field of research. From unpicking the molecular ‘nuts and bolts’ of cancer cells to testing out potential new treatments, the breadth of science covered was vast, mirroring the scale of the problem at hand.

And though the 5-day programme was jam-packed with presentations, it was soon apparent there were some areas generating the most buzz.

In this blog post we’ll round up a selection of some of the most exciting research presented to give a flavour of some of today’s hottest topics in cancer research.

For many cancer patients, a sample of their blood contains much more than just blood cells.

As a cancer develops and progresses, it can shed identifiable marks into the blood in various different forms, including tumour cells, strands of tumour DNA and its chemical cousin RNA, and tiny DNA-containing sacs called extracellular vesicles. Scientists can then scan these like barcodes to learn more about more about the tumour’s underlying biology and genetics.

These blood tests are called liquid biopsies, and it was clear from the work presented that scientists are now exploiting this easy access resource in a number of different ways.

Dr Max Diehn, from Stanford University in the US, showed that tumour DNA in the blood could reveal that a person’s lung cancer has returned some 6 months before evidence shows up on scans, offering a potential window of opportunity for treatment. And work by Dr Victor Velculescu, from Johns Hopkins University in the US, suggested that it’s possible to use this DNA to track whether immunotherapy drugs are working, which again could have important implications for treatment.

While it seems the field is developing rapidly, there are still hurdles to overcome before liquid biopsies can become common in the clinic. For example, the cancer cells and tumour DNA found in blood are only present in miniscule amounts. It can be difficult to pick up these low levels, so scientists need to develop ways to ramp up the sensitivity of detection.

But, as Professor Carlos Caldas from our Cambridge Institute pointed out, just like turning up the volume on a fuzzy radio station, this could generate too much background ‘noise’ that could drown out the signal that scientists want to pick up and make it more difficult to analyse.

Alternatively, suggested Dr Nitzan Rosenfeld, also from our Cambridge Institute, the key to getting more information from liquid biopsies could be to widen the net and search multiple tumour markers in the blood, rather than focussing on one or another.

“How do you find a needle in a haystack?” asked Rosenfeld.

“Look for multiple needles.”

Our bodies are loaded with bacteria, but they’re more than just microscopic freeloaders. They help our bodies out with a range of functions, such as breaking down food and making hormones. But it also seems they have a role to play in cancer treatment, influencing its likelihood of success in some cases.

One interesting talk on the matter was given by Professor Laurence Zitvogel from Institut Gustave Roussy in France. Her findings suggest that gut microbes could be used to distinguish those who responded to certain immunotherapy drugs from those who didn’t.

Looking at lung and kidney cancer patients, she found that people whose white blood cells reacted against two particular types of gut bacteria tended to have better survival after immunotherapy treatment. She also found that patients who were given antibiotics shortly before or after immunotherapy tended to have worse survival.

This work sparked debate at the conference because for some patients, these antibiotics could be helping to combat life-threatening infections. But the findings also raise the possibility that manipulating peoples’ gut bacteria could offer a simple way to potentially boost the effectiveness of treatment.

It will take further research to test this idea. But the potential was backed up by Professor Eran Segal, from the Weizmann Institute in Israel, who is exploring the potential of personalised cancer treatment and nutrition guided by an individual’s microbial inhabitants.

Once a drug has been developed, there’s often a fair amount of tinkering required to work out how to get the best results from it.

One approach that appeared to be common among presenters was a case of marrying up different treatments to give combinations that are more powerful than the individual drugs used solo. For example in the field of immunotherapy, one of our scientists, Dr James Larkin from The Royal Marsden Hospital in London, showed that advanced melanoma patients in his phase 3 clinical trial did better on a combination of two immunotherapy drugs (ipilimumab (Yervoy) and nivolumab (Opdivo)) than when the drugs were used alone. But these combined treatments come with the added challenge of worse side effects.

Various presenters showed that immunotherapy can also be combined with other existing drugs, and this approach is showing some early promise. Others are trialling combinations with innovations such as cancer-fighting viruses. For more on the immunotherapy trials presented at the conference, check out our news report.

Just as two drugs may be better than one, the adage “two heads are better than one” seems to be particularly pertinent for cancer research to progress. This was the message that former US Vice President Joe Biden was keen to express during an update on his ‘Cancer Moonshot’ initiative, among many others throughout the conference.

“For decades, we thought we could tackle cancer one discipline at a time,” said Biden during his emotive talk. “That’s not how cancer operates; it uses every tool at its disposal.

“That’s why we have to use every discipline cancer does, and we’re starting to do that in a more coordinated way, bringing new important players into the fight like data scientists and computer engineers.

“Collaboration increases the chance exponentially that we can find answers. We can do more together than we can by working alone.”

It can be difficult to go a week in science news without hearing about CRISPR, the exciting gene editing tool that’s often stealing headlines. And AACR was no exception. The number of projects featuring this innovative technique show that labs are using it more and more, and for good reason.

CRISPR is helping scientists unravel the genetic and molecular underpinnings of cancer, developing our understanding of how the disease develops and progresses. For example the Broad Institute’s Project Achilles is making significant strides in using CRISPR in cancer cells in a dish to unpick the genetics behind the hardiness of cancer cells. In the future, these discoveries could be used to develop new treatments that target the cancer’s weak spots.

While that may perhaps be one of the most common applications of CRISPR technology in cancer research, it’s certainly not the only one. An impressive demonstration of the tool’s scope was given during a series of talks on the final day, each highlighting different uses of the system.

Perhaps the most intriguing was that of Dr Louis Staudt, of the US National Cancer Institute, who has been using CRISPR to find out why some lymphoma patients respond exceptionally well to a targeted drug called ibrutinib, while others don’t.

They can now divide a particular type of lymphoma into distinct groups, which could help guide treatment.

The thousands of scientists who gathered at this event, and the breadth of science on show, highlight how many unique goals for there are in research.

While each of these has different tactics, they all have a common ground: beating cancer sooner.

And this colossal gathering serves as reassurance that we’re getting there, one step at a time.

Justine 

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