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Dr Sacha Howell

Sacha Howell carries out trials of new breast cancer drugs. He is particularly interested in approaches to overcome resistance to hormone therapy.

Senior Clinical Lecturer

The University of Manchester
Wilmslow Road
M20 4BX


Dr Howell graduated from The University of Nottingham Medical School in 1993. After completion of basic medical training and year working overseas in Grenada he entered entered specialist training in Medical Oncology in 1999 at The Christie Hospital. He was awarded CCT in 2006, and in the same year was awarded his PhD from The University of Manchesterduring which he defined a previously unidentified role for prolactin signalling in breast cancer stem/progenitor cell regulation. Following a period as a senior clinical research fellow he was appointed as a Senior Lecturer at The University of Manchester in 2010. His professional time is divided between the clinical care of cancer patients at The Christie and both basic and clinical research at the CRUK Manchester Institute and The Christie respectively.

Patient-derived Mammosphere and Xenograft Tumour Initiation Correlates with Progression to Metastasis.

Eyre, R., Alférez, D. G., Spence, K., Kamal, M., Shaw, F. L., Simões, B. M., Santiago-Gómez, A., Sarmiento-Castro, A., Bramley, M., Absar, M., Saad, Z., Chatterjee, S., Kirwan, C., Gandhi, A., Armstrong, A. C., Wardley, A. M., O'Brien, C. S., Farnie, G., Howell, S. J. & Clarke, R. B.

Journal of Mammary Gland Biology and Neoplasia.  28 Sep 2016.

Low prevalence of HER2 positivity amongst BRCA1 and BRCA2 mutation carriers and in primary BRCA screens

Evans, G., Lalloo, F., Howell, S., Verhoef, S., Woodward, E. R. & Howell, A. 18 Feb 2016

Breast Cancer Research and Treatment. 2016. 155(3):597-601

A phase II trial of low-dose estradiol in postmenopausal women with advanced breast cancer and acquired resistance to aromatase inhibition

Zucchini, G., Armstrong, A. C., Palmieri, C., Howell, S. J., Wardley, A. M., Wilson, G., Misra, V., Seif, M., Ryder, W. D., Cope, J., Blowers, E. & Howell, A.

European Journal of Cancer. 2015. 51(18):2725-31

Anti-estrogen Resistance in Human Breast Tumors Is Driven by JAG1-NOTCH4-Dependent Cancer Stem Cell Activity.

Simões, B. M., O'Brien, C. S., Eyre, R., Silva, A., Yu, L., Sarmiento-Castro, A., Alférez, D. G., Spence, K., Santiago-Gómez, A., Chemi, F., Acar, A., Gandhi, A., Howell, A., Brennan, K., Rydén, L., Catalano, S., Andó, S., Gee, J., Ucar, A., Sims, A. H., Marangoni, E., Farnie, G., Landberg, G., Howell, S. J., Clarke, R. B.

Cell Reports. 2015. 12, 12, p. 1968-1977 9 p.

The role of steroid hormones in breast cancer stem cells

Simões, B. M., Alferez, D., Howell, S. & Clarke, R. 17 Sep 2015

Endocrine-related cancer.  2015. 22(6):T177-86

Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer.

Palmieri, C., Macpherson, I. R., Yan, K., Ades, F., Riddle, P., Ahmed, R., Owadally, W., Stanley, B., Shah, D., Gojis, O., Januszewski, A., Lewanski, C., Asher, R., Lythgoe, D., de Azambuja, E., Beresford, M. & Howell, S. J.

Oncotarget. 2015. 15;7(11):13209-20.

Doxycycline down-regulates DNA-PK and radiosensitizes tumor initiating cells: Implications for more effective radiation therapy.

Lamb, R., Fiorillo, M., Chadwick, A., Ozsvari, B., Reeves, K. J., Smith, D., Clarke, R., Howell, S. J., Cappello, A. R., Martinez-Outschoorn, U. E., Peiris Pages, M., Sotgia, F. & Lisanti, M.

Oncotarget. 2015. 6(16):14005-25.

Breast cancer: current and future endocrine therapies.

Palmieri C, Patten DK, Januszewski A, Zucchini G, Howell SJ.

Mol Cell Endocrinol. 2014 Jan 25;382(1):695-723. doi: 10.1016/j.mce.2013.08.001.

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer.

Eccles SA et al.

Breast Cancer Res. 2013 Oct 1;15(5):R92. doi: 10.1186/bcr3493.

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.

Clin Cancer Res. 2013 Feb 1;19(3):643-56. doi: 10.1158/1078-0432.CCR-12-1063.

HER2-targeted therapy in breast cancer: a systematic review of neoadjuvant trials.

Dent S, Oyan B, Honig A, Mano M, Howell S.

Cancer Treat Rev. 2013 Oct;39(6):622-31. doi: 10.1016/j.ctrv.2013.01.002.

The clinical effectiveness and cost-effectiveness of genotyping for CYP2D6 for the management of women with breast cancer treated with tamoxifen: a systematic review.

Fleeman N, Martin Saborido C, Payne K, Boland A, Dickson R, Dundar Y, Fernández Santander A, Howell S, Newman W, Oyee J, Walley T.

Health Technol Assess. 2011 Sep;15(33):1-102. doi: 10.3310/hta15330.

Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer.

Board RE, Wardley AM, Dixon JM, Armstrong AC, Howell S, Renshaw L, Donald E, Greystoke A, Ranson M, Hughes A, Dive C.

Breast Cancer Res Treat. 2010 Apr;120(2):461-7. doi: 10.1007/s10549-010-0747-9.

Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor.

Harrison H, Farnie G, Howell SJ, Rock RE, Stylianou S, Brennan KR, Bundred NJ, Clarke RB.

Cancer Res. 2010 Jan 15;70(2):709-18. doi: 10.1158/0008-5472.CAN-09-1681.

Dr Howell’s major research interest is in translational breast oncology, with a focus on endocrine therapy resistance. He holds grants to test novel antagonists of both oestrogen and progesterone receptor signalling in preclinical models in collaboration with Dr Robert Clarke in the Breast Biology Groupin addition to translating these studies into multicentre investigator led clinical trials. These include a 25 centre multinational randomised phase II study testing the AKT inhibitor AZD5363 in combination with the oestrogen receptor down regulator fulvestrant which is actively recruiting.

Most recently Dr Howell was awarded a Breast Cancer Campaign project grant to run a pilot study repurposing the antiprogestin ulipristal acetate from the treatment of uterine fibroids to the prevention of breast cancer. This study will harness expertise across the Manchester Breast Centre, defining the roles of progesterone signalling in epithelial, stromal and stem cell compartments with imaging correlates of response to identify women at increased risk of breast cancer who may benefit from this preventative therapy.

SJ Howell, C Searle, V Goode, T Gardener, RA Cowan, MA Harris, P Hopwood, K Linton, R Swindell, J Kennedy, P Chatterjee, A Norman, A Howell, JA Radford. The UK National Breast Cancer (BC) Screening Programme for Hodgkin Lymphoma (HL) Survivors Detects BC at an Early Stage. British Journal of Cancer 2009; 18: 582-8.

Howell SJ, Wardley AM, Armstrong AC. Re: Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009; 101:1730

Resistance to endocrine therapy: are breast cancer stem cells the culprits?

CS O'Brien, SJ Howell, G Farnie, RB Clarke - Journal of mammary gland …, 2009 - Springer

Impaired tamoxifen metabolism reduces survival in familial breast cancer patients

…, A Shenton, C McHague, F Lalloo, S Howell… - Clinical Cancer …, 2008 - AACR

Origins of breast cancer subtypes and therapeutic implications

AH Sims, A Howell, SJ Howell, RB Clarke - Nature Clinical Practice …, 2007 -

The use of selective estrogen receptor modulators and selective estrogen receptor down-regulators in breast cancer

SJ Howell, SRD Johnston, A Howell - Best Practice & Research Clinical …, 2004 - Elsevier