Experimental drug blocks cancer-causing protein
growth of blood cells, characteristic of Myeloproliferative Disease
(MPD) reported improvement in a sufferer's symptoms raising the
possibility of an effective cancer drug treatment where mutant
FGFR1 is the culprit
PKC412, is a highly specific "targeted" drug that disables a switch in cancer cells that have become jammed in the "on" position because of genetic mutation. The thinking is since the drug blocks abnormal FLT3 and FGFR1 kinases and its resultant cancerous activities the treatment is sure to be effective against MPD, as well as other diseases and cancers including Pfeiffer syndrome.
In an additional display of the drugs potency the scientists from Dana-Farber Cancer Institute and Brigham and Women's Hospital prolonged the lives of mice with MPD that were treated with the oral compound PKC412 significantly outliving those given a placebo.
When tested in the patient, a 52-year-old woman with MPD, the drug reduced her high white blood cell count and shrank her enlarged spleen and lymph nodes. However, the disease wasn't cured and she underwent a bone-marrow transplant to treat the acute leukaemia caused by her MPD.
MPD is caused by a different mutated kinase, FGFR1. The mutation occurs when two broken pieces of the chromosome that carries the FGFR1 gene join together abnormally. This blood disorder allows a continuous stream of signals to produce blood cells into an uncontrolled frenzy of division and growth. The overproduction of white blood cells in MPD damages organs and generally turns into an acute leukaemia that can be fatal.
Richard Stone, senior author of the study, said: "The study shows the potential utility of drugs that block mutant tyrosine kinases, and that these drugs are opening more doors to treating cancers."
Tyrosine kinases are molecules that act as biological switches inside cells, regulating processes including cell division and growth. Abnormal kinases have been discovered to be major culprits in many forms of cancer. Because inhibitor drugs strike the abnormal kinases in cancer cells without harming normal tissue, they are associated with fewer side effects than standard cancer drugs.
PKC412 could be seen as a natural successor to Novartis' Gleevec (imatinib), one of the first drugs to treat cancers by shutting down abnormal kinase signal switches. Gleevec blocks uncontrolled growth signals in Chronic Myelogenous Leukemia and Gastrointestinal Stromal Tumour.
Gleevec specifically targets c-Kit kinase, along with another related enzyme known as c-Abl kinase.
