How can we combine cancer drugs to overcome resistance? PhD
student Sanne Huijberts and colleagues achieved promising results
for bowel cancer patients for a start. On October 14th
she will defend her thesis on research into various combination
Due to abnormalities in the DNA of cancer cells (mutations),
specific proteins can become hyperactive, leading to cancer growth.
By inhibiting these proteins with targeted drugs, this growth might
be prevented. Many of these drugs have been developed in recent
years, but the results are disappointing sometimes. The cancer cell
can switch to an alternative survival signal, preventing the
targeted therapy from being effective. This is called resistance,
which may already be present when the treatment starts or may be
developed during treatment.
Combining multiple drugs simultaneously or intermittently might
enhance their anticancer effect. Inhibiting the proteins that cause
resistance as well, for example, might improve the effectiveness of
the treatment. The drug combinations Sanne Huijberts' describes in
her thesis focus on overcoming resistance and, in specific, target
abnormal BRAF or KRAS proteins. Patients with such proteins often
face a poor prognosis and respond poorly to current therapies.
Huijberts describes promising results achieved in studies among
colon cancer patients with an abnormal BRAF protein. In these
patients, concomitant treatment with the BRAF inhibitor encorafenib
and the EGFR inhibitor cetuximab with or without the MEK inhibitor
binimetinib was shown to be safe and effective (
read more here). Recently, this combination was approved for
this patient group in the US and Europe.
Practical information about the defense can be found on
Utrecht University's website.
Thesis title: Translational research of combined anticancer
therapies targeting the MAPK pathway.