Image: A high magnification image of ovarian clear cell carcinoma. Credit: Michael Bonert Licence: CC BY-SA 3.0
Here at the ICR, we are making great inroads in finding new treatments and improving the lives of people who have cancer. To make sure that we treat cancer cells but not healthy ones, we need to know what makes cancer cells tick, and what makes them different from normal cells.
Research into the biology of cancer cells is fundamental to our understanding of how to tackle the disease.
I met with Professor Jon Pines, who heads up our Cancer Biology Division to discuss the past, present and future of research to better understand cancer.
Mistakes during replication
Back in the 1950s and 60s, researchers here at the ICR provided the first conclusive evidence that the basic cause of cancer is damage to DNA. Six decades on, DNA damage still forms an important focus of our basic biology research.
When a cell divides, its entire DNA needs to be copied to go into the new cell. This is a hugely complex task, and there’s a lot that can go wrong in the process. Healthy cells have rigorous control mechanisms in place to ensure that any copy mistakes are repaired, but in many cancer cells, this DNA repair mechanism is broken.
“Cancer cells often have inactivated some of the DNA damage repair mechanisms, and so they’re quite vulnerable in that area,” Professor Pines explains. “On top of that, cancer cells often make mistakes during replication, introducing more DNA damage than you would find in normal cells.”
Professor Wojciech Niedzwiedz is one of the researchers in the Division looking into DNA repair in cancer. His team studies the way cells can detect and repair DNA damage, particularly when DNA breaks occur in both strands of the genome.
DNA is packaged up by wrapping it around proteins called histones to form a structure called chromatin, and this also affects how DNA faults can be repaired. This is the focus of Professor Jessica Downs’ work, who studies the influence that chromatin and, histones have on DNA repair and the proteins that govern it.
Dr Gideon Coster, who joined the ICR at the start of this month, will be looking to uncover how difficult-to-replicate sections of the DNA are copied in cancer cells compared with healthy cells.
Once DNA is duplicated in the preparation for cell division, it needs to be evenly distributed – that’s where Professor Pines’ own research comes in.
“We try to understand how, when a cell divides, the two daughter cells receive an identical set of the packages into which DNA is wrapped up, called chromosomes.”
In 2016, Professor Pines’ team made a major discovery when they found how this process contains a ‘safety catch’ that prevents cells from dividing until DNA is distributed equally between the two daughter cells.
The Division of Cancer Biology studies the complex interplay of genes, proteins and biological processes that drive the development, growth and spread of cancers.
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Large-scale protein analysis
Since the human genome was fully sequenced in 2003, large gene sequencing projects have led to important insights into the genetic processes that drive cancer. Now, new technological developments have made similar large-scale analysis of proteins in cancer a reality.
“The levels and interactions between different proteins are really the next important thing to understand about what goes wrong in cancer,” Professor Pines tells me.
Soon to join the ICR is Dr Norman Davey, a bioinformatics expert interested in interactions between different proteins. His work will focus on identifying new surfaces of proteins that are involved in binding to each other.
“Analysing proteins on a large scale is particularly important because, as well as DNA faults that change the proteins themselves, cancer cells have big changes in the ratios of proteins that are expressed,” says Professor Pines.
That’s exactly what Dr Jyoti Choudhary, an expert in protein analysis, is looking into. She uses a technique called mass spectroscopy to identify the sets of proteins in a cell and see how they change in cancer. Dr Choudhary also manages the ICR’s proteomics facility – performing protein analysis for researchers across the whole of the ICR.
Disrupted signals within cells
Another important area of basic biology research here at the ICR looks at the way signals within cells are disrupted in cancer. These molecular signals are key to understanding how cancer cells grow, divide and spread.
Dr George Poulogiannis’ research focuses on how cell metabolism changes in cancer – looking at how signalling pathways are rewired to affect the way cells use energy and nutrients to fuel their growth. Earlier this year, he helped discover that an amino acid called asparagine is essential for breast cancer spread.
The signalling pathway that holds Dr Sebastian Guettler’s interest is affected in many cancer types, and is closely linked with the protection and maintenance of telomeres, the ends of chromosomes. Dr Guettler studies a protein with an important role in both processes, tying in with structural biology.
Dr Chris Bakal studies how cell signalling changes the shape of cancer cells, and the way they move and spread. Through studying the differences between cancer cells and healthy cells, Dr Bakal aims to better understand how cancer cells are able to migrate through the body to where they shouldn’t be – a process called metastasis.
Advances in technology have made a huge difference to our basic biology research, says Professor Pines.
“The sensitivity and resolution of microscopes has been getting better and better. This means that we are now able to study processes in the cell that we were unable to see before – either because they happened too fast, or because the proteins involved are at too low a level.”
“In addition, we are strengthening our expertise in proteomics and bioinformatics. Those enabling technologies allow for an important synergy between basic biology and other areas of cancer research, such as drug discovery, and will form an important part of the future of the ICR.”
In the future, Professor Pines sees an important role for basic biology in the context of the ICR’s growing interest in cancer immunotherapies.
“It looks as if cancer cells making errors in division is one way through which the immune system can be primed to recognise cancer cells,” he explains.
“DNA damage, errors in DNA replication, or problems in cell division itself look as if they can be used in order to stimulate the body’s immune system to recognise cancer. This is of course of great interest in terms of new types of therapies, and being able to attack types of cancer that have been difficult to treat before.”
As our understanding of what drives cancer changes, so does our approach to tackling it. Much of our basic biology research is already informing other research here at the ICR – and there’s no telling where our next discovery about the fundamental processes in the cell might lead.
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