One of the most cutting-edge areas of cancer research is the study of the cancer microenvironment.
The microenvironment is the habitat in which a tumour lives: the support cells, protein scaffolding, signalling molecules and blood vessels that surround cancer cells in a tumour. It’s only relatively recently – in the past few years – that researchers have begun to appreciate the enormous impact it has in cancer.
At a recent ICR talk I attended Dr Paul Huang, one of the team leaders in our Division of Cancer Biology – and
some of whose work is focused on studying the microenvironment – referred to cancer as a dystopian society. The analogy is a good way to understand the disease: cancer cells, much studied and the targets of almost all current cancer treatments, are its leaders, but we cannot comprehend cancer without understanding the society as a whole.
It’s a surprising fact that cancer cells are able to enslave other types of cell to their cause. For example, cancer-associated fibroblasts are not cancerous themselves, but play an important supportive role to cancer cells by shaping the tissue surrounding a tumour to better suit their needs.
Normally fibroblasts are the engine rooms of many types of tissue: large cells that churn out the protein fibres that help to hold everything together, forming the supporting framework within which cells live, communicate and move.
But in cancer, fibroblasts remodel the matrix of protein surrounding tumours, promoting new blood vessel growth – important in feeding a growing cancer – and helping to enable the eventual invasion of cancer cells into new sites. Without cancer-associated fibroblasts, some tumours could be held in their original location and prevented from spreading to new sites in the body.
Work from another team at the ICR, led by Dr Fernando Calvho, has showed that
activation of a gene called YAP is a signature feature of mouse breast cancer-associated fibroblasts. The gene is likely to play a similar role in human cancer, too.
Although this sort of discovery underlines the amazing complexity of cancer – as well as the fact we still have huge gaps in our understanding of the disease – it offers hope by giving a tantalising glimpse of a future in which there are more treatments that target cancer’s microenvironment, and not just cancer cells themselves.
Evolution – and new treatments?
It’s timely to think about the microenvironment this week, when we’ve officially launched our new Centre for Cancer Evolution (here’s
a link to an in-depth feature about the Centre on BBC Radio 4’s Today programme). One of the aims of the Centre is to understand how evolutionary pressures shape cancer biology.
As with the evolution of organisms within any ecosystem – from
finches in the Galapagos Islands, to
guppies in the Caribbean – the ultimate drivers of change in a population are genetic and environmental variation. Cancer is the same: every cancer is its own dynamic ecosystem, but with cells, blood vessels and proteins standing in for animals, rivers and soil. The cancer microenvironment has a fundamental influence on which cancer cells will survive, and which will die.
Researchers have been studying the microenvironment for many years, and some existing drugs do target it – for instance, bevacizumab targets angiogenesis, the growth of new blood vessels.
But it’s a truly forward-thinking idea – which our scientists at the new Centre will explore – that changing the microenvironment around a tumour could promote the survival of less harmful cancer cells, giving them an edge in the evolutionary battle against their more dangerous neighbours.
Traditional approaches to developing new treatments have been overwhelmingly successful in some cancers, with survival prospects and cure rates transformed over recent decades. But the problem of drug resistance – when cancer cells evolve to avoid the problems caused by a treatment – means that for some cancers, and particularly the most genetically diverse ones, new approaches are needed to help find effective treatments.
New treatments that control elements of the cancer microenvironment could help tip the balance away from the most dangerous, metastatic cancer cells in favour of those which are less likely to spread and cause harm throughout the human body.
Image credit
K. Hodivala-Dilke & M. Stone, Wellcome Images: Creative Commons by-nc-nd 2.0 UK: England & Wales. The image is a colour-enhanced, freeze-fracture scanning electron micrograph of a blood vessel that has grown into a melanoma and is providing nourishment to it.
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