Targeted therapy or personalised medicine for treating Acute Myeloid Leukaemia (AML), a type of cancer, got closer to reality — thanks to an important breakthrough achieved by a group of scientists at the University of Virginia, U.S.
Around 3,50,000 new cases of leukaemia are reported each year worldwide. AML is a type of cancer affecting bone marrow and blood cells and less than 25 per cent survive for more than five years in adult AML cases.
Like in many other cancers, AML too is caused by genetic changes at cellular level. These changes result in production of fusion proteins, transcription factors and lead to growth of abnormal leukaemia cells. Transcription factors which bind DNA and regulate gene expression play a key role in triggering such abnormal cancerous cells.
One such transcription factor fusion known as CBFβ-SMMHC, expressed only in AML, was targeted by a drug developed by group of scientists at the University of Virginia, including Prof. John Bushweller and Dr. Anuradha Illendula.
The scientists blocked the binding of CBFβ-SMMHC to another protein, RUNX1. Once that was done, the normal RUNX1regulation started and the oncogenic process was stopped.
According to Dr. Anuradha, the drug inhibits CBFβ-SMMHC fusion protein, which drives leukaemia and not the normal CBFβ protein. The drug developed was very specific for this type of leukaemia, she added.
Describing it as a ‘major breakthrough’, she said the drug was found to be quite effective in mice transplanted with AML as also in human AML samples. She said leukaemia was introduced into a mouse model and the disease was found to be cured after giving the drug. Similar results were found in a human blood sample.
Pointing out that personalised medicine seeks to use very specific drugs to target select set of disease-causing proteins in certain groups of individuals,
Dr.Anuradha said the specific drug targeting of CBFβ -SMMHC was an example of strong potential for personalised medicine. It also opens new avenues for drug development to target transcription factors, “which are undruggable”, she added.
She said their finding was already patented and negotiations were underway with companies to license the drug for subsequent steps needed for application in humans.
The work of the scientists was published in February, 2015 issue of Science.
