An Investigation of Chromosomal Instability Survival Mechanisms in Cancer.
Professor Charles Swanton - Cancer Research UK, LRI
Description of Project:
Chromosomal instability (CIN) describes ongoing numerical and structural chromosomal aberrations in cancer cells, leading to intra-tumour heterogeneity and is frequently associated with polyploidy and aneuploidy. CIN is a frequent event in solid tumours and previous evidence has implicated CIN with acquired multidrug resistance, intrinsic taxane resistance and poor patient prognosis. In my project, I have attempted to explore mechanisms required for the initiation of CIN and the tolerance of this pattern of genome instability.
Lee AJ, Roylance R, Sander J, Gorman P, Endesfelder D, Kschischo M, Jones NP, East P, Nicke B, Spassieva S, Obeid LM, Birkbak NJ, Szallasi Z, McKnight NC, Rowan AJ, Speirs V, Hanby AM, Downward J, Tooze SA, Swanton C. CERT depletion predicts chemotherapy benefit and mediates cytotoxic and polyploid-specific cancer cell death through autophagy induction. J Pathol. 2012 Feb;226(3):482-94. doi: 10.1002/path.2998.
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 Mar 1;71(5):1858-70.
Azzato EM, Lee AJ, Teschendorff A, Ponder BA, Pharoah P, Caldas C, Maia AT. Common germ-line polymorphism of C1QA and breast cancer survival. Br J Cancer. 2010 Apr 13;102(8):1294-9.
Maia AT, Spiteri I, Lee AJ, O'Reilly M, Jones L, Caldas C, Ponder BA. Extent of differential allelic expression of candidate breast cancer genes is similar in blood and breast. Breast Cancer Res. 2009;11(6):R88.
Lee AJ, Kolesnick R, Swanton C. RNAi-mediated functional analysis of pathways influencing cancer cell drug resistance. Expert Rev Mol Med. 2009 May 21;11:e15.
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 May 26;106(21):8671-6.
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 Dec 15;7(24):3947-8.