A combination of molecules that freed themselves only in the presence of cancer operates an alarm system of the immune system at the most appropriate time.
“Activate only in case of need”: a two -stroke drug, which begins to work only in the presence of a tumor, promises to awaken in a more prudent way and therapeutic purposes a powerful immune alarm mechanism already naturally present in the human body. The discovery, on Nature Chemistrywill help to avoid dangerous side effects of therapies that exploit this line of defense to treat cancer.
An internal alarm siren to the cells
The research refers to a signaling way, that is, to one of those communication processes that regulate and coordinate the basic activities of the cells, called Cgas-Sting, which has an indispensable role in innate immunity, the first defensive barrier against viruses and bacteria. When this signal is activated in cancer cells, the components of the immune system are led to tie in the area where the tumor has developed and attach the sick cells.
Some drugs can activate this path of signaling, but not without contraindications: if by mistake the alarm “sounds” in healthy cells, there is the risk of serious side effects.
Drugs caged but ready for action
To remedy the problem, a group of chemists from the University of Cambridge (United Kingdom) has conceived a system of proparma – i.e. biologically inactive molecules, which are activated only if introduced into the body and in particular conditions – in two times. The first component remains “closed”, inert, until he meets an enzyme product in a specific and massive way in cancer sick cells, beta-glucuronidase. Only when the molecule finds these enzymes within a tumor is the second component activated and activated in a waterfall.
Together, these two closed “packets”, which open quickly and selectively only in the presence of cancer, constitute a powerful activator of the CGAS-Sting reporting route. In the laboratory, tested on zebrafish and specially engineered mice to produce β-glucuronidase, the two components have formed an active compound that managed to operate Sting even in very low concentrations and almost exclusively in the presence of cancer, saving the vital organs from the inflammatory reaction.
The new design will help to refine the therapies based on the CGAS/Sting signaling route, which have so far struggled to distinguish healthy fabrics from those affected by cancer. But the mechanism could inspire new classes of precision drugs, made of separate components that are activated only in presence and on the disease site: a particularly useful capacity when there is a need for powerful drugs to be delivered safely.
