Chemotherapy does not work on "dormant" breast cancer cells, which are cells that have ceased dividing and are only hidden in the body, according to a long-held belief among oncology researchers. However, such dormant cancer cells could suddenly become active and spread dangerously.
According to an article on the center's website, Cyrus Ghajar, Ph.D., head of Fred Hutch's Laboratory for the Study of Metastatic Microenvironments, stated, "It's always been assumed that dormant cells cannot be killed by any kind of chemotherapy because they're not dividing." However, we're demonstrating that to be untrue. They are dependent on the survival signaling in their microenvironment, namely the blood vessels seen in the bone marrow in this instance. Additionally, you can make them more sensitive to chemotherapy if you can block that signaling.
Researchers at the Fred Hutchinson Cancer Research Center claim to have discovered a way to stop dormant breast cancer cells from ever awakening. The secret is to interfere with a blood vessel communication mechanism that keeps the cells safe while they are asleep. Furthermore, scientists discovered two substances that have the ability to block this protective signaling and make the dormant cells susceptible to chemotherapy. Their research was published in the journal Nature Cell Biology.
Ghajar's group concentrated on estrogen receptor-positive breast cancer, which is thought to return in 17% of cases in individuals with early diagnosis. Their goal was to create a medication that would target dormant tumor cells in order to stop metastasis.
Thus, scientists started by giving chemotherapy to mice models of breast cancer and looking for dormant cells in their bone marrow. They found that some sleeping cells, despite being surrounded by microscopic blood arteries, survived the chemotherapy blast. Nonetheless, the chemotherapy did have an effect on the latent cells that lacked blood vessels.
Subsequently, they examined both kinds of quiescent cells, utilizing RNA sequencing to examine active genes. They found that the blood arteries shielding the sleeping cells from the elements were full with chemicals known as integrins, which attach to proteins. They then began experimenting with integrin-inhibiting substances until they discovered two that, when coupled with chemotherapy, effectively killed the dormant cells.
Ghajar's group's next task is to make human-safe versions of the integrin inhibitors that were employed in the experiment. In three to five years, he aims to have chemicals ready for human testing.
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