Breast cancer poses a major global health problem as it is the most common type of cancer to affect women. Targeted treatments have resulted in a significant decrease in mortality rates in Hormone receptor and Her2 positive subtypes of breast cancer. Unfortunately, no targeted treatment exists for patients with the aggressive triple-negative breast cancer (TNBC) subtype. An in depth understanding of this disease is urgently required in order to enable improved therapies for TNBC that mainly affects young women and represents 10-20% of all breast cancer cases.
Research by our group has shown that the Inhibitor of Differentiation 1 (Id1) protein is expressed in TNBC within the subpopulation of tumour cells termed Cancer Stem Cells (CSCs) that drive malignancy. We have demonstrated that depletion of Id1 in a TNBC metastatic model resulted in reduced self-renewal capacity in vitro, delayed primary tumour growth, and significantly impaired lung metastasis formation in vivo. This indicates a pivotal role of Id1 in the CSC phenotype in TNBC.
To characterise the network of genes regulated by Id1, bioinformatics analyses were performed on array or RNA-Seq data from two different TNBC models of tumour cells marked by either Id1 depletion or expression and identified 34 high confidence targets of Id1. The requirement of these candidate genes for the viability, proliferation, and self-renewal of CSCs is currently being tested in vitro by knockdown studies using mainly the tumorsphere and proliferation assays. To further validate the best candidate genes in vivo, tumour growth as well as metastatic burden of knockdown TNBC cells transplanted into in mice will be assessed by in vivo imaging. Id1 targets that are important for the CSC phenotype and in vivo tumour formation are potential therapeutic targets with the future prospect of developing targeted treatment for TNBC patients.