Biomarkers May Predict Chemo-Resistant Breast Cancers
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 found.
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.
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"Pilot and feasibility study: comparative proteomic analysis by 2-DE MALDI TOF/TOF MS reveals 14-3-3 proteins as
putative biomarkers of response to neoadjuvant chemotherapy in ER-positive breast cancer"; Victoria C. Hodgkinson,
Vijay Agarwal, Dalia ELFadl, John N. Fox, Penelope L. McManus, Tapan K. Mahapatra, Peter J. Kneeshaw, Philip J. Drew,
Michael J. Lind, Lynn Cawkwell; Journal of Proteomics, In Press, Uncorrected Proof, Available online 3 April 2012;
DOI: 10.1016/j.jprot.2012.03.049; Link to Abstract.
Addtitional sources: University of Hull.
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