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 and other metabolic pathways modified within cancer cells are being developed. The role and functions of several Fanconi Anaemia proteins 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.
|Sarah Taylor||PhD student||Email Sarah Taylor|
- Professor Mark Arends, University of Edinburgh
Professor David Argyle, University of Edinburgh
Professor Ian Kunkler, University of Edinburgh
Dr Arran Turnbull, University of Edinburgh
Professor David Harrison, University of St Andrews
Professor Charlie Gourley, University of Edinburgh
Langdon SP, Herrington CS, Hollis R, Gourley C, "Estrogen signaling and its potential as a target for therapy in ovarian cancer", Cancers 2020 Jun 22;12(6):1647. doi: 10.3390/cancers12061647. PMID: 32580290; PMCID: PMC7352420.
Taylor SJ, Arends MJ, Langdon SP, "Inhibitors of the Fanconi Anaemia pathway as potential antitumour agents for ovarian cancer", Exploration of Targeted Anti-tumor Therapy 2020;1(1):26-52. doi: 10.37349/etat.2020.00003. Epub 2020 Feb 29. PMID: 36046263; PMCID: PMC9400734.
Langdon SP, Kay C, Um IH, Dodds M, Muir M, Sellar G, Kan J, Gourley C, Harrison DJ, "Evaluation of the dual mTOR / PI3K inhibitors Gedatolisib (PF-05212384) and PF-04691502 against ovarian cancer xenograft models", Scientific Reports 2019 Dec 10;9(1):18742. doi: 10.1038/s41598-019-55096-9. PMID: 31822716; PMCID: PMC6904563.
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 2019 Jan 22;21(1):10. doi: 10.1186/s13058-019-1097-0. PMID: 30670058; PMCID: PMC6343358.
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. 2018 Jun 5;18(1):636. doi: 10.1186/s12885-018-4521-4. PMID: 29866066; PMCID: PMC5987622..
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. 2017 Jun 27;8(26):42857-42875. doi: 10.18632/oncotarget.17143. PMID: 28476026; PMCID: PMC5522111.
Langdon SP, Gourley C, Gabra H, Stanley B, "Endocrine Therapy in Ovarian Cancer", Expert Reviews of Anticancer Therapy 2017 Feb;17(2):109-117. doi: 10.1080/14737140.2017.1272414. Epub 2016 Dec 24. PMID: 27967255.
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, https://doi.org/10.1038/bjc.2016.6
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. 2015 Sep 22;6(28):24856-70. doi: 10.18632/oncotarget.4498. PMID: 26259239; PMCID: PMC4694798.
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. doi: 10.1016/j.ygyno.2013.07.099. Epub 2013 Jul 30. 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. doi: 10.1002/path.3980. Epub 2012 Feb 9. 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. doi: 10.1158/1078-0432.CCR-10-2461. Epub 2011 May 13. PMID: 21571868.