Tumor modeling

Kirill Stasevich, "Science and Life" 

One of the most unpleasant features of cancer cells is that as they are treated, they become insensitive to medications. It is obvious that they are helped by mutations that allow them to survive in adverse conditions. Moreover, it has long been noticed that, despite the genetic similarity of tumor cells, over time they acquire a large mutational diversity. And even if there are few new mutations, they will save cancer from therapy: substances that will kill most of the cells with the most common errors in DNA will skip cells with new, "non-standard" mutations, and such cells, of course, will go into growth. 

Attempts have been repeatedly made to create a model that would describe the growth and evolution of a tumor – with the help of such a model, it would be possible to predict both the actual increase in malignant neoplasm and the likelihood of drug resistance. And here the work of researchers from the University of Edinburgh and Harvard University looks particularly promising (see the press release of 3D models give a new perspective on cancer). The peculiarity of their approach is that they took into account both the genetic portrait of cancer and its three-dimensional structure. In other words, they compared mutational modifications with the internal structure of the tumor, with cell mobility. 

Usually, mobility is remembered in connection with metastases. However, thanks to the cells crawling from place to place, the original, primary tumor can also "improve". Let's say that a mutation has arisen in some cancer cell that can protect it from the drug. In order for the mutation to remain in the tumor, it is necessary that more cells with such a DNA anomaly appear. But for successful division, certain conditions are needed, from free space around to energy resources. And thanks to local mobility, malignant cells inside the tumor choose a convenient place for this. In addition, during division, with the doubling of cellular DNA, the probability that new mutations will arise increases. It is clear why the analysis of the three-dimensional structure of the tumor makes it possible to understand where to expect an increase in genetic diversity and the possible appearance of drug-resistant foci. 

A mathematical model that connects the genetics of cancer with its spatial structure was described by Martin Nowak and his colleagues in Nature: A spatial model predicts that dispersal and cell turnover limit intratumour heterogeneity. (We emphasize that in this case we are talking about dense, solid neoplasms, and, for example, the created model is unlikely to be useful for assessing the dynamics of blood cancer.) According to its authors, it allows us to understand how even one cell with a slight advantage over the rest can, thanks to its own mobility, thanks to the ability to find favorable conditions, can replace the previous tumor cells. Therefore, on the one hand, everywhere you can find the main mutations that are to blame for continuous division (without them, the tumor will not grow, and thanks to cellular migrations, such mutations will spread throughout the "body" of cancer), and on the other hand, the search for places where it is convenient to divide creates pockets of accumulation of additional DNA breakdowns, which can save a malignant neoplasm from anti-cancer therapy. It can be said that local mobility is an important condition for the evolution of a tumor. 

Such a model, of course, is not a drug in itself, but it indicates an important potential target for drugs: if we learn to suppress the ability of ordinary, non-metastatic cells to local wandering, we can limit the ability of the tumor to acquire resistance to therapy. 

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31.08.2015