Breast cancer is a heterogeneous disease, with a high degree of diversity between patients and within a given tumour. Although breast cancer can be stratified histologically and molecularly into different subtypes, the clonogenicity and invasive potential of various cellular subsets within the tumour remain to be determined. This should lead to a better understanding of disease progression and potentially lead to new therapies to prevent relapse of the disease.
Primary tumours are hierarchically organised entities, sustained by a highly tumorigenic population of cancerinitiating cells (Visvader and Lindeman, 2012). This project aims to determine the clonal diversity within breast tumours, and to understand how a single cell contributes to tumour progression and relapse by determining it’s expression profile.
One of the most comprehensive ways to address breast cancer heterogeneity is through the use of ‘cellular barcoding’ and single cell gene expression analyses (Fennell et al, 2021). Retroviruses can be used to introduce different barcodes into primary cells (Merino et al, 2019) in order to mark individual cells, either precancerous or tumour cells. These cells, and their progenitors, can then be tracked in vivo to investigate clonal evolution in the context of tumour behaviour. This study should provide key insights into cancer progression and relapse.
References
- Visvader, J.E., and Lindeman, G.J. (2012). Cancer stem cells: current status and evolving complexities. Cell Stem Cell 10, 717-728.
- Merino D, Weber TS, Serrano A, Vaillant F, Liu K, Pal B, Di Stefano L, Schreuder J, Lin D, Chen Y, Asselin-Labat ML, Schumacher TN, Cameron D, Smyth GK, Papenfuss AT, Lindeman GJ, Visvader JE*, Naik SH*. (2019) Barcoding reveals complex clonal behavior in patient-derived xenografts of metastatic triple negative breast cancer. Nat Commun. 10(1), 766.
- Fennell KA, Vassiliadis D, Lam EYN, Martelotto LG, Balic JJ, Hollizeck S, Weber TS, Semple T, Wang Q, Miles DC, MacPherson L, Chan YC, Guirguis AA, Kats LM, Wong ES, Dawson SJ, Naik SH, Dawson MA. (2022). Nongenetic determinants of malignant clonal fitness at single-cell resolution. Nature. 601, 125–131
