Breakthrough

Simple Summary

Press Release

Researchers at the University of Glasgow’s Institute of Cancer Sciences have been awarded £3.1 million by Cancer Research UK to lead a first-of-its-kind pioneering study to help find new treatments for patients with difficult to treat CML. The trial will study whether a combination of TKI + another drug will kill stem cells in CML. It is based on groundbreaking work by the team in Glasgow led by the late Prof. Tess Holyoake which studied quiescent stem cells in CML. 

Over the last two decades, targeted therapies like imatinib (Gleevec®)and trastuzumab (Herceptin®)—drugs that target cancer cells by homing in on specific molecular changes seen primarily in those cells—have also cemented themselves as standard treatments for many cancers.

The antibiotic tigecycline, when used in combination with current treatment, may hold the key to eradicating chronic myeloid leukaemia (CML) cells, according to new research. ‌

The University of Glasgow led study, published today in Nature Medicine, demonstrates the effectiveness of combining tigecycline with the drug imatinib – a tyrosine kinase inhibitor (TKI) and standard first-line treatment of patients with CML.

Researchers at centres in the US and Scotland have discovered ways to target the Leukaemic Stem Cell (LCSs). TKI therapies do not eradicate the disease in the majority of people as they do not switch off the abnormal stem cell that all CML cells develop from. In a small minority develop resistance to this class of drug. Teams on both sides of the Atlantic have been working hard to find ways to target Leukaemia Stem Cells.

ABL001 is a small molecule inhibitor of BCR-ABL, which is the same protein target of nilotinib and imatinib. Unlike the TKIs, ABL001 does not bind in the ATP domain; instead, it binds to a myristate site that causes a conformational change and switches off the kinase activity. “The advantage is that it doesn’t have effects on other kinases, unlike all of the TKIs, so it is better tolerated,” Hughes explained.

Stemming the regrowth of leukemia

Original Article

Leukemia (2016) 30, 

823–832; doi:10.1038/leu.2015.329;published online 19 January 2016

“Genetically, disease progression is associated with the acquisition of further chromosomal aberrations or mutations,” wrote study authors led by Mirle Schemionek, PhD, of University Hospital RWTH Aachen in Germany. “At the epigenetic level, DNA promoter methylation of specific genes, often tumor suppressors, has been associated with disease progression.”