Big Pharma is becoming adept at identifying new uses for old drugs. Companies are re-examining established therapies – conducting refocused clinical research within the relatively new context of genome mapping. With increasing clarity, we are able to see how drugs impact cell behavior and operations, and this ability is yielding promising results in the treatment of various forms of cancer. Recent research out of Boston has revealed that a 50 year old antipsychotic medication called perphenazine may be called back into active duty – this time to battle acute lymphoblastic leukemia (ALL), a particularly aggressive form of cancer.
The research results
To identify possible new treatment options, the research team screened a library of 4,880 compounds – including FDA-approved drugs whose patents had expired, small molecules and natural products. The scientists were focused on findings drugs that could be used against ALL, even if they had not previously been designed to target the disease. Dr. Look, one of the lead researchers explained, “there may be drugs available for other indications that could be readily repurposed if we can show activity.” And perphenazine emerged as a top contender, demonstrating anti-leukemic potential in several mouse and human ALL cell lines. The drug, originally meant to control anxiety, depression and bi-polar disorder has a unique ability to shut down cancer cells.
How does it work?
Perphenazine works by turning on a cancer-suppressing enzyme called PP2A, which causes malignant tumor cells to self-destruct. Dr. Gutierrez, co-leader of the study, underscores the novelty of the discovery, explaining that “”we rarely find potential drug molecules that activate an enzyme…most new drugs deactivate some protein or signal that the cancer cell requires to survive.” The research has led to new knowledge about PP2A- activating drugs, which the study team believes could be used to combat a range of cancers. According to the scientists, many tumors contain proteins that would be vulnerable to the action, and research is underway to study how drugs like perphenazine impact various malignancies.
Future prospects
Dr. Gutierrez and Dr. Look, along with their collaborators, are now working to better understand the interactions between PP2A and perphenazine. They also want to indentify molecules that bind to and activate the enzyme more tightly, while avoiding perphenazine’s psychiatric effects. The drug will undergo typical pharmaceutical quality assurance measures as researchers develop its new capabilities. Students in pharmaceutical courses and professionals in the field understand that as the cost of drug development and testing sky-rocket, the industry turns to recycling drugs, seeking ways to reinvent their therapeutic profiles. Applying new knowledge to old compounds, Big Pharma has hit upon an increasingly cost-effective way of developing much needed new treatments.
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