All cancer genes in one database
Encyclopedia of Cancer
The goal of cancer treatment research is to identify the target that needs to be hit in order to defeat the disease, and to find the right medicine that affects exactly this goal. However, there is a long way to go before such "personalized" medicines are developed. Precise knowledge is needed about the genetic variations that cause a particular type of cancer, as well as about their sensitivity to possible therapeutic agents. And to do this, it is necessary to combine the efforts of all researchers by creating a publicly accessible database of information already received.
Two works of this kind were made by scientists in collaboration with representatives of the pharmaceutical industry.
Scientists from Harvard University and the Massachusetts Institute of Technology, together with Novartis, presented the first results of work on a publicly available resource that combines data on the cancer genome and data on suspected effective drugs. This information can not only provide data for the development of new treatments, but also improve existing technologies.
"We hope that the Cancer Cell Line Encyclopedia will become a preclinical source that will guide clinical trials," said Harvard Medical School professor Levi Garraway, one of the lead authors of an article in the journal Nature on the encyclopedia (The Cancer Cell Line Encyclopedia enables predictive modeling of anticancer drug sensitivity).
The encyclopedia combines data on gene expression, chromosome number and genome sequencing for almost a thousand human cancer cell lines, as well as a complete pharmacological profile of 24 anti-cancer drugs and a description of their effect on almost half of the above-mentioned cell lines. Currently, about 1,200 cancer cell lines are commercially available, but experts have selected 947 of the most representative for the disease.
"One of the strengths of the encyclopedia is the number of cell lines covered. It allows us to extract sufficient statistical information even for rare cancers," emphasizes one of the authors of the work, Nicholas Stransky.
Cell lines are malignant tumor cells that have been selected from the patient's diseased tissue and cultured in the laboratory. Under certain conditions, they can multiply indefinitely. This "near-immortality" is useful for repeated experiments, but there is always a risk that the cells in the new generation will already change compared to those taken from the tumor, as they will be deprived of the usual environment.
To avoid this, the encyclopedia included only those cell lines for which it was shown that each generation sufficiently repeats the previous one.
About 50 thousand molecular and genetic markers were generalized and systematized for these cells. From them, the factors were identified, with the help of which it was possible to predict the sensitivity of the tumor to drugs. The fidelity of each of them was then confirmed systematically throughout the sample. Based on this, drugs were theoretically suggested that would be effective for new types of cancer, the treatment of which has not yet been worked out.
For example, a number of cancers are characterized by a mutation in the RAS gene, which activates signaling pathways important for tumor growth. Some types of such cancers, including a number of melanomas, can be treated by blocking the MEK protein, also involved in these signaling pathways. The generalization of the data made in the encyclopedia allowed the researchers to identify about 40 cell lines carrying this mutation and check whether drugs that inhibit MEK act on them. Some of them are currently undergoing clinical trials.
The researchers found that cancer cells sensitive to MEK inhibitors have high levels of the AHR receptor. Thus, the sensitivity of a particular cancer to MEK inhibitors can be determined by the level of this receptor. Armed with this knowledge from the encyclopedia, scientists have a better understanding of which tumors are most likely to be sensitive to each specific drug even before clinical trials begin. Accordingly, patients can be selected for testing not randomly, but based on the molecular and genetic characteristics of their disease.
"Having these data initially, scientists have a much better chance of developing a successful drug than with a traditional "random" search, when the drug is tested on a wide range of patients with advanced cancer without taking into account the genetic profile of the disease," Garraway stressed.
Generalization of the data made it possible to find new markers of sensitivity of various forms of cancer to other already existing types of chemotherapy. The creators of the encyclopedia emphasize that this is only the first volume: others will follow.
"This is really just the tip of the iceberg. By connecting predictive modeling algorithms and broader data sets, you can get a huge amount of useful information. Perhaps these works will become an independent branch of our science," the authors of the article believe.
The authors of another paper published in Nature (Systematic identification of genomic markers of drug sensitivity in cancer cells) examined more than 600 cell lines for 130 drugs. They found that genome changes associated with Ewing's sarcoma (a rare form of cancer that has been manifested since childhood) respond to a group of pharmacological agents called PARP inhibitors. Thus, these agents may be useful in the treatment of Ewing's sarcoma.
Both of these studies provide a closer look at a person's genetic predisposition to cancer.
These works in Nature represent one of the new approaches to cancer treatment, which were discussed in his lecture in the Newspaper the day before.Ru" was told by Professor Larisa Akulenko, head of the Department of Medical Genetics of RGMSU.
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29.03.2012