Healthy cells Help Cancers Resist Chemotherapy
A neighbor saves a tumor
Neighboring healthy cells are responsible for the mechanisms of drug resistance of tumor cellsOksana Abramova, "Newspaper.
A characteristic feature of this group of diseases is the rapid formation of abnormal cells that germinate beyond their usual boundaries and are able to penetrate into the tissues surrounding the affected area and form metastases, i.e. spread to other organs. Metastases are the main cause of death from cancer.
Statistics and forecasts of the World Health Organization are disappointing. From 1975 to 2000, the mortality rate from oncological diseases almost doubled, and if effective means of combating them are not found in the near future, it will continue to grow, and in 2030 13.1 million people may die from neoplasms.
Currently, extensive knowledge has been accumulated about the causes of cancer, measures for the prevention and management of this disease, but not all types of oncological diseases are amenable to therapy. One of the most frightening properties of cancer is its ability to return after seemingly successful treatment. Another serious problem facing doctors is the resistance of tumor cells to drugs.
A group of American scientists from the Broad Institute, the Dana-Farber Cancer Institute and the Massachusetts General Hospital made an interesting assumption: the cause of cancer relapses, as well as tumor resistance to therapy, should be sought not in cancer cells themselves, but in healthy cells inside the tumor, and in the interaction of normal and pathological tumor cells with each other.
A report on the study was published in the journal Nature (Straussman et al., Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secrecy).
Historically, cancer specialists have tried to isolate only pathological cells for their laboratory experiments, to tear them out of their natural environment. However, the Americans' research yielded an interesting result: isolated groups of cancer cells, their "pure" colonies, so to speak, died under the influence of many anti-cancer drugs, while with the coexistence of "mixed" colonies of healthy and diseased cells, the latter turned out to be resistant to more than half of the 23 drugs tested.
Based on the result of the Americans, it can be assumed with a high degree of probability that the failures of the use of drugs in the treatment of humans in conditions when these drugs proved effective in the treatment of human tumors vaccinated with animals are due to the fact that human tumor cells in the animal body, in fact, are their "clean line", torn out from their single colony of coexistence of tumor cells and surrounding human tissue.
The data obtained by scientists reflect the real picture that clinicians observe in patients with one of the types of skin cancer - melanoma. Melanoma for the study of this issue was not chosen by chance: recent developments have made it possible to make a real breakthrough in the treatment of this ailment. In particular, the experience of selective therapy aimed at combating a specific mutation in one of the human genes (BRAF), which plays an important role in cell growth. Its mutations (now more than 30 are known) lead to birth defects, as well as to the development of various types of cancer (melanoma, colorectal – colon and rectum, lung, thyroid, etc.).
Drugs are being developed for the treatment of oncological diseases caused by BRAF mutations, one of them – Vemurafenib (BRAF inhibitor PLX4032) – was approved by the U.S. Food and Drug Administration (FDA) on August 17, 2011 for the treatment of late-stage melanoma.
Despite this, only in some patients, tumors completely disappear under the influence of drugs, while neoplasms of other patients only slightly decrease in size or even do not decrease at all, and in the end drug resistance develops in almost all cases of treatment of metastatic melanoma with BRAF inhibitors.
Scientists have found that changes in individual genes are responsible for relapses (the "return" of cancer), which can give tumor cells the ability to overcome the effects of exposure to drugs over time. But such acquired resistance mechanisms cannot explain the initial resistance of tumors to treatment, which is periodically observed in patients.
This fact prompted American researchers to study the immediate environment of pathological cells and try to determine which factors most strongly influence the resistance of tumors to treatment. In particular, on the example of 34 tissue samples of cancer patients, it was found that the reduction in the size of neoplasms was significantly influenced by the level of hepatocyte growth factor (HGF), which plays an important role in the embryonic development of organs, and in adults is responsible for tissue regeneration and wound healing: tumors in patients with high levels of HGF under the influence of treatment decreased less than in patients with low levels of HGF.
Other American cancer specialists from the research institutes of San Francisco, Nashville and Los Angeles came to a similar conclusion about the significant effect of HGF levels on the resistance of neoplasms to drug therapy. Their work with cancer cells isolated from 41 human tumors was aimed at creating anti–cancer kinase inhibitors - enzymes that ensure the inclusion of glucose and glycogen in the process of glycolysis in living cells and participate in the synthesis of compounds important for the body. (Wilson et al., Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors.)
A significant result of the conducted research is that drug resistance no longer seems to be something mysterious and completely incomprehensible. To date, the way has been opened to study the mechanisms of tumor resistance to drug therapy, which allows researchers to purposefully focus their efforts on a systematic analysis of the factors and prerequisites of such resistance, and to do this much earlier than it has been practiced so far – even in the process of creating drugs.
Currently, a number of HGF/MET inhibitors are already at the stage of clinical development, testing or approval by the FDA, which, in combination with BRAF inhibitors, can and should weaken the mechanisms of resistance of malignant neoplasms to drug therapy. In this regard, there is every reason to hope that by the time some new drug reaches the stage of clinical use, the mechanisms of resistance of cancer tumors to drug therapy will already be well studied and an effective strategy for combating them will be justified and developed, which means the lives of many people saved, each of which is priceless.
Portal "Eternal youth" http://vechnayamolodost.ru09.07.2012