Researchers at the University of Hull in the UK have identified a family of proteins that could potentially be used as
biomarkers to predict resistance to chemotherapy in estrogen receptor-positive (ER-positive) breast cancer patients.
In an "in press" issue of their study published online in the Journal of Proteomics on 3 April, lead researcher Dr Lynn
Cawkwell and colleagues explain how they discovered a number of potential biomarkers for resistance to epirubicin, docetaxel
and other chemo drugs.
Resistance to chemotherapy is a big problem in the treatment of some types of cancer.
Without a means to predict whether chemo will work, some patients with resistant cancers undergo much hardship: suffering the
side effects of ineffective chemo options without the benefits, plus they lose valuable time until an effective therapy is
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So a major goal in cancer research is to predict how particular cancers might respond, and one way to do this is to test for
particular proteins or biomarkers.
"Unfortunately, a reliable test has not yet been developed to achieve
this [for ER-positive breast cancer]. We hope our work can
help to bring us a step closer," Cawkwell told the press.
Some scientists working in this field use cell lines to try and track down biomarkers, but Cawkwell's team used clinical breast
tumour tissue samples taken from patients, which she says helped them gain a "more accurate representation of what is relevant
in real-life diseases".
For their study, Cawkwell and colleagues also used two "high-throughput processes", one based on antibodies and the other using
mass spectrometry, to identify candidate biomarker proteins.
Using these to conduct "comparative proteomic experiments", they
identified 132 unique proteins that were significantly
differently expressed (more than two-fold) in chemo-resistant samples,
57 of which were identified in at least two experiments,
they write.
Five of the proteins in the 57 candidates belong to the 14-3-3 protein family (namely the "isoforms" theta/tau, gamma, epsilon,
beta/alpha and zeta/delta), and have previously been associated with chemotherapy resistance in breast cancer.
The team says their findings confirm the 14-3-3 protein family as a
strong candidate for a predictive test for chemo-resistance.
The team is now working on showing how these proteins might be used as biomarkers to predict chemo-resistant ER-positive breast
cancers. Cawkwell said:
"If we're correct, we hope that by testing for these proteins, doctors
will be able to anticipate a patient's response to different
chemotherapies, and decide which course of treatment is most appropriate
for them."
The team is also investigating radiotherapy resistance in a number of different cancers.