Prochlorperazine (PCZ) is a drug used for psychiatric use and the therapeutic treatment of nausea but was recently found to block the internalization of molecular receptors on the surface of tumor cells allowing more effective anticancer antibodies to avoid immune evasion.
"This represents a potentially disruptive change in clinical approaches to improve therapeutic targeting as the opportunity of temporarily moving drug targets within patient tumor cells becomes possible," says senior author Fiona Simpson, a cancer researcher at the University of Queensland.
PCZ was used as the temporary treatment of cancer in some patients and results yielded receptor clustering inside cancer cells of patients. Findings were published in the journal Cell.
"These findings highlight the crucial role of availability and persistence of the molecule targeted by the therapeutic antibody at the cell surface of tumor cells," Simpson says.
PCZ is also used in laboratory studies to inhibit a cellular process known as endocytosis—a mechanism that brings outside substances to the inside of the cell. Such inhibition has held clinical relevance for the control of viral infection.
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To apply the mechanisms of PCZ, researchers analyzed tumor samples from patients and found a decrease in endocytosis of a protein known as epidermal growth factor receptor (EGFR). The particular protein was found to be inhibited by a cancer therapeutic called cetuximab.
"We found that if we stopped the drug targets getting inside the cells by inhibiting the uptake process, called endocytosis, we got a really big immune response against the tumors in mice," Simpson says. "This led to the concept that temporarily halting endocytosis of receptors that are the targets of monoclonal antibody therapies may be used to improve clinical outcomes.”
Source: Science Daily