Polymer delivers double whammy to breast cancer
a new method of delivering drugs for treating breast cancer that
promises to be more effective than current treatments
Despite the emergence of new, more selective drugs, the high incidence of breast cancer (1 in 8 women) and the low survival in the metastatic disease (less than 20 per cent) show that current therapy is not fully effective.
Polymer-drug conjugation has been shown to decrease drug toxicity, increase tumour targeting by the enhanced permeability and retention (EPR) effect - the polymer accumulates in tumour tissue which should decrease side effects by reducing exposure of non-tumour tissues to the drug - and has the ability to bypass some resistance mechanisms.
For the first time, the Cardiff researchers have shown that it is possible to combine both cytotoxic and hormonal treatments for breast cancer into a single polymer chain.
They used N-(2-hydroxypropyl)-methacrylamide (HPMA) copolymer, as this has already been used to deliver the first-line breast cancer drug doxorubicin with promising results in Phase I/II clinical trials. The anticancer agent is linked (conjugated) to the polymer using a biodegradable linker that is broken down by enzymes inside the tumour cell, releasing the active drug.
The group, headed by Francesco Greco of the Centre for Polymer Therapeutics at Cardiff, chose to combine doxorubicin and the aromataseinhibitor aminoglutethimide with HPMA in the in vitro study using breast cancer cell lines.
The HPMA copolymer-AGM-Dox combination therapy showed marked superiority in vitro compared with individual polymer conjugates carrying doxorubicin or AGM alone.
The team said it now plans to carry out further studies to understand better the intracellular mechanisms behind this improved activity, and to assess whether these conjugates potential to inhibit tumour growth in vivo.
