Breast cancer drug could be used to treat life-threatening leukaemia

A recently-approved breast cancer drug could be used to target and treat a life-threatening leukaemia, new research has revealed.

Experts at the Universities of Birmingham and Newcastle have identified that the drug, palbociclib, used for advanced breast cancer, can work effectively on treating acute myeloid leukaemia (AML).

Unlike current chemotherapy used to fight AML, palbociclib has significantly less toxic side-effects, such as irreversible heart damage and hair loss.

The study, carried out on cell lines in the laboratory and on a mouse model, is published in Cancer Cell and is a key step towards targeted treatment for adults and children with the serious condition.

It is hoped that this research development could increase survival rates for patients in the future.

Professor Constanze Bonifer, of the University of Birmingham’s Institute of Cancer and Genomic Sciences, said: “Effective targeted therapies have yet to be developed for the majority of acute leukaemia subtypes.

“Treatments generally involve intensive and toxic chemotherapy, which can severely impair the quality of a patient’s life, both during treatment and in the longer term.

“The toxicity of current treatments, as well as the fact that long-term survival is less than 70 per cent even in acute myeloid leukemia subgroups with a good prognosis, shows that it is vital that we find new ways to treat this disease.

“This research is part of wider work being carried out by my team at the University of Birmingham which uses big data to discover innovative and ground-breaking ways to treat AML.”

Professor Olaf Heidenreich, from the Wolfson Childhood Cancer Research Centreat Newcastle University who used the Birmingham data to design a drug-target screen, said: “Last year, palbociclib was approved for use in patients and was hailed by many experts as the most important breakthrough for women with advanced breast cancer in years.

“Our discovery that this treatment can be effective in AML is an important step towards a more effective and less toxic treatment for patients with this form of leukaemia.

“In addition to a significant number of treatment failures, long-term side effects such as cardiotoxicity or treatment-associated cancers are the scourge of current chemotherapy for AML.

“This discovery will help advance treatment without severely impairing patients’ quality of life.”

Palbociclib, which is taken in tablet form, can stop the spread of breast cancer in terminally ill patients for up to two years.
The treatment has been designed to thwart tumour growth by preventing key molecules of cell cycle progression from doing their job.

Specifically, palbociclib inhibits cyclin-dependent kinase 4 (CDK4) and closely-related CDK6; two factors that are essential to drive cells into DNA replication phase, which leads to cancer.

Scientists at both universities performed genomic analysis on AML cells and identified that two key molecules involved in the progression of leukaemia are CDK6 and CCND2.

As a result, it was established that the disease can be therapeutically targeted by repurposing palbociclib as the drug drives malignant CDK6 cells into death.

Professor Heidenreich said: “We are now carrying out research to identify combinations of medicines containing palbociclib that will effectively eradicate AML without causing substantial therapy-associated ‘collateral damage’.”

Each year, there are approximately 2,500 AML deaths in the UK and around 3,100 new cases of the disease.

For more information please contact Emma McKinney, Communications Manager (Health Sciences), University of Birmingham, tel: +44 (0) 121 414 6681, or contact the press office on +44 (0) 7789 921 165.

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• Martinez-Soria et al. ‘The oncogenic transcription factor RUNX1/ETO corrupts cell cycle regulation to drive leukaemia transformation.’ Cancer Cell. DOI: 10.1016/j.ccell.2018.08.015
• As well as Professor Bonifer, the study involved the following academics from the University of Birmingham: Peter Cockerill, Sandeep Potluri, Anna Pickin, Paulynn Suyin Chin, Daniel Coleman, Salam Assi, Anetta Ptasinska and Dorothy Mueller. Their work was funded by Bloodwise, MRC and involves a collaboration between the two CRUK Centres in Newcastle and Birmingham.