01 December 2017

Improving the effectiveness of radiation therapy

The drugs that are currently under development can be used to treat neoplasms that do not respond to radiation therapy.

In a new study, an international team of scientists led by Ralph Weichselbaum from the University of Chicago has discovered an immune mechanism for the formation of resistance to radiation therapy.

The tactics of treatment of tumor diseases is determined by the doctor individually, depending on the type of tumor, the stage and course of the disease, the general condition and age of the patient.

There are three types of radiation therapy: contact, in which the radiation source is directly attached to the tumor, remote, in which the source is not in contact with the patient's body, and systemic (radionuclide), in which a radioactive drug is injected into the patient's blood.

The authors of the study write that radiation therapy as the only method of treatment or in combination with other methods is prescribed for 50-60% of oncological diseases. In 40% of these cases, resistance develops: the tumor does not respond to radiation in any way and continues to progress. Finding ways to overcome this resistance is extremely important for patients, especially those for whom radiation therapy is the only possible method of treatment.

It is known that radioactive radiation induces inflammation by activating a signaling pathway that stimulates interferon genes (stimulator of interferon genes, STING).

STING activation has both positive and negative effects.

On the one hand, the cells of the immune system attack the tumor, as the STING system allows you to detect atypical cells. There is an active production of type 1 interferons, which "indicate" to T-killer lymphocytes their target – tumor cells. The growth of the tumor stops.

On the other hand, increased production of type 1 interferons induced by STING leads to an active influx of myeloid suppressor cells. These cells suppress the immune response.

In mouse models with colon and lung tumors, STING was found to activate the CCR2 protein on the surface of myeloid suppressor cells.

The role of the CCR2 protein was determined by comparing tumor dynamics in wild-type mice and animals with the CCR2 gene knocked out. The absence of this protein was associated with less resistance of the tumor to radiation therapy.

In another experiment, administration of CCR2-blocking antibodies to mice also reduced the tumor's resistance to radiation therapy. This finding can be used to develop drugs to increase the effectiveness of radiation.

The researchers also found that the greatest effect of radiation treatment of the tumor was observed when a STING-activating drug was administered simultaneously with an anti-CCR2 drug. The first enhanced the immune response, the second prevented its suppression.

The authors believe that the results of their study are applicable not only to radiation therapy, but can help increase the effectiveness of chemo- and immune therapy of neoplasms of various localization.

A drug that activates STING has already been developed. It is being investigated as an adjunct to immunotherapy. In addition, some anti-CCR2 drugs are under development.

The authors believe that their research has made it possible to take a step towards increasing the effectiveness of radiation therapy for solid tumors.

Article by Hua Liang et al. Host STING-dependent MDSC mobilization drives extrinsic radiation resistance is published in the journal Nature Communications.

Aminat Adzhieva, portal "Eternal Youth" https://vechnayamolodost.ru according to Medical News Today: Radiotherapy-resistant tumors could be defeated with experimental drugs

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