Arthritis Drugs Help in Cancer Treatment
Some aggressive malignant neoplasms
may respond to anti-inflammatory medications
sci-lib based on ScienceDaily: Some aggressive cancers may respond to anti-inflammatory drugsThe results of another study suggest that some patients who have aggressive tumors may benefit from a group of anti-inflammatory drugs used to treat rheumatoid arthritis.
Studying breast cancer with a triple negative phenotype, the staff of the Washington University School of Medicine in St. Louis found that some aggressive tumors use an antiviral metabolic pathway activated for the development of inflammation. This metabolic pathway is known for the functions it performs in the development of cancer, rheumatoid arthritis and other inflammatory diseases. Tumors that activate this antiviral pathway always carry inactive forms of p53 and ARF proteins. These proteins are encoded by genes that are known to mutate strongly in cancer tissue cells. The authors of the study found that these two genes compensate for each other. If both of them are changed as a result of mutations, the tumors that form are more aggressive than if only one of these genes stopped functioning as a result of mutations.
When both genes are inactive and the antiviral pathway mentioned above is activated, a group of drugs called JAK inhibitors can help patients. They are prescribed for rheumatoid arthritis.
Until now, even though it was known that ARF is expressed in some tumors carrying the mutant form of p53, it was assumed that ARF does not perform any functions under these conditions. But scientists have shown that in the absence of p53, ARF protects against the formation of more aggressive tumors.
The photo shows the mammary gland of a mouse in which p53 is not expressed.
ARF expression is visible (areas highlighted in green).
"It may not be entirely correct to say that ARF completely replaces p53, an effective tumor suppressor that uses different ways of working. But it seems that the cell has created something like an ARF-based backup system. It is not surprising that these tumor suppressors change significantly as a result of mutations in the development of cancer. Since they duplicate each other, the most aggressive tumors form when you lose both of them," says Jason D. Weber, senior author of the study, associate professor.
Weber and his colleagues chose to study breast cancer with a triple negative phenotype, since it often mutates simultaneously p53 and ARF. Breast tumors with a triple negative phenotype are treated surgically, with the help of chemo and radiotherapy. This is due to the fact that targeted therapies, which are usually used to treat hormone-dependent breast malignancies, are ineffective.
Scientists have shown that in most tumors with a triple negative phenotype, the absence of p53 and ARF triggers a metabolic pathway involved in the innate immune response to viral infection.
"This is not the level of activation that you could observe with a real antivirus response, it is higher than normal. We are interested in studying whether this antiviral response creates a local environment of inflammation that supports more aggressive tumors," says Associate Professor Weber. According to him, JAK inhibitors are prescribed for rheumatoid arthritis. In addition, they are tested for suitability for use in the treatment of a number of other diseases.
"Our data confirm that these anti–inflammatory drugs can be used as a treatment for some patients in whom p53 and ARF do not work," says Associate Professor Weber.
These drugs may benefit patients who have inactive p53 and ARF. In the event that either p53 or ARF is active, the antiviral pathway in question is inactive, that is, it does not participate in tumor growth.
A more detailed description of the results of the study can be found in the journal Cell Reports (in the public domain):
Forys et al., ARF and p53 Coordinate Tumor Suppression of an Oncogenic IFN-b-STAT1-ISG15 Signaling Axis.
Portal "Eternal youth" http://vechnayamolodost.ru30.06.2014