In the Sarah-Jane Dawson laboratory, researchers aim to develop improved molecular biomarkers for early detection, risk stratification and disease monitoring in cancer.
A major focus of our research is the development of non-invasive blood-based biomarkers, to enable personalised disease monitoring and facilitate therapeutic decisions in both solid and haematological malignancies, and thereby improve patient outcomes.
Liquid biopsies for molecular disease monitoring in cancer
Many cancers shed small amounts of DNA, called circulating tumour DNA (ctDNA), into the patient's bloodstream (Figure 1). The measurement of ctDNA could potentially be used as a marker of response to therapy or disease progression. Through recent advances in genomic technologies, it is now possible to accurately measure small amounts of ctDNA in blood. Our laboratory is focused on developing ctDNA as a non-invasive "liquid biopsy" alternative to tissue biopsies for use in cancer diagnostics and management. We apply innovative and cutting-edge genomic platforms to the analysis of ctDNA, including digital PCR and next-generation sequencing. With this methodology, we use ctDNA analysis to study clonal evolution and treatment resistance in cancer. We also study ctDNA as a clinical tool for molecular disease monitoring across a range of malignancies (Figure 2).
Understanding the genomic heterogeneity of circulating tumour cells
The development of metastatic disease remains the most significant challenge in the treatment of cancer patients and is responsible for the vast majority of cancer deaths. Blood represents the haematogenous route for tumour dissemination, yet little is known about the molecular characteristics of circulating tumour cells (CTCs) that seed distant disease metastatic sites (Figure 1). We use unique in vivo models derived from patient CTCs and innovative single-cell genomics tools to study genomic heterogeneity within CTCs, to gain a greater understanding of the biology of the metastatic process. This approach also provides a novel platform for us to test responses to standard and emerging therapies.
Murtaza M*, Dawson SJ*, Pogrebniak K, Rueda OM, Provenzano E, Grant J, Chin SF, Tsui DW, Marass F, Gale D, Ali HR, Shah P, Contente-Cuomo T, Farahani H, Shumansky K, Kingsbury Z, Humphray S, Bentley D, Shah SP, Wallis M, Rosenfeld N and Caldas C (2015). Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer. Nat Commun.Nov 4; 6:8760. (* Equal contribution)
Ignatiadis M and Dawson SJ (2014). Circulating tumor cells and circulating tumor DNA for precision medicine: dream or reality? Ann Oncol.25(12):2304-13.
Bidard FC, Peeters DJ, Fehm T, Nolé F, Gisbert-Criado R, Mavroudis D, Grisanti S, Generali D, Garcia-Saenz JA, Stebbing J, Caldas C, Gazzaniga P, Manso L, Zamarchi R, de Lascoiti AF, De Mattos-Arruda L, Ignatiadis M, Lebofsky R, van Laere SJ, Meier-Stiegen F, Sandri MT, Vidal-Martinez J, Politaki E, Consoli F, Bottini A, Diaz-Rubio E, Krell J, Dawson SJ, Raimondi C, Rutten A, Janni W, Munzone E, Carañana V, Agelaki S, Almici C, Dirix L, Solomayer EF, Zorzino L, Johannes H, Reis-Filho JS, Pantel K, Pierga JY and Michiels S (2014). Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol.15(4):406-14.
Dawson SJ*, Tsui DWY*, Murtaza M, Biggs H, Rueda OM, Chin SF, Dunning MJ, Gale D, Forshew T, Mahler-Araujo B, Rajan S, Humphray S, Becq J, Halsall D, Wallis M, Bentley D, Caldas C and Rosenfeld N (2013). Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med.368(13):1199-209. (* Equal contribution)
Murtaza M*, Dawson SJ*, Tsui DWY*, Gale D, Forshew T, Piskorz AM, Parkinson C, Chin SF, Kingsbury Z, Wong ASC, Marass F, Humphray S, Hadfield J, Bentley D, Chin TM, Brenton JD, Caldas C and Rosenfeld N (2013). Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature.497(7447):108-12. (* Equal contribution)
Dawson SJ, Rueda OM, Aparicio S and Caldas C (2013). A new genome-driven integrated classification of breast cancer and its implications. EMBO J.32(5):617-28.