New Ideas in Cancer

It seems that the opening up of forests by roads for logging companies could be leading to the demise of forest elephants in West Africa, according to a study published by a team of scientists the World Conservation Society (WCS). They trekked over 8000km through the African forest to take a census of elephant numbers.

Counting forest elephants is not an easy business - partly as dense forest means that you can't just fly over the area to spot and count them unlike their savannah dwelling cousins, and also because you don't want to get too close to the elephants as they are well known to be aggressive. So instead the research team searched for clues that the elephants left behind in the forest - the most reliable being their dung.

Worryingly they found very low numbers, with less than one elephant in each sq km of forest. More concerning is that they found less dung close to the roads. These roads have been built penetrating further and further into the forests to allow timber companies access to the valuable trees. Instead of finding evidence for live elephants close to roads, they actually found more carcasses with their tusks removed. This suggests that these roads bring not just the logging companies but also elephant poachers that come for the ivory and the meat.

Trading ivory is banned by the Convention on International Trade in Endangered Species (CITES) but since 2004 prices have quadrupled - it is now worth over $850 /kg. Sadly this continuing demand for ivory could lead to these incredible creatures being wiped out.

Humpback whales are record breaking swimmers - they have been recording as migrating further than any other mammals, according to scientists in the USA. They clocked the whales as travelling over 5100 miles from Costa Rica in Central America to their feeding grounds in Antarctica.

They used a traditional method to collect the data, rather than complex satellite tracking - recognising individual whales by the shape and colour of their tails. As a whale ages, it get small nicks and cuts in its huge tail, as well as species like barnacles taking up residence on it. This means that individuals can be told apart by taking a photograph and studying the differences in the tails. The researchers collected photos of at whales in both Costa Rica and Antarctica and recognised the same whales in both areas.

Apart from the fact that the whales migrate so far, another interesting part of this study is that it proves that humpbacks do migrate to warmer waters in the winter. They also used satellite data on sea surface temperatures to show that in years where the temperatures in Costa Rica were cooler, the whales actually travelled even further north, away from Antarctica, to warmer areas to stay comfortable over the winter before swimming all the way back down in the spring to the feeding grounds.

The idea that skills we have acquired in life are inherited is known as Lamarckism, and although this was once a widely held belief it is now thought to be wrong. Skills and abilities are most likely to have developed as a result of the environment you were brought up in, a case for nurture rather than nature. There is some genetic data to suggest that certain abilities, like the ability to recognise 'perfect pitch', have a genetic component. This wouldn't mean you would be born with musical ability, but being able to reproduce music more accurately than most may make you more likely to decide to get into music, and develop your musical skills.

Sabina -   To begin my quest in exploring the role of stem cells in cancer, I thought I'd find out what a stem cell is; so I went to the Wellcome Centre for Stem Cell Research, and I asked a stem cell researcher.Jason Wray:  Stem cells are a really amazing cell type, they are defined by two very special properties; the first is self renewal, the capacity to make identical copies of themselves, and the second property which defines a stem cell is the ability to differentiate into more specialised cell types.  We break stem cells into two different categories:  Embryonic, which have the capacity to make any type of tissue, and more specialised stem cells which we call adult stem cells, which are restricted to a particular type of tissue, be it brain tissue, skin tissue and so on.Sabina -   I'm off to see John Stingl, breast cancer specialist in Cambridge University's Pathology department, to ask him what cancer is and how stem cells are involved.John Stingl:  We actually believe that cancer is a disease of stem cells.  Stem cells are normally involved in the formation of an organ, and all cancer is, is organ formation gone wrong.  Cancer is a disease where you require multiple genetic mutations to get a tumour.  For example, you don't just have one mutation and get a tumour, because if that were the case, we would all be dead. We actually find we need 5-7 mutations.  The probability of a cell getting a mutation is actually very low, like one in a million, like trying to win a lottery prize.  However, if you have a cell that has the capacity to produce lots of daughter cells, such as a stem cell, if you can mutate a stem cell, then that stem cell produces a million daughter cells, now you have a million cells which already have one genetic mutation.  The probability of one of those cells getting another mutation is actually quite high, and then the cell that has mutated will produce a million daughter cells and one of those will become mutated and so on.  That's how you can acquire five mutations.Sabina -   A lot of research is being conducted to look at how stem cells work and what their role in cancer is.  Brian Huntley is an expert in stem cell self renewal and he's working with leukaemia at the Cambridge Institute for Medical Research.  I asked him how current research is directed by a need for cancer treatment.Brian Huntley:  Treatment of malignant disease is still very ineffective and most patients have relapse and progressional disease, many still die from malignant disorders. However when you initially have a tumour, regardless of the tumour type and regardless of the therapy; whether that be chemotherapy, radiotherapy or some of the newer immunotherapies, there is usually a reduction in the size of the tumour mass.  Sometimes it's very dramatic and sometimes it actually disappears.  However we know that the vast majority of patients have re-growth of that tumour, either in the same place of what's known as a metastasis, growth in another place.  That would suggest, following on from the cancer stem cell hypothesis, that we are killing the cells that form the bulk of the tumour, but are not able to re-grow it, whilst we are sparing the cancer stem cells.  We would ideally want to target the critical cells which cause the propagation and the re-growth of the tumour.  We need to know more about these cancer stem cells and how they differ from normal stem cells, and we need to be specifically targeting them to show improvements in cancer therapy.

Andrew -   What we set out to do was to try to understand what role a specific set of genes that occur in the genomes of all individuals, called Kinases, have on the progression of the disease (cancer).  These cells are very interesting because they govern most of the molecular processes in the cell.  They act like molecular switches, turning things on and off.  Cancer cells are those that grow when they shouldn't, where they shouldn't and how they shouldn't and nearly all of these processes have a Kinase involved somewhere in the pathway that governs that process.  We were interested to know which of those genes to think about in terms of drug targets.  We knew also from the past 20 years of research that if you look at the genes known to be mutating, protein Kinases show up more frequently than any other gene family at the moment.Kat -   So they are the real bad guys?Andrew -   At the moment they appear to be the bad guys we understand the most about.  The linchpin for deciding to work on those genes, out of all the 20-odd thousand that exist in the human genome, was that it's the one gene family that we know how to make drugs against.  There are several startling examples of understanding the genetics of a tumour via a mutated protein Kinase and developing a small molecule that has a high level of efficacy in patients.  So we wanted to understand the genetics of cancer and also start a family where if we found something there would be shorter route to translation in terms of patient benefit.Kat -   You have looked at 500 genes in 200 types of cancer. How do you go about looking at that many genes for that much information?Andrew -   We used what will in a couple of years be called 'stone age' technology, the same technology we used to sequence the human genome; called Capillary Based Gene Sequencing.  Out of those 500 genes we looked at all the bits that encode them, amplified them using a polymerase chain reaction from all 200 samples across these 500 genes, which works out to be about 10,000 fragments per sample, and sequenced them from both ends.Kat -   That's a lot of work! How do you cope with that much information? Presumably you have incredible computers to process it all.Andrew -   Yes, we have an excellent group of 14 people in the cancer genome project who are bioinformatitians.  They are a brilliant group who organise the data and give it to us in terms we can understand.  They actually allow us to find a single experiment amongst the millions that have been done, which is very important. It's collaboration between lab scientists, computer scientists and the people who integrate the information between the two.Kat - So what were you expecting to find?Andrew -   Well, from the work that we had done earlier we found a frequently mutated Kinase called B-raf in the tumor type called melanoma.  This particular Kinase is mutated in about 60% to 70% of this lethal disease.  We were hoping to find the same sort of pattern when we look at Kinases across a broader set of cancers.  If 60% of a gene is mutated in a tumour it would make a good drug target, if you can make a molecule to turn that gene off.So we when we started looking at these 200 cancers we quickly began to understand that this particular example looks like the exception rather than the rule.  The rule looks like a more widely distributed set of mutations across a larger number of genes, so we found about 1000 mutations in 200 samples, and we believe about 100 of those are driving cancers in that group of 200.Kat -   So this is more than you expected?Andrew -   It's quite a bit more than I would have expected.  We hoped it would be lots of spikes rather than this rumble of noise, because it's more tractable to deal with spikes in terms of therapeutic development.Kat -   So do you think that means you've potentially more targets to have a go at?Andrew -   I think that's exactly right.  What it does is it opens up a window into understanding just how complex the disease is and that's a daunting prospective. I think what it also does is allow you to begin to integrate this information into understanding what processes, pathways and signalling circuitry is turned on or off in particular cancers, it may give you the opportunity to not only go after the gene itself but also the pathway.Cancer is a complex disease we can't get away from that so we're going to get in there, roll up our sleeves and get to grips with the ugly reality of it.Kat -   So you've looked at Kinases, this particular group of signalling molecules.  Are there any other molecules or family of molecules that are next on your hit list?Andrew -   We started a study running towards the end of the Kinase study looking at another group of about 4000 genes. We're also going to use a larger number of tumours, about 100 cancers per set.  This is comprised of essentially any gene family where there is already one member known to be mutated in cancer, promoting the idea that they may be clustered by family or by function.  For example we know that DNA repair is not working particularly well in a lot of cancers.  This would involve things like phosphatase, which turns things back off after Kinases turn them on, or other gene families that are involved in signalling pro-growth or pro-apoptosis cell growth division. These are all the usual suspects or at least as good as we can come up with on that list at the time.Kat - so that's going to keep you busy for a while!Andrew -   Yes, sadly, I don't think we'll be working our way out of a job anytime soon.

Non Melanoma cancers (skin cancer which does not affect the melanocytes, or skin pigment cells) are by far the most common cancers in the western world. It's largely because the skin is the barrier which is protecting you from the environment. Exposure to sunlight, if uncontrolled, could damage the DNA in your skin and give you cancer. Other types of damage that could result in cancer include exposure to harmful chemicals.Rates of Melanoma (skin cancer which does affect the melanocytes, or skin pigment cells) have nearly trebled in the last few decades, particularly among younger people. This could be because people are taking holidays in the sun and using sunbeds, overexposing themselves to radiation over short periods.