Uncovering new mechanisms responsible for anti-estrogen therapy resistance

Start Year: 2012
Finish Year: 2015
Chief Investigator: Dr David Gallego-Ortega
Grant Type: Postdoctoral Fellowship
Institution: Garvan Institute of Medical Research

Postdoctoral Training Fellowship

The luminal subtype is the most common type of breast cancer, representing 50% of all breast cancer patients. The current first-line treatment for this cancer is the anti-oestrogen therapy with compounds such as tamoxifen. Unfortunately, most of the patients receiving this treatment relapse after developing endocrine resistance. These patients have a higher risk of developing metastasis (cancer spread).

Studies have identified the transcription factor Elf5 as a novel key determinant in endocrine resistance. Blocking the expression of Elf5 reduces dramatically the proliferation of endocrine-resistant tumour cells. Elf5 also specifies the more aggressive and lethal basal subtype, for which there is not available any targeted treatment.

Dr Gallego-Ortega will further study what molecules are under Elf5 regulation to understand the mechanism of endocrine acquired resistance. This understanding will provide new molecular targets that could be used to potentiate the current therapy.

He also will explore the relation of Elf5 with invasion and metastasis and hopes to create useful and comprehensive pre-clinical models.

This research will help determine how modulation of Elf5 expression can alter the acquisition of endocrine resistance and the lethal phenotype. Understanding the transcriptional network, driven by Elf5, could lead to new strategies and targeting candidates for future therapies.

This research is co-funded by NBCF and Cure Cancer Australia Foundation.