A "blocked-blocked" drug can prevent cancer from metastasizing

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<div data-thumb = "https://3c1703fe8d.site.internapcdn.net/newman/csz/news/tmb/2019/locknblockdr.jpg" data-src = "https://3c1703fe8d.site.internapcdn.net/ newman / gfx / news / hires / 2019 / locknblockdr.jpg "data-sub-html =" A new approach to breast cancer could prevent cancer from reappearing years later A research team led by scientists Purdue University has identified a drug that does not kill metastatic cancer cells, but keep them in a state of early, non-threatening development, according to a technique that researchers call "blocking blockages." The research appears on the cover of the report. this month's issue of the scientific journal Research against cancer. Credit: Courtesy of Purdue University Research against cancer">

"They understand it all" are the reassuring words that people hope to hear after a cancer operation, but a growing understanding of the science of cancer spread and its metastases indicates that not only is this almost never true, but a surprising part – it might be better to try to contain the cancer than to eliminate it.

The new approach, which at this stage has only been tested on animal models, is called "blocking", and a national team of scientists led by researchers at Purdue University discovered that a drug already on the market another use is very promising as a therapy to prevent breast cancer from metastasizing.

Michael Wendt, an assistant professor of medical chemistry and molecular pharmacology, explains that cancer researchers are beginning to realize that they are pursuing an impossible goal.

"Most cancer treatments have the goal of killing all the cancer cells – getting rid of the body of cancer, but recently, many studies suggest that we will never be able to achieve that." Cancer cells are evolving so quickly that they will always find the way to overcome any type of treatment, "said Wendt. "An emerging concept in cancer treatment is that we should not be trying to kill all the cancer cells, but trying to keep them in a low state that does not cause any kind of symptoms. want. . "

Wendt led a multi-institutional study that identified a drug – fostamatinib, sold under the brand name Tavalisse – that has been shown to be effective in mice that block and contain metastatic cancer cells. The research was recently published in the journal Research against cancer.

Aparna Shinde, a researcher at AbbVie Inc. and a former graduate student in Purdue's Department of Medicinal Chemistry and Molecular Pharmacology, said the research was about breast cancer, because it is particularly well-known for leading to the metatization of cancer over the years. later.

"After breast cancer, you still get this spread of cancer cells," she said. "Breast cancer is no longer considered a treatable disease, it is now considered a chronic disease, because 10 to 20 years later, you can develop secondary tumors because of metastatic cells.

"But now, we have shown that we can block these cells in the dormant state, so even if a patient had these cells in metastasis, we could keep them in that state for a very long time."

Wendt explains that when cancer cells leave a primary tumor to move to another part of the body, they may experience a form of dormancy or latency for many years. These cancer cells are highly resistant to current drug treatments, as current drugs are designed to target cells that grow faster than normal cells, as do tumor cells. This is not the case of these disseminated cancer cells, which can remain dormant for many, many years.

"So that's the goal we're exploring now, instead of trying to eliminate those scattered cells, how can we keep them in that state of sleep?" Wendt said.

The researchers used fostamatinib because it inhibits a particular protein, the tyrosine kinase of the spleen (SYK), found in these disseminated cancer cells.

"It's great for us because it's a little toxic drug. It is designed for people with chronic diseases so they can take it for a long time, "said Wendt. "Thus, we believe that fostamatinib is an ideal candidate for this type of approach that lasts several years.We think it's a good candidate to do a clinical trial to see if we can stabilize dormancy. If SYK is expressed in other cancers, it could also apply to them. "

In their current study, researchers surgically removed breast cancer tumors in mice. The tumor cells were labeled with luciferase, the firefly bioluminescent protein, which allows researchers to track and quantify the level of cell metatization.

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 because there has been little research on treatment in a post-surgical metastatic setting, and most research is focused on the treatment of the primary tumor." We seek to target the subsequent processes of the disease in order to see if we can keep the tumor cells in their dormant state, "said Wendt. "But you can imagine that clinical trials for these kinds of things are going to be very difficult because technically patients are in remission and are without disease, we think that these patients have cancer cells spreading through their bodies. But we do not have a way to detect those right now. "