Gillian Farnie investigates Cancer Stem Cells (CSCs) in invasive and pre-invasive breast cancer.

Breast Cancer Now Fellow

Institute of Cancer Sciences
Paterson Building
The University of Manchester
Wilmslow Road
Withington
Manchester
M20 4BX

Email: gillian.farnie@manchester.ac.uk
Tel: +44 (0)161 446 3230

1999, BSc(Hons) Pharmacology, University Of Liverpool

2002, Ph.D Molecular Oncology, University Of Newcastle Upon Tyne

2002-2008, Postdoctoral Research Associate, School of Cancer Studies, University Of Manchester

2008-Present, Breast Cancer Campaign Fellow, School of Cancer Studies, University Of Manchester

My PhD was undertaken at the Northern Institute for Cancer Research, University of Newcastle Upon Tyne. Here I investigated the MDM2 oncogene as a therapeutic target for cancer.

My first post-doctoral appointment was within the School of Cancer Studies at the University of Manchester in the laboratory of Dr Neil Anderson and Professor Nigel Bundred. Here I developed a novel culture system to grow human ductal carcinoma in situ (DCIS), and further investigate the role of epidermal growth factor receptor family. During this research I discovered DCIS tissue contained cancer stem cells that could initiate mammospheres and Notch signalling played an important role in DCIS. This led to a successful Breast Cancer Campaign grant application in 2005 as a co-applicant with Professor Nigel Bundred to continue my research into the role of Notch in DCIS CSC regulation.

I lead my own research group since the award of a Breast Cancer Campaign fellowship in 2008. The main focus of this research is to investigate the role of breast cancer stem cells in the resistance to radio and chemotherapy.

A differential role for CXCR4 in the regulation of normal versus malignant breast stem cell activity.

Matthew P. Ablett, Ciara S. O’Brien, Andrew H. Sims, Gillian Farnie and Robert B. Clarke. (2014).

Oncotarget, 5(3), 599-612.

Focal Adhesion Kinase and Wnt signalling regulates human Ductal Carcinoma in situ stem cell activity and response to radiotherapy. 

Williams K, Bundred NJ Landberg G, Clarke RB, Farnie G. (2014).

Stem Cells

Combined Inhibition of ErbB1/2 and Notch Receptors Effectively Targets Breast Ductal Carcinoma In Situ (DCIS) Stem/Progenitor Cell Activity Regardless of ErbB2 Status.

Farnie G, Willan PM, Clarke RB, Bundred NJ. (2013).

PLoS One, 8(2), e56840. 

Lapatinib inhibits stem/progenitor proliferation in preclinical in vitro models of ductal carcinoma in situ (DCIS).

Gillian Farnie, Rachael L Johnson, Kathryn E Williams, Robert B Clarke and Nigel J Bundred. (2013).

Cell Cycle, 13(3), 418-425.

Targeting CXCR1/2 significantly reduces breast cancer stem cell activity and increases the efficacy of inhibiting HER2 via HER2-dependent and -independent mechanisms. 

Singh JK, Farnie G, Bundred NJ, Simões BM, Shergill A, Landberg G, Howell SJ, Clarke RB. (2013).

Clinical Cancer Research, 19(3), 643-656.

A detailed mammosphere assay protocol for the quantification of breast stem cell activity. 

Shaw FL, Harrison H, Spence K, Ablett MP, Simoes BM, Farnie G, Clarke RB. (2012).

Journal of Mammary Gland Biology and Neoplasia, 17(2), 111-117.

P-cadherin is coexpressed with CD44 and CD49f and mediates stem cell properties in basal-like breast cancer.

Vieira AF, Ricardo S, Ablett MP, Dionísio MR, Mendes N, Albergaria A, Farnie G, Gerhard R, Cameselle-Teijeiro JF, Seruca R, Schmitt F, Clarke RB, Paredes J. (2012).

Stem Cells, 30(5), 854-864.

Resistance to Endocrine Therapy in Breast Cancer: Are Breast Cancer Stem Cells Implicated?.

Ciara S. O’Brien, Sacha J. Howell, Gillian Farnie and Robert B. Clarke. (2011).

Stem Cell Biology and Regenerative Medicine. (pp. 381-402).

Application of Stem Cell Assays for the Characterization of Cancer Stem Cells.

Willan PM. and Farnie G. (2011).

Stem Cell Biology and Regenerative Medicine. (pp. 259-282).

Breast Cancer Stem Cells and Their Role in Resistance to Endocrine Therapy. 

Ciara S. O’Brien, Gillian Farnie, Sacha J. Howell and Robert B. Clarke. (2011).

Hormones and Cancer, 2(2), 91-103.

The main focus of our research is to investigate Cancer Stem Cells (CSCs) in invasive and pre-invasive breast cancer.

A tumour can be defined as an aberrantly differentiated tissue containing its own cancer stem cells (CSCs), the tumour or cancer-initiating cells. The CSC hypothesis proposes that heterogeneous tumours are hierarchical and derived from CSCs, which are inherently resistant to current therapeutic approaches such as radio and chemotherapy due to their ability to repair DNA, efflux toxins and survive hypoxic conditions. After radio or chemotherapy the main bulk of tumour cells are killed but the CSCs survive and are able to reinitiate a new tumour at a later date.

We are investigating why CSCs can avoid or survive radio and chemotherapy. This will identify new targets can then be used to eliminate CSC and/or sensitise CSCs to these treatments.

Methodologies

My laboratory has specialised expertise in:

Extracting, isolating and culturing primary breast cancer samples in vitro and in vivo

Cancer stem cell (CSC) assays

·       Sphere culture, including self-renewal through secondary generation sphere formation

·       Flow cytometry for CSC cell surface markers (ESA⁺/CD44⁺/CD24^low/- and Aldefluor).

·       in vivo limiting dilution assay

DCIS culture models

·       3D matrigel, hydrogel models

·       in vivo xenografts

Current and Future projects

-       Investigating Histone deacetylase (HDAC) inhibitors to determine if inducing differentiation in CSCs prevents their capacity to resist DNA-damage.

-       Focal Adhesion Kinase /Wnt signalling cross talk and its regulation of self-renewal and radio/chemotherapy resistance (collaboration with Nigel Bundred)

-       The role of metabolism in cancer stem cells (collaboration with Michael Lisanti and Federica Sotgia)

-       The development of a hydrogels to improve in vitro model of DCIS (collaboration with Cathy Merry)

Harrison H, Farnie G, Howell SJ, Rock RE, Stylianou S, Brennan KR, Bundred NJ, Clarke RB. (2010). Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor. Cancer Research, 70(2), 709-718. eScholarID:76715 | DOI:10.1158/0008-5472.CAN-09-1681

O'Brien CS, Howell SJ, Farnie G, Clarke RB. (2009). Resistance to endocrine therapy: are breast cancer stem cells the culprits? J Mammary Gland Biol Neoplasia, 14(1), 45-54. eScholarID:76717 | DOI:10.1007/s10911-009-9115-y

O'Brien C, Farnie G, Howell S, Clarke R. (2008). Are stem-like cells responsible for resistance to therapy in breast cancer? Breast Dis, 29, 83-89. eScholarID:1d32619

Barnes N, Warnberg F, Farnie G, White D, Jiang W, Anderson E, Bundred N. (2007). Cyclooxygenase-2 inhibition: effects on tumour growth, cell cycling and lymphangiogenesis in a xenograft model of breast cancer. Br J Cancer, 96( 4), 575-82. eScholarID:1d32497 | DOI:10.1038/sj.bjc.6603593

Farnie G, Clarke RB, Spence K, Pinnock N, Brennan K, Anderson N, Bundred NJ. (2007). Novel cell culture technique for primary ductal carcinoma in situ: role of Notch and epidermal growth factor receptor signaling pathways. J Natl Cancer Inst, 99(8), 616-627. eScholarID:1d15720 | DOI:10.1093/jnci/djk133

Farnie G, Clarke RB. (2007). Mammary stem cells and breast cancer--role of Notch signalling. Stem Cell Rev, 3( 2), 169-75. eScholarID:1d32606

Farnie G, Clarke R. (2006). Breast stem cells and cancer. Ernst Schering Found Symp Proc, ( 5), 141-53. eScholarID:1d32607 | DOI:10.1016/j.bbcan.2012.01.002

Hardcastle, I, Ahmed, S, Atkins, H, Farnie, G, Golding, B, Griffin, R, Guyenne, S, Hutton, C, Källblad, P, Kemp, S, Kitching, M, Newell, D, Norbedo, S, Northen, J, Reid, R, Saravanan, K, Willems, H, Lunec, J. (2006). Small-molecule inhibitors of the MDM2-p53 protein-protein interaction based on an isoindolinone scaffold. J Med Chem, 49( 21), 6209-21. eScholarID:1d31916 | DOI:10.1021/jm0601194

Hardcastle, I, Ahmed, S, Atkins, H, Calvert, A, Curtin, N, Farnie, G, Golding, B, Griffin, R, Guyenne, S, Hutton, C, Källblad, P, Kemp, S, Kitching, M, Newell, D, Norbedo, S, Northen, J, Reid, R, Saravanan, K, Willems, H, Lunec, J. (2005). Isoindolinone-based inhibitors of the MDM2-p53 protein-protein interaction. Bioorg Med Chem Lett, 15( 5), 1515-20. eScholarID:1d32393 | DOI:10.1016/j.bmcl.2004.12.061

Ahmad T, Farnie G, Bundred NJ, Anderson N. (2004). The mitogenic action of insulin-like growth factor I in normal human mammary epithelial cells requires the epidermal growth factor receptor tyrosine kinase. J Biol Chem, 279( 3), 1713-9. eScholarID:1d29479