Stop and block
The drug can prevent cancer metastases
Lina Medvedeva, XX2 century
"There is no more tumor" – the words that people hope to hear after surgery. But with the growing understanding of how cancer spreads and metastasizes, it turns out that not only are they almost never true, but most likely a more effective way of treatment is to try to contain cancer rather than eliminate it.
The new approach tested on animals was called lock'n'block (stop and block). A group of scientists led by researchers from Purdue University has discovered that a drug already on the market for use in another field can be used in therapy to prevent metastasis of breast cancer. Article by Shinde et al. Spleen Tyrosine Kinase–Mediated Autophagy Is Required for Epithelial–Mesenchymal Plasticity and Metastasis in Breast Cancer published in the journal Cancer Research.
Associate professor of the Department of Medical Chemistry and Molecular Pharmacology Michael Wendt, says that cancer researchers are beginning to realize that they are pursuing an impossible goal.
"Most cancer therapy is aimed at killing all cancer cells. Destroy the cancer body. But recently there have been a lot of studies showing that we will never be able to do this. Cancer cells develop so fast that they always find a way to avoid any kind of therapy," says Wendt. – The new concept of cancer treatment is that we should try not to kill all cancer cells, but to keep them in a weak state that does not cause any symptoms. In a state of inactivity."
Wendt led a joint study, during which it turned out that the drug fostamatinib is an effective means of blocking and containing metastatic cancer cells in mice.
Aparna Shinde, a researcher at AbbVie Inc., says that the study focused on breast cancer because it is often what leads to metastasis after a few years.
"If a patient had breast cancer, it always leads to the spread of cancer cells," she says. – Breast cancer is not considered a curable disease, it is a chronic disease, because after 10 or 20 years, secondary tumors can be obtained due to metastatic cells. But we have shown that we can block cells so that they are in a dormant state. Even if the patient has metastases, we can keep them in this state for a very long time."
Wendt explains that when cancer cells move from the primary tumor to another part of the body, they can be dormant for many years. Cancer cells are very resistant to current drug therapy because existing drugs are designed for cells that grow faster than normal cells, at the same rate as cancerous tumors. But this does not apply to cancer cells scattered throughout the body, which can be dormant for many years.
"We are now studying these scattered cells. They can be kept in a dormant state instead of trying to eliminate them," says Wendt.
The researchers used the drug fostamatinib because it inhibits a specific protein, non-receptor tyrosine kinase (SYK), found in scattered cancer cells.
"This is a significant discovery for us, because it is a drug with low toxicity. It is intended for people with chronic diseases, they can take it for a long time," says Wendt. – We believe that fostamatinib is an ideal candidate for the long–term effects of lock'n'block (stop and block). It is suitable for further research and finding out whether it is possible to stabilize cancer cells in a dormant state. If SYK manifests itself in other oncological diseases, this may apply to them as well."
In the current study, scientists surgically removed a breast cancer tumor from mice. The tumor cells were labeled with luciferase, a bioluminescent firefly protein that allows researchers to track and quantify the level of metastatic cells.
The researchers found that the cancer cells treated with fostamatinib remained dormant and did not cause metastases in other parts of the body.
"Our work is unique in that it is one of the few works in which metastasis therapy was tested in postoperative conditions. Most of the research focuses on the treatment of the primary tumor. We are targeting later disease processes to see if we can keep tumor cells dormant," Wendt said. – But clinical trials of this kind of thing are very difficult, since patients are formally in remission. We suspect that in such patients dormant cancer cells are spreading through the body, but we have no way to detect them right now."
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