Chronic lymphocytic leukemia (CLL) is the most common form of
leukemia, with over 4,000 cases in the United Kingdom every year. At the moment CLL
is incurable, but in recent years, new drugs called B-cell receptor
(BCR) inhibitors, have revolutionized treatment.
However, it is not entirely clear how they work and why they are so
effective. In addition, some patients can become resistant to these
types of drugs.
‘The B-cell receptor (BCR) inhibitor idelalisib disrupts important survival signals from within the tumor and prevents communication from surrounding cells that help the tumor survive; causing the tumor cells to die.’
Researchers at the University of Southampton have shed new light on
why and how this new class of drug is effective at fighting off leukemia.
The study, led by Professor Mark Cragg at the University of
Southampton and funded by The Kay Kendall Leukemia Fund and Bloodwise,
has characterized the molecular mechanisms responsible for how one of
these drugs (idelalisib) work.
Published in the journal Leukemia
, the study treated blood
cells from CLL patients in the laboratory with idelalisib and found it
disrupts important survival signals from within the tumor and prevents
communication from surrounding cells that help the tumor survive;
causing the tumor cells to die.
The response to idelalisib was linked to an increased production of a
protein called Bim, which is responsible for the tumor cell death.
Their results also showed idelalisib-like drugs can be successfully
combined with antibody treatments to more effectively eradicate the
cancer and give longer lasting protection and that this combination
effect is also dependent on Bim.
Professor Cragg said, "These results are very interesting and
positive. We now know how the drug is able to attack and slow the growth
of the tumors, but not get rid of it completely. We also know that Bim
is required for the death and for the combination effects with antibody
treatments. With this knowledge we can design better, more effective
combination treatments. In the future, we could even be looking at
combinations that will give us a cure for some blood cancers where we
don't currently have that possibility."
Dr. Alasdair Rankin, Director of Research at Bloodwise, said,
"Idelalisib and other BCR inhibitors have transformed the outlook for
patients with CLL, but we are still not entirely clear how they work and
why they are so effective. We now have a rising number of treatments
available to people with CLL. A deeper understanding of how these drugs
work is needed to guide treatment decisions and identify combinations
that deliver the best benefits for patients."