Dr Simon Langdon
Cancer is characterised by changes in cellular signalling pathways that regulate growth, survival, differentiation and invasion. We are seeking to improve the treatment of ovarian and breast cancer by developing therapeutic strategies that target the oestrogen receptor (ER), erbB / HER and DNA repair pathways and their related signalling pathways more effectively. Individual cancers have differing degrees of dependency on these pathways and we are investigating the associations between cell signalling via these receptors and cell fate; specifically linkage between pathway activation and outcomes such as growth, apoptosis and migration. We are characterising relevant subgroups of cancers amenable to appropriate therapeutic interventions based on specific inhibitors i.e. moving towards more personalised patient / tumour treatment. As part of this we are evaluating new inhibitors in preclinical models. We are also seeking to improve the use of radiotherapy in breast cancer. One of the limitations to its effectiveness is the development of hypoxia in poorly vascularised regions of the tumour. To counteract this, strategies that target hypoxic regions are under investigation. Other metabolic pathways modified within cancer cells that might prove useful as targets are also being investigated.
Signalling within cancer cells is dynamic and can be complex and a static description is frequently limited. We are developing both experimental cancer models and systems biology approaches to describe and predict the effects of novel inhibitors on cell fate over time. The objective is to model signalling pathways in human cancer cells, to test these models experimentally and to integrate data from primary human cancers to identify new candidate targets and to suggest dynamic biomarkers that can then be validated pathologically and in clinical trials.
|Duniya Mosly||PhD student||+44 (0)131 651 8784||Email Duniya Mosly|
|Maria Bonello||PhD student||+44 (0)131 651 8784||Email Maria Bonello|
- University of Abertay
- University of St Andrews
- University of Dundee
- University of Florence
Jarman E, Ward C,Turnbull AK, Martinez-Perez C, Meehan J, Sims AH, Langdon SP. Human epidermal growth factor receptor 2 (HER2) regulation of hypoxia-inducible factor 2 (HIF-2) in breast cancer. Breast Cancer Research, 21: 10, 2019.
Xintaropoulou C, Ward C, Wise A, Queckborner S, Turnbull AK, Michie CO, Williams A, Rye T, Gourley C, Langdon SP. Expression of glycolytic enzymes in ovarian cancers and evaluation of the glycolytic pathway as a strategy for ovarian cancer treatment. BMC Cancer. 18: 636, 2018.
Meehan J, Ward C, Turnbull A, Bukowski-Wills J, Jarman A, Xintaropoulou, Martinez-Perez C, Gray M, Pearson M, Mullen P, Supuran CT, Carta F, Harrison DJ, Kunkler IH, Langdon SP. Inhibition of pH regulation as a therapeutic strategy in hypoxic human breast cancer cells. Oncotarget. 8;42857 – 42875, 2017.
Langdon SP, Gourley C, Gabra H, Stanley B. Endocrine Therapy in Ovarian Cancer. Expert Reviews of Anticancer Therapy. 17:109 – 117, 2017.
Martinez-Perez C, Turnbull AK, Ward C, Mullen P, Cook G, Meehan J, Jarman E, Thomson PIT, Campbell CJ, McPhail D, Harrison DJ, Langdon SP. Antitumour Activity of the Novel Flavonoid Oncamex in Preclinical Breast Cancer Models. British Journal of Cancer. 114: 905 – 916, 2016
Ward C, Meehan J, Mullen P, Supuran C, Dixon JM, Thomas JS, Winum JY, Lambin P, Dubois L, Pavathaneni NK, Jarman EJ, Renshaw L, Um IH, Kay C, Harrison DJ, Kunkler IH, Langdon SP. Evaluation of carbonic anhydrase IX as a therapeutic target for inhibition of breast cancer invasion and metastasis using a series of in vitro breast cancer models. Oncotarget. 6 : 24856 - 24570, 2015.
Argenta PA, Um I, Kay C, Harrison D, Faratian D, Sueblinvong T, Geller MA, Langdon SP. Predicting response to the anti-estrogen fulvestrant in recurrent ovarian cancer. Gynecol Oncol. 2013 Nov;131(2):368-73. PMID: 23911795
Ng CKY, Cooke SL, Howe K, Newman S, Batty EM, Pole JCM, Langdon SP, Edwards PAW, Brenton JD. The role of tandem duplicator phenotype in tumour evolution and platinum resistance in high-grade serous ovarian cancer. J Pathol. 2012 Apr;226(5):703-12. PMID: 22183581
Faratian D, Zweemer AJM, Nagumo Y, Sims AH, Muir M, Dodds M, Mullen P, Um I, Kay C, Hasmann M, Harrison DJ, Langdon SP. Trastuzumab and pertuzumab produce changes in morphology and estrogen receptor signalling in ovarian cancer xenografts revealing new treatment strategies.Clin Cancer Res. 2011 Jul 1;17(13):4451-61. PMID: 21571868