ADAM22 as a predictive marker for endocrine resistant metastatic breast cancer and an LGI1 mimetic as a companion therapeutic
Approximately 70 % of breast cancer patients are classified as oestrogen receptor positive. While initial prognosis is favourable, the risk of recurrence remains long after diagnosis. Furthermore, the ability to treat recurrent tumours becomes harder over time as resistance to endocrine therapy develops. This resistant phenotype is caused in part by overexpression of the nuclear receptor co-activator SRC-1. Moreover, SRC-1 has been shown to promote metastatic development in several breast cancer models.
Previously, our lab identified the neuronal protein ADAM22 as an SRC-1 target gene involved in endocrine resistant breast cancer metastases. Here, this metastatic role was further characterised through knockdown, knockout and overexpression studies along with a high throughput proteomic study. This study demonstrates the potential of ADAM22 as a biomarker for predicting metastatic development in endocrine resistant patients. Finally, an ADAM22 targeting peptide mimetic was shown here to reverse ADAM22 mediated metastatic characteristics both in vitro and in vivo.
Irish Cancer Society (Breast Predict)
First SupervisorProfessor Leonie Young
Second SupervisorProfessor Arnold Hill
CommentsA thesis submitted for the degree of Doctor of Philosophy from the Royal College of Surgeons in Ireland in 2018.
Published CitationDoherty B. ADAM22 as a predictive marker for endocrine resistant metastatic breast cancer and an LGI1 mimetic as a companion therapeutic [PhD Thesis]. Dublin: Royal College of Surgeons in Ireland; 2018.
- Doctor of Philosophy (PhD)