Despite being the primary treatment for several types of cancer, some drugs used in chemotherapy are able to “wake up” dormant tumor cells and can lead to cancer recurrence in patients, according to new research.
The action by which this occurs is the release of pro-inflammatory substances by cells adjacent to the tumor area, such as interleukins (IL-6) and cytokines, which end up causing a chain reaction and releasing dormant cancer cells. In the study, a class of chemotherapy drugs known as taxanes was evaluated, which acts by inhibiting the division of tumor cells.
Thus, researchers state that treatment with anti-inflammatory agents, such as interleukin and cytokine inhibitors, can reduce this action, preventing the proliferation of new potentially tumor cells. The findings were published this Tuesday (12) in the specialized journal PLoS Biology.
In general, patients with breast cancer, when diagnosed early, can be cured within the first few years, but local recurrence (or recurrence) can occur in approximately 6.5% of cases, mainly in the first five years after the initial diagnosis, according to data from a study by UFG (Federal University of Goiás).
Metastasis, that is, when the cancer spreads to other organs, is more frequent when the cancer diagnosis is late (from staging level three) and can appear in 25% of cases, according to the same survey .
The taxanes most used in Brazil are paclitaxel (sold under the name Taxol) and docetaxel (sold under the name Taxotere). They are mainly indicated for breast and small cell lung cancer.
To assess whether the use of taxanes can affect dormant tumor cells, scientists at Emory University carried out in vitro experiments, that is, in organoids created in the laboratory from cells modified to simulate a tumor, in addition to mice that had breast cancer. breast.
The cell lines studied contained stromal cells, which are connective tissue — the “network” that keeps other cells connected, made up of fibrocytes, fibroblasts and other cells of the immune system.
When treated with docetaxel, these cells started to release inflammatory agents, in particular interleukin IL-6 and granulocyte-stimulating factor (G-CSF), which works by stimulating the bone marrow to produce granulocytes and release them into the bloodstream.
Conversely, the release of these pro-inflammation markers was able to reverse dormant cells, acting to “wake up” new tumor cells through a repair mechanism for damaged cells.
“We discovered that docetaxel indirectly triggers the ‘awakening’ of dormant cancer by damaging stromal cells, releasing cytokines, which in turn trigger the release of dormant cancer cells by signaling the MEK/ERK mechanism,” said researcher Ramya Ganesan, of Emory University School of Medicine, first author of the study.
The thesis that inflammatory markers would be associated with the reversal of the dormancy process in cancer cells was also proven in animal models. But in them, unlike the cellular organoid, it was also possible to observe the immune response against these inflammatory markers.
“However, when administering a MEK inhibitor [anticorpo monoclonal selumetinib] together with chemotherapy, we managed to prevent the release of dormant cells. Furthermore, based on the immunological profiles in our study, we imagine that the combination of drugs [selumetinib + docetaxel] and immunotherapy could produce positive results in the treatment of cancer”, said the scientist.
According to the authors, with this knowledge they were able to act to block this immune response that is capable of waking up cancer cells. “Now, future research can look for this targeted therapy, with antibodies that are capable of neutralizing both IL-6 and G-CSF, or even a drug capable of mediating this molecular signaling in adjacent cells, inhibiting dormant cells from being released after chemotherapy”, says the article.
“That’s the hope! Despite the unwanted effects of chemotherapy, it is still widely used to attack cancer cells. Using the MEK inhibitor, which is already a clinically approved drug, along with taxane chemotherapy, would improve the effects outside of target. It can be said that this is a result of a pre-clinical trial with great potential for clinical trials,” explained Ganesan.
