Manchester University (UK) scientists have a developed a new method to monitor the
effect of anti-cancer drugs on very rare leukaemia stem cells. The
approach potentially allows doctors to screen patients and personalise
their treatment.
The recent development of novel agents has improved outcomes for
patients with chronic myeloid leukaemia (CML). These so-called tyrosine
kinase inhibitors (TKIs) target abnormal proteins caused by commonly
found genetic mutations in CML patients. However, the existence of
treatment-resistant cancer stem cells – cells that are able to
repeatedly renew the leukaemia cell population – is one way that many
patients experience disease recurrence when treatment stops.
Any
new drug must therefore be tested on such stem cells, but unfortunately
they are only found in very low numbers and are identified by certain
cell surface markers. Now researchers at The University of Manchester –
part of the Manchester Cancer Research Centre – have tested a way to monitor the effect of drugs on small samples of cells.
Professor Tony Whetton,
head of the Stem Cell and Leukaemia Proteomics Laboratory who led the
study, said: “Current techniques require greater numbers of cells in
order to detect changes caused by TKIs. Our study investigated the
potential of a new technology platform that can identify changes in very
small cell numbers.”
The research team looked at an
antibody-based approach to detect structural changes in certain
proteins, in order to track the effectiveness of the TKI drugs. The
instrument used fixes proteins in place and holds them, there allowing
for a better signal to be generated from less material. With this
approach they found that they could record changes in samples of only a
few thousand critically important but rare stem cells.
“This new
approach will enable us to test drugs on cells taken from patients,
either at presentation or in a clinical trial setting. It has great
potential to allow us to implement precision medicine, where patients
receive the most appropriate treatment to target their individual
tumour,” added Professor Whetton.