Wednesday, 26 April 2017

Myc, Models and Tumour Growth

When I wrote the NEATG model of tumour growth, published in the journal PeerJ (, I focused on the behaviour of individual cells and on the role of cell competition and cell death in tumour growth. All models have to simplify and abstract, and the NEATG model does exactly that. The model steered clear of the molecular basis for the behaviour of the cells – my working assumption was that cells produce soluble factors and signalling proteins that mediate their cell-cell and cell-tissue interactions. It was one of the reasons I called the model NEATG (Non-physiological Evolutionary Algorithm for Tumour Growth – though as Sebastien Benzekry pointed out to me, the fact that the model has cells and tissues already makes it fairly physiological… ).

Despite the level of abstraction, the model clearly does show cellular behaviours that mimic aspects of tumour growth and response to cytotoxic chemotherapy.  A surprise for me was that the model showed that accelerated tumour regrowth following chemotherapy is driven by cell competition and the levels of cell death. I spent time looking at the research literature on these topics and found that my results were actually in line with clinically relevant phenomena – which is what makes the model interesting.

A recent paper from a group of researchers from the University of Bologna entitled MYC, CellCompetition, and Cell Death in Cancer: The Inseparable Triad  (available open access from the journal genes – it’s well worth a read), casts some interesting light on the topic. C-Myc is one of the most important of the master genes involved in cell cycle progression and tissue growth. It’s a transcription factor, which means it regulates the activity of other genes, and is often switched on permanently in tumours rather than coming on and off as required. It’s widely associated with a whole range of different cancers.

In this paper the authors review recent evidence from Drosophilia (fruit fly) models of cancer and how they are implicated in cell growth, cell death and cell competition. They outline the way that competition selects for cells that are ‘fittest’ and that less fit cells are effectively killed off – in just the way that they do in software in my model. The evidence that they outline suggests that one of the drivers for the behaviour of these cells is c-Myc, making it an important component at the physiological level missing from NEATG.The authors themselves make note of the results from the NEATG model:

Our findings suggest that CC [cell competition] is an innate process governing both cancer initiation and progression, where cell death fuels the clonal expansion of the fittest cells in the context. CC and apoptosis thus appear to be strictly linked one another, and emerge as fundamental cancer drivers also in a computational model of tumour growth, where several parameters of malignancy such as intra-tumour heterogeneity and accelerated repopulation have been taken into account.

For the next stage of work on this model I will be investigating the metabolic impact of cell growth in tumour growth, and the impact that cell death has on this. My prediction is that the model will show that populations of ‘super-feeders’ will emerge during tumour growth – and that chemotherapy helps to select for these populations of cells. However, as this stage I don’t really know that that’s what happens – I have to wait and see what the data tells me…

In the meantime I’ll finish with some final words from the team at Bologna :

Cells cooperate to build an organ and, in a similar way, they cooperate to build a cancer. Although the contexts are impressively distant, MYC-mediated cell competition seems to be at work in both cases with the same basic, sequential elements: cell–cell disparity in MYC contents, death of the cells with lower MYC levels, and proliferation of the cells with higher MYC levels. This stereotypical module shapes organ development and, possibly, cancer evolution. In growing tumours, an excess of dying cells is known to contribute to mass expansion, but the implication of MYC-mediated cell competition in this cancer trait has just begun to be investigated. Further research is warranted on the intricate “life and death” signals exchanged by confronting cell populations within the cancer community.

Wednesday, 22 February 2017

The Star Throwers Guide To Cancer

One of the reasons for starting this website was the wish to share information with patients, carers and other people directly affected by a cancer diagnosis. The site came out of a series of discussions I had with my son George while he was in the middle of his battle against osteosarcoma. We wanted a site that could be used to share science-based information that was likely to be useful, particularly for people looking for treatment options, as we often were. However,  I have to admit that in recent months the site hasn’t been getting the attention it used to – the number of new postings has been really light on the ground. One of the reasons for this has been that for a long time I had been working with the UK charity Star Throwers to produce a book that would provide a lot of that type of information in ebook and paperback form.

The Star Thowers Guide To Cancer, as the book is called, is now available via Amazon or, if you’re in Wymondham, Norfolk, direct from Star Throwers. The book covers similar ground to this website: science-based, heavy on information, concise and geared very much to looking at new treatment options. Does the world really need another new book on cancer? Book shops are full of new cancer books: memoirs, diet guides, histories of oncology and much more. But this one is different.

I like to think of this book as a ‘how to be a difficult patient’ guide. It shows you how to read the cancer literature. How to assess the breathless stories about new ‘cures’ that are frequently highlighted in the mass media. There is a detailed discussion of the tricky subject of cancer and diet. Searching for clinical trials and looking for treatments abroad are also covered in some detail. Local ablative treatments such as cryoablation are covered, including the vital information on where to look for these useful but underused treatments. Finally, there is also a chapter on drug repurposing, a topic I have covered here many times and which I now work on pretty much full-time.

In the past I have considered taking the best articles from this site and putting them together as a single download via PDF. But there’s no need now. This book provides the best of this site and much, much more.