On the Path towards an individualised Cancer Therapy

The genome is the genetic material stored within the nucleus of every cell, consisting of a sequence of 3.2 billion DNA building blocks. In 2003, an international research team delivered the completely decoded human genome and thus completed the work on the human genome project begun in 1990. Now, German researchers have joined a new mammoth project of biomedical genome research.

The International Cancer Genome Consortium resolved to reveal the entire range of differences between the genetic material of normal cells and of cancer cells. The goal is a list of all genes the mutation of which advances cancer growth. It is planned to analyse probes from 500 patients each for 50 tumour types. Since the comparison requires also the genetic material sequences of each patient’s healthy cells, this results in a total data base of 50,000 genomes, an immense amount of data surpassing anything done in biomedicine to this day. The German Cancer Research Centre (DKFZ) in Heidelberg functions as the central point of contact for the German institutes involved. Professor Dr. Peter Lichter, Head of the Division “Molecular Genetics”, is the coordinator of the national research alliance. His deputy Professor Dr. Roland Eils, Head of the Division “Theoretical Bioinformatics”, takes on the management of the flood of data.

A project of this magnitude requires international collaboration, for without a doubt it would overextend the financial and personnel capacities of national research. The involved institutes from each country concentrate on one or just a few tumour types each. For instance, the Chinese researchers took over stomach cancer, whereas Japanese and French institutes decided to do one type of liver tumour each. The German researchers are going to analyse two kinds of the most common brain tumours in children, medulloblastoma and pilocytic astrocytoma. Each year, around 300 children in Germany develop this type of cancer. “For these types of tumours there already exist preliminaries and a comprehensive collection of tissue probes at the DKFZ”, says Peter Lichter. This project, scheduled to run over five years, receives financial support of 15 million Euro from the Deutsche Krebshilfe e.V. (German Cancer Aid) and the German Federal Ministry of Education and Research. By now, first gene analyses of brain tumour probes have begun within the context of the German “PedBrainTumor” Consortium. New probes are supplied predominantly via a network of German oncologists.

Until recently, cancer researchers assumed that less than ten changed genes are sufficient to effect uncontrolled cell growth. But then first genome analyses of chest and intestinal tumours revealed that in cancer cells at least 20 relevant genes are mutated. The new large-scale project is to find out how many such cancer genes there are – over 300 are known already.

Each tumour type could then be characterised by a typical profile of cancer genes and be allocated to a subtype. “Yet this genetic classification aims not to substitute the existing tissue typology but augment it”, stresses Lichter. Hence, the complete sequencing of each probe’s genome is compulsory. If possible, additional information regarding the gene activities is to be collected. It is also intended to find out, which genes of cancer cells are activated or inactive and what kind of micro RNAs are formed. Micro RNAs are small nucleic acids playing a part in gene regulation. Cancer patients will directly profit from the research programme’s results in various aspects: On the one hand, diagnostics are improved, since the pattern of all cancer genes known by then will reveal the subtype of a tumour in much greater detail than before. At the same time, this facilitates choosing the best suited therapy. For instance, rapidly growing, aggressive forms of tumours call for a different therapy than less dangerous types. On the other hand, the verification of new genetic characteristics of cancer can improve early detection or yield information whether available cancer medication is effective or not. Severe side effects and longterm consequences of ineffective treatment could thus be avoided. Last but not least, hitherto unknown cancer genes could reveal new target structures leading towards the development of entirely novel forms of medication.

As yet, sequencing the cancer genome for application in routine diagnostics would be too expensive. “The mere running costs for sequencing a genome are between 8,000 and 10,000 Euro these days”, states Lichter. However, it would not be unrealistic for these costs to soon be reduced to under 1,000 Euro. Then each cancer patient could be offered a complete genetic material analysis of his or her tumour. And this would be a great step towards the aim of individualised cancer therapy.