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| Why is cancer still one of the major threats of modern life? |
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There are several reasons known. Probably one of the most common is the ageing of the population. Age is a cause of cancer. But we have to admit that primarily it is because we failed in prevention and therapy. In our Institute, the Swiss Institute for Experimental Cancer Research (www.isrec.ch), we are looking for ways to improve therapy and are not involved much in prevention. |
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| What are the chances of surviving cancer today? And how much better would they be if the research in your institute was successful? |
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Cancer is of course not one disease. It is a very heterogeneous group of diseases and they all behave quite differently. However, they have some common traits, which is uncontrolled cell division and an abnormal behavior leading to metastasis. In an industrialized country, about one third of the population is going to be affected by one form of this disease. In roughly half of these cases, the disease will be the cause of death. But this varies a lot between different types of cancers. |
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| What happens in the cell when someone develops cancer? |
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Cancer is a genetic disease in which multiple genetic defects accumulate over time. These defects generally result in the over-activation of pathways which stimulate cell proliferation or in the loss of signals which inhibit cell division or induce cell death (apoptosis). |
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| How common is colon cancer? Is this a major threat for people today? |
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In man it is third after lung and prostate cancer, and in women it is actually the second after breast cancer. So it is a very frequent tumor. Unfortunately, women are catching up in lung cancer. So, overall it is certainly the third most common tumor. |
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| Will Prof. Baslers' research have an impact on modern cancer research? Will it allow new approaches in drug design? |
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Absolutely. The signaling pathway that Professor Basler is dissecting using Drosophila genetics is common to almost all colon cancers. This is a relatively unusual situation. As I said, cancers are very heterogeneous diseases and even within a certain group of cancers, like for example breast cancer, they are still very heterogeneous. In colon cancer we have the particular situation where in most cases the same pathway is activated. Thus, if this pathway can be inhibited, such a therapy should work for the majority of colon cancers. |
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| Professor Basler identified two new cancer genes in Drosophila. Can research using the fruit fly tell us something relevant for human medicine? Why can it be assumed that the corresponding human genes play an important role? |
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One of the most impressive findings of genomics, the comparison of the complete sequence of all the genes of various organisms, is the observation of a remarkable degree of conservation of genes and biochemical signals. Knowing that, one will choose the simplest existing model to study these signals and not start with complex system such as human cells. Genetic approaches, including the identification of many cancer related genes trough human genetics have contributed the most remarkable discoveries in cancer research. The fact that signaling pathways are conserved, allows us to use models which are genetically tractable such as Drosophila. |
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| Do you know of another drug that is based on trying to correct deregulated gene expression? Has something like this been proven successful before? |
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There are now many efforts going on to inhibit signaling pathways just like the pathway that Professor Basler is working on. For example, in several tumors a receptor, the so called epidermal growth factor receptor, is overactive and stimulates cell proliferation. The pathway stimulated by this receptor is now a target for inhibitory drugs that are currently explored in the clinic. Thus, the concept of blocking a pathway which is over-activated in tumors has already been proven. |
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| A drug developed on the basis of the two new genes would aim at changing the defective regulation of genes in colorectal cancer cells. Can you imagine any side effects such a drug could have? Or would it be one of its advantages that it is very specific? |
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This pathway has a normal function and is not just over-acting in tumors. So, if it is blocked completely, yes, one would expect side effects in tissues where the pathway is normally needed. In this case only few tissues are expected to be affected, such as certain stem cells in the adult. On the other hand we have many in part similar side effects with other cancer therapies as well, so I think this is not a major concern. In addition, as this pathway is over-active, it might not be necessary to block it entirely, but sufficient to reduce its strength and still have a beneficial effect on the tumor. Eventually, it is a dosage effect, as with any drug. |
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| It seems that the more we understand the more specific the drugs we are able to make are. Is this true? Do we nowadays have drugs with less side effects than in the past? |
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Yes. It depends on the normal effect of such a pathway, but in general that's right. The more we know about a pathway, its normal role and the consequences of its abnormal regulation in a tumor, the more specifically we can intervene to exploit the difference between a normal cell and a tumor cell, and the less side-effects we will have. |
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| How long does it take to develop a new drug starting from basic research results as in this case? |
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There we have to be very cautious. I think the major progress that we have seen is in improving the specificity of new treatments. It's very clear that the more we know, the more effective we are going to be. Whether we will be fast ... just look at the clinical development, the trials that are needed to assess the efficacy of a drug. We are not going to be able to shorten that dramatically. However, maybe we are progressing faster now in terms of translating ways to apply basic research results in drug development. This could accelerate the process. The process of discovering and developing new drugs will still take a long time, but it will become more efficient. We will see many new targets and many more strategies to target tumors.
If you take simple examples like the growth factor receptor we were talking about, it still took 10 years from the discovery of that mechanism until first new drug become available on the market. |
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More information on colon cancer:
Colon Cancer Talk at the Gastrointestinal Cancer Meeting 2000
Esophagus & Gastrointestinal Tract Illustrations
National Colorectal Cancer Research Alliance
The John Hopkins Medical Institutions on Colorectal Cancer |
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