PhD in Molecular Oncology
Job No:
G123
Location:
Darlinghurst, Sydney
Project title: New therapeutic strategies for triple negative breast cancer
Supervisors: Dr Alex Swarbrick and A/Prof Elgene Lim
The prognosis for breast cancer patients has improved markedly in the last 30 years, driven mainly by the development of drugs targeting the Estrogen (ER) and Her2 receptors. However, patients with so-called ‘Triple negative’ breast cancer (TNBC), have not benefitted from these discoveries as their tumours do not express the Estrogen or Her2 receptors. TNBC accounts for ~ 15% of diagnoses, occurs in younger patients than other subtypes and has a poor prognosis, with up to 40% of women dying within 5 years of diagnosis. For these patients conventional chemotherapy remains the only drug option. We need to do better.
We are using our unique insights into the biology of TNBC to develop new drug options for this aggressive disease. We have 3 areas of interest in which we are investigating TNBC biology and conducting preclinical studies:
1) Tumour stroma. Cancers are complex ecosystems in which many non-neoplastic cells play important roles. We have shown a critical role for cancer-associated fibroblasts (CAFs) in providing a ‘niche’ for cancer cells to reside in a stem-like drug-resistant state.
2)Endocrine therapy. While TNBC do not express ER, many express the related Androgen receptor (AR). There is evidence that AR may drive tumour growth in certain TNBC.
3) Immunotherapy. New agents that activate the immune system are showing remarkable success in the treatment of certain cancers. The results in breast cancer are less dramatic, however clinical benefit has been seen in a proportion of TNBC patients. We aim to uncover how breast cancers resist immunotherapy and devise new strategies to sensitise TNBC to immunotherapy.
To provide a world class preclinical experimental platform, we have developed a large collection of patient-derived xenograft (PDX) models of disease. Here fresh breast cancer tissue is grown in immunodeficient mice. PDX maintain many of the features of their parent cancer and are the gold standard for preclinical studies. PDX moldes are complemented by a series of syngenic models in which mice maintain intact immune systems.
We are looking for an enthusiastic applicant to join our multidisciplinary team of biologists, oncologists, pathologists and bioinformaticians.
This project would suit someone with an interest and background in Medical Oncology, Cancer cell biology or related disciplines.