Dr Nicole Haynes, Prof Ricky Johnstone, A/Prof Sherene Loi
Sir Peter MacCallum Department of Oncology, The University of Melbourne
The introduction of trastuzumab (Herceptin)- based chemotherapy combinations into clinical practice has revoluntionized the treatment of human epidermal growth factor receptor 2-positive (HER2+) breast cancer.
However, less than 35% of patients with HER2+ breast cancer demonstrate an initial response to anti-HER2-based combination therapy. Of those patients with metastatic disease who initially respond to treatment, 70% will relapse within a year of treatment initiation.
This study will examine the unique ability of the anti-cancer drug panobinostat to promote and/or complement the therapeutic actions of trastuzumab in models of HER2+ breast cancer.
What is the need?
Within Australasia HER2+ breast cancer accounts for 12-15% of all breast malignancies. While targeted treatments do exist, the diverse nature of this disease, high incidence of resistance and lack of reliable biomarkers to identify patients likely to benefit, has meant that many women are over-treated with toxic and expensive therapies.
Already, our finding have highlighted the immune enhancing effects of panobinostat and its potent ability to augment the anti-cancer actions of trastuzumab in models of HER2+ breast cancer. Most striking, and possibly clinically important, has been the capacity of the combination therapy to eradicate established trastuzumab-refractory HER2+ breast tumours - a key area of unmet medical need.
What impact will this research have?
Findings from this study will ensure the full therapeutic potential of trastuzumab and panobinostat can be effectively harnessed against HER2+ breast cancer; particularly in patients whoes cancer has become resistant to trastuzumab therapy.
Better understanding how the body's immune defences can be harnessed to promote the effectiveness of trastuzumab will help identify new strategies to amplify the therapeutic impact of the combination therapy.
Characterisation of mechanisms that can eradicate anti-HER2 sensitive and resistant HER2+ tumours.
Demonstrate the therapeutic efficacy of panobinostat and trastuzumab.
Establish how tumour-immune contexture can influence the therapeutic activity of anti-HER2- targeted therapies.
| Demonstrate how panobinonstat can augment the ability of trastuzumab to eradicate cancer stem cells and reduce disease reccurrence.
"Already our findings have highlighted the immune enhancing effects of panobinostat and its potent ability to augment the anti-cancer actions of trastuzumab in models of HER2+ breast cancer."