cancer and the cell cycle

Last Friday I came to the Max Planck Instute for Cell Biology, at the other side of Dresden, to attend a series of seminars including one from a colleague and friend of mine, Babis Hatzikirou, about the cell cycle.

The classical view on the cell cycle can be seen in this picture that I took from Babis's presentation (and which I suspect he took from somewhere else :)):
This is quite interesting although not precisely research news. Most of the cell cycle is of course devoted to interphase and only a minority of the time (assuming that the cell is not in arrest mode) is devoted to create a copy of itself (through mitosis and cytokinesis). The cell cycle is controlled by a finely tuned balance of proteins cdc2-cdc13 and a number of checkpoints make sure that before changing the phase of the cell cycle everything is in order. These checkpoints and their associated proteins (such as the famous TP53) are quite critical to prevent tumour formation as they impede the growth of cells that need DNA repair.

The cost of validation

Many interesting speakers in this workshop in Dundee but most of them fall in the mathematics part of biomathematics. Among the few who do not is the biologist Vito Quaranta (Vanderbilt University). Although I have been told many times that things are changing for the better in that respect, the scarcity of life scientists and medical doctors in these type of conferences tells me that there is still a lot of work to do to convince them that computational and mathematical biology is not only relevant but necessary.

The talk from Vito Quaranta was not so much about science as about doing science at the interface between theory and experiments. He is lucky to count with the resources of the Vanderbilt Integrative Cancer Biology Center. Otherwise the problem of validating the mathematical and computational models with theoreticians come with would be next to impossible. This theoretical models make a number of assumptions about the properties of tumour cells, tissues and micro environments and predict outcomes that in many cases have to be contrasted with in vivo and in vitro experimental results. This experimental work is really challenging given the level of fragmentation of knowledge and expertise in biology and medicine. Different labs with different experimental techniques, machinery, cell lines and the necessary permissions to perform animal experiments and access human clinical data are required to validate one single theoretical model. That means that unless centres like the one in Vanderbilt become much more common most theoretical models will remain experimentally untested unless they proof to come out as the result of the consensus of the theoretical biology community.

Telomeres, cancer and aging

One quite fascinating thing in animal biology is the question of immortality or, to be more precise, the lack of it. While most unicellular organisms can divide for as long as they have the luck to find resources and space to do so, human cells can divide only a limited amount of times (approximately around 50 times, although this does not apply to stem cells that can divide an unlimited amount of times). In principle the limitation in divisions for most human cells is due to a mechanism that has been evolved and is not an intrinsic limitation. The cancer hypothesis is that the limitation makes the appearance of cancer more unlikely. If a cell is limited to just a few divisions, if it acquires a mutation that mutation is unlikely to spread to far.

The reason for this limitation are the telomeres, situated at the end of the chromosomes, that get shorter each time the cell divides. Once these telomores reach a critical size and become to small the cell will enter a state called senescence by which they will not divide again.

This is an interesting link in which they talk about this and how in the next few decades we might know enough about the effects of limited cell replication in human life expectancy, how to increase it (maybe for ever) and how to do that avoiding nasty side effects (like increased probability of dying from cancer). The website in which this is hosted is covering all sorts of news, many of them of dubious scientific interest, but the information in the link looks sound.

On the other hand in a more reliable source (PNAS) there is a nice study on how telomere dysfunction can cause genetic instability. They work on a disease known as Werner syndrome but it is quite useful stuff for cancer research. This Werner syndrome results in people aging prematurely and researchers at the Salk institute have found how extra short telomeres can be the source of the problem.

Online introduction to computational oncology

I have recently found an interesting introduction to computational oncology on the website of Paul Macklin, a graduate student at UC Irvine.

The website comes complete with the stages of cancer evolution (not the usual 6 capabilities of Hanahan & Weinberg but a version a little bit coarse grained for my taste) and therapies. He also points out some of the challenges that need to be addressed such as explicitly incorporating the tumour microenvironment (it is a well known fact that some tumour cells behave like regular healthy cells if left in a different microenvironment from the one it comes from). Useful for people who might want to understand some of the aim of the papers I mention in my reviews.