Research in our laboratory focuses on molecular aspects of cancer with particular emphasis on understanding the genotypic and phenotypic determinants of resistance to endocrine therapy in breast cancer.
Breast cancer is the most common malignancy in women, accounting for more than 400,000 deaths per year worldwide. Over three quarters of women diagnosed with breast cancer receive anti-oestrogen therapy. We aim to investigate the role of three newly identified genes in breast cancer. We have found that these genes are turned on in breast cancer at the same time as the oestrogen receptor. They also appear to be involved in the way breast cancers respond to treatment and may contribute to genetic susceptibility to breast cancer. We aim to determine why these genes are turned on together and how they then influence the rate at which cancer cells grow. We will also investigate how these genes influence a woman's risk of breast cancer and the way in which she will respond to treatment. Understanding the role of these genes will help to ensure patients receive the most appropriate treatment and to develop more effective therapies
The majority of breast cancers require the hormone oestrogen to grow. Drugs that act by preventing the production of oestrogen are the most effective treatment currently available for this type of cancer. However, these drugs do not work well for all patients. Our previous research suggests that attracting immune cells to the cancer site may cause the cancer to keep growing during therapy. This project aims to identify which immune cells are recruited to breast cancer cells during treatment and how the cancer cells signal to recruit them to the tumour. This research will help us to identify how breast cancers can evade therapy and to identify potential new drugs which could be used in combination with hormonal therapy to improve breast cancer treatments in the future.
Enquires about projects from prospective graduate students and postdoctoral fellows are welcome.
Suitably qualified students, from all countries, are eligible to apply for a University of Otago PhD scholarship (continually assessed) which covers tuition fees and provides a generous emolument for living expenses. If you are interested in this possibility please also make contact with me early on.
Elena Lopez-Knowles, Paul M Wilkerson, Ricardo Ribas, Helen Anderson, Alan Mackay, Zara Ghazoui, Aradhana Rani, Peter Osin, Ash Nerurkar, Lorna Renshaw, Alexey Larionov, William R Miller, J Michael Dixon, Jorge S Reis-Filho, Anita K Dunbier, Lesley-Ann Martin, and Mitch Dowsett., Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer., Breast Cancer Res 2015 vol. 17 (1) p. 35., Link »
Neill Patani, Anita K Dunbier, Helen Anderson, Zara Ghazoui, Ricardo Ribas, Elizabeth Anderson, Qiong Gao, Roger A'hern, Alan Mackay, Justin Lindemann, Robert Wellings, Jill Walker, Irene Kuter, Lesley-Ann Martin, and Mitch Dowsett, DIFFERENCES IN THE TRANSCRIPTIONAL RESPONSE TO FULVESTRANT AND OESTROGEN DEPRIVATION IN ER-POSITIVE BREAST CANCER., Clinical cancer research : an official journal of the American Association for Cancer Research 2014, Link »
Qiong Gao, Neill Patani, Anita K Dunbier, Zara Ghazoui, Marketa Zvelebil, Lesley-Ann Martin, and Mitch Dowsett, Effect of Aromatase Inhibition on Functional Gene Modules in Estrogen Receptor-Positive Breast Cancer and Their Relationship with Antiproliferative Response., Clinical cancer research : an official journal of the American Association for Cancer Research 2014, Link »
D C Sgroi, I Sestak, J Cuzick, Y Zhang, C A Schnabel, B Schroeder, M G Erlander, A Dunbier, K Sidhu, E Lopez-Knowles, P E Goss, and M Dowsett, Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: A prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population, The Lancet Oncology 2013 vol. 14 (11) pp. 1067-1076, Link »
Mitch Dowsett, Ivana Sestak, Elena Lopez-Knowles, Kalvinder Sidhu, Anita K Dunbier, J Wayne Cowens, Sean Ferree, James Storhoff, Carl Schaper, and Jack Cuzick, Comparison of PAM50 Risk of Recurrence Score With Oncotype DX and IHC4 for Predicting Risk of Distant Recurrence After Endocrine Therapy., Journal Of Clinical Oncology 2013 vol. 31 (22) pp. 2783-2790, Link »
Anita K Dunbier, Zara Ghazoui, Helen Anderson, Janine Salter, Ashutosh Nerurkar, Peter Osin, Roger A'hern, William R Miller, Ian E Smith, and Mitchell Dowsett, Molecular profiling of aromatase inhibitor-treated post-menopausal breast tumors identifies immune-related correlates of resistance., Clinical cancer research : an official journal of the American Association for Cancer Research May 15, 2013 19; 2775, Link »
Aleix Prat, Ana Lluch, Arran K Turnbull, Anita K Dunbier, Lourdes Calvo, Joan Albanell, Juan de la Haba-Rodríguez, Angels Arcusa, Ignacio Chacón, Pedro Sánchez-Rovira, Arrate Plazaola, Montse Muñoz, Laia Paré, Joel S Parker, Nuria Ribelles, Begona Jimenez, Abdul Aziz Bin Aiderus, Rosalía Caballero, Barbara Adamo, Mitch Dowsett, Eva M Carrasco, Miguel Martín, J Michael Dixon, Charles M Perou, and Emilio Alba., A PAM50-based Chemo-Endocrine Score for Hormone Receptor-Positive Breast Cancer with an Intermediate Risk of Relapse., Clin Cancer Res 2016., Link »
Weigel MT, Ghazoui Z, Dunbier A, Pancholi S, Dowsett M, Martin LA. Preclinical and clinical studies of estrogen deprivation support the PDGF/Abl pathway as a novel therapeutic target for overcoming endocrine resistance in breast cancer. Breast Cancer Res. 2012 May 18;14(3):R78.
Dunbier AK, Anderson H, Ghazoui Z, Lopez-Knowles E, Pancholi S, Ribas R, Drury S, Sidhu K, Leary A, Martin LA, Dowsett M. ESR1 is co-expressed with closely adjacent uncharacterised genes spanning a breast cancer susceptibility locus at 6q25.1. PLoS Genet. 2011 Apr;7(4):e1001382.
Dunbier AK, Anderson H, Ghazoui Z, Salter J, Parker JS, Perou CM, Smith IE, Dowsett M. Association between breast cancer subtypes and response to neoadjuvant anastrozole. Steroids. 2011 Jul;76(8):736-40.
Ghazoui Z, Buffa FM, Dunbier AK, Anderson H, Dexter T, Detre S, Salter J, Smith IE, Harris AL, Dowsett M. Close and stable relationship between proliferation and a hypoxia metagene in aromatase inhibitor-treated ER-positive breast cancer. Clin Cancer Res. 2011 May 1;17(9):3005-12.
Miller TW, Balko JM, Fox EM, Ghazoui Z, Dunbier A, Anderson H, Dowsett M, Jiang A, Smith RA, Maira SM, Manning HC, González-Angulo AM, Mills GB, Higham C, Chanthaphaychith S, Kuba MG, Miller WR, Shyr Y, Arteaga CL. ER?-dependent E2F transcription can mediate resistance to estrogen deprivation in human breast cancer. Cancer Discov. 2011 Sep;1(4):338-351.
Miller TW, Balko JM, Ghazoui Z, Dunbier A, Anderson H, Dowsett M, González-Angulo AM, Mills GB, Miller WR, Wu H, Shyr Y, Arteaga CL. A gene expression signature from human breast cancer cells with acquired hormone independence identifies MYC as a mediator of antiestrogen resistance. Clin Cancer Res. 2011 Apr 1;17(7):2024-34.
Dowsett M, Smith I, Robertson J, Robison L, Pinhel I, Johnson L, Salter J, Dunbier A, Anderson H, Ghazoui Z, Skene T, Evans A, A'Hern R, Iskender A, Wilcox M, Bliss J. Endocrine therapy, new biologicals, and new study designs for presurgical studies in breast cancer. J Natl Cancer Inst Monogr. 2011;2011(43):120-3.
Dunbier AK, Martin LA, Dowsett M. New and translational perspectives of oestrogen deprivation in breast cancer. Mol Cell Endocrinol. 2011 Jul 4;340(2):137-41.
Lønning PE, Haynes BP, Straume AH, Dunbier A, Helle H, Knappskog S, Dowsett M. Exploring breast cancer estrogen disposition: the basis for endocrine manipulation. Clin Cancer Res. 2011 Aug 1;17(15):4948-58.
Martin LA, Ghazoui Z, Weigel MT, Pancholi S, Dunbier A, Johnston S, Dowsett M. An in vitro model showing adaptation to long-term oestrogen deprivation highlights the clinical potential for targeting kinase pathways in combination with aromatase inhibition. Steroids. 2011 Jul;76(8):772-6.
Lønning PE, Haynes BP, Straume AH, Dunbier A, Helle H, Knappskog S, Dowsett M. Recent data on intratumor estrogens in breast cancer. Steroids. 2011 Jul;76(8):786-91.
Dowsett M, Cuzick J, Wale C, Forbes J, Mallon EA, Salter J, Quinn E, Dunbier A, Baum M, Buzdar A, Howell A, Bugarini R, Baehner FL, Shak S. Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study. J Clin Oncol. 2010 Apr 10;28(11):1829-34.
Dunbier AK, Anderson H, Ghazoui Z, Folkerd EJ, A'hern R, Crowder RJ, Hoog J, Smith IE, Osin P, Nerurkar A, Parker JS, Perou CM, Ellis MJ, Dowsett M. Relationship between plasma estradiol levels and estrogen-responsive gene expression in estrogen receptor-positive breast cancer in postmenopausal women. J Clin Oncol. 2010 Mar 1;28(7):1161-7. Epub 2010 Feb 1.
Dunbier AK, Hong Y, Masri S, Brown KA, Sabnis GJ, Palomares MR. Progress in aromatase research and identification of key future directions. J Steroid Biochem Mol Biol. 2010 Feb 28;118(4-5):311-5.