The London Research Institute research groups are based at Lincoln’s Inn Fields and Clare Hall. Our major research themes are: the biology of tumours and tissues, cellular regulatory mechanisms and genomic integrity and cell cycle.
Charles Swanton : Translational Cancer Therapeutics
Goals
The Translational Cancer Therapeutics (TCT) Laboratory is focused on identification of mechanisms of drug resistance and genomic instability in solid tumours. We are using parallel clinical trial and integrative functional genomics approaches to develop new predictive tools to enable the optimal stratification of patients for defined therapeutic approaches. Through work aimed at identifying therapeutic approaches to target distinct patterns of genome instability, the TCT laboratory has demonstrated that chromosomal instability appears to be one of the principal drivers of multi-drug resistance and poor prognosis in solid tumours. The laboratory is now focusing on 1) A greater understanding of the molecular basis of the origins of intratumour heterogeneity, with a principal focus on Structural and Numerical Chromosomal Instability in solid tumours in order to attempt to limit the acquisition of multi-drug resistance and treatment failure and 2) An in-depth understanding of the prevalence and prognostic impact of intratumour heterogeneity in lung and kindey cancer.
Selected Papers
Gerlinger M, Santos CR, Spencer-Dene B, Martinez P, Endesfelder D, Burrell RA, Vetter M, Jiang M, Saunders RE, Kelly G, Rioux-Leclercq N, Stamp G, Patard JJ, Larkin J, Howell M, Swanton C. Genome-wide RNA interference analysis of renal carcinoma survival regulators identifies MCT4 as a Warburg effect metabolic target. J Pathol. 2012 Feb 24. doi: 10.1002/path.4006. [Epub ahead of print]
(Abstract)
Lee A., Roylance R., Sander J., Gorman P., Endesfelder D., Kschischo M., Jones N.P., East P., Nicke B., Spassieva S., Obeid L., Birkbak N., Szalassi Z., Mcknight N.C., Rowan A., Speirs V., Hanby A., Downward J., Swanton C*. CERT depletion predicts chemotherapy benefit and mediates cytotoxic and polyploid-specific cancer cell death through autophagy induction. Journal of Pathology 2012 Feb;226(3):482-94
(Abstract)
Birkbak NJ, Eklund AC, Li Q, McClelland SE, Endesfelder D, Tan P, Tan IB, Richardson AL, Szallasi Z, Swanton C. Paradoxical Relationship Between Chromosomal Instability and Survival Outcome in Cancer. Cancer Res. 2011;71(10):3447-3452
(Abstract)
Lee AJ, Endesfelder D, Rowan AJ, Walther A, Birkbak NJ, Futreal PA, Downward J, Szallasi Z, Tomlinson IP, Howell M, Kschischo M, Swanton C. Chromosomal Instability Confers Intrinsic Multidrug Resistance. Cancer Res. 2011;71 (5):1858-1870
(Abstract)
Roylance R, Endesfelder D, Gorman P, Burrell RA, Sander J, Tomlinson I, Hanby AM, Speirs V, Richardson AL, Birkbak NJ, Eklund AC, Downward J, Szallasi Z, Kschischo M, Swanton C. Relationship of Extreme Chromosomal Instability with Long-term Survival in a Retrospective Analysis of Primary Breast Cancer. Cancer Epidemiol Biomarkers Prev. 2011;20(10):2183-94.
(Abstract)
Juul N., Eklund A., Li Q., Burrell R.A., Valero V., Andreopoulou E., Esteva F.J., Symmans W.F, Desmedt C., Haibe-Kains B., Sotiriou C., Pusztai L., Szallasi Z. and Swanton C* (2010) * corresponding author. Evaluation of an RNA interference screen-derived mitotic and ceramide pathway metagene in paclitaxel-treated primary ER-/PR-/ERBB2- breast cancer: a retrospective analysis of five clinical trials. (2010) Lancet Oncology 11(4):358-65
(Abstract)
Li Q, Eklund AC, Juul N, Haibe-Kains B, Workman CT, Richardson AL, Szallasi Z, Swanton C. Minimising Immunohistochemical False Negative ER Classification Using a Complementary 23 Gene Expression Signature of ER status. PLOS One. 2010;5(12):e15031
(Abstract)
Swanton C, Nicke B, Schuett M, Eklund AC, Ng C, Li Q, Hardcastle T, Lee A, Roy R, East P, Kschischo M, Endesfelder D, Wylie P, Kim SN, Chen JG, Howell M, Ried T, Habermann JK, Auer G, Brenton JD, Szallasi Z, Downward J. Chromosomal Instability determines taxane response. Proc Natl Acad Sci U S A. 2009;106(21):8671-6
(Abstract)
Lee AJ, East P, Pepper S, Nicke B, Szallasi Z, Eklund AC, Downward J, Swanton C. Concordance of exon array and real time PCR assessment of gene expression following cancer cell cytotoxic drug exposure. Cell Cycle. 2008;7(24):3947-8
(Abstract)
Swanton C, Nicke B, Marani M, Kelly G, Downward J. Initiation of high frequency multi-drug resistance following kinase targeting by siRNAs. Cell Cycle. 2007;6(16):2001-4
(Abstract)
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Charles Swanton
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