Circulating tumour DNA sequencing to determine therapeutic response and identify tumour heterogeneity in patients with paediatric solid tumours

Monitoring tumour burden and therapeutic response through analysis of circulating tumour DNA and extracellular RNA in multiple myeloma patients

Leukemia ◽

10.1038/s41375-019-0469-x ◽

2019 ◽

Vol 33 (8) ◽

pp. 2022-2033 ◽

Cited By ~ 13

Author(s):

Sridurga Mithraprabhu ◽

Rachel Morley ◽

Tiffany Khong ◽

Anna Kalff ◽

Krystal Bergin ◽

...

Keyword(s):

Multiple Myeloma ◽

Therapeutic Response ◽

Tumour Burden ◽

Extracellular Rna ◽

Circulating Tumour Dna

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Profiling tumour heterogeneity through circulating tumour DNA in patients with pancreatic cancer

Oncotarget ◽

10.18632/oncotarget.20250 ◽

2017 ◽

Vol 8 (50) ◽

pp. 87221-87233 ◽

Cited By ~ 15

Author(s):

Patricia Adamo ◽

Caroline M. Cowley ◽

Christopher P. Neal ◽

Vilas Mistry ◽

Karen Page ◽

...

Keyword(s):

Pancreatic Cancer ◽

Tumour Heterogeneity ◽

Circulating Tumour Dna

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Liquid Biopsy in Endometrial Cancer: New Opportunities for Personalized Oncology

International Journal of Molecular Sciences ◽

10.3390/ijms19082311 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2311 ◽

Cited By ~ 24

Author(s):

Laura Muinelo-Romay ◽

Carlos Casas-Arozamena ◽

Miguel Abal

Keyword(s):

Endometrial Cancer ◽

Liquid Biopsy ◽

Personalised Medicine ◽

Response To Therapy ◽

Diagnostic Tools ◽

Precision Oncology ◽

Tumour Heterogeneity ◽

Genomic Studies ◽

Personalized Oncology ◽

Circulating Tumour Dna

The identification of new molecular targets and biomarkers associated with high risk of recurrence and response to therapy represents one of the main clinical challenges in the management of advanced disease in endometrial cancer. In this sense, the field of liquid biopsy has emerged as a great revolution in oncology and is considered “the way” to reach personalised medicine. In this review, we discuss the promising but already relatively limited advances of liquid biopsy in endometrial cancer compared to other types of tumours like breast, colorectal or prostate cancer. We present recent data analysing circulating tumour material in minimally-invasive blood samples, but also in alternative forms of liquid biopsy like uterine aspirates. Proteomic and genomic studies focused on liquid-based uterine samples are resulting not only in optimal diagnostic tools but also in reliable approaches to address tumour heterogeneity. Likewise, circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) represent an opportunity for the correct stratification of patients, for the assessment of early recurrent disease or for the real-time monitoring of therapy responses. Appropriately designed studies and implementation in clinical trials will determine the value of liquid biopsy for precision oncology in endometrial cancer.

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Clinical application of circulating tumour DNA in assessment of therapeutic response in HPV positive oropharyngeal cancer

European Journal of Surgical Oncology ◽

10.1016/j.ejso.2020.11.216 ◽

2021 ◽

Vol 47 (2) ◽

pp. e27-e28

Author(s):

Lucy Li ◽

John Thomson ◽

Sophie Warlow ◽

Martyna Adamowicz ◽

Helen Thain ◽

...

Keyword(s):

Clinical Application ◽

Oropharyngeal Cancer ◽

Therapeutic Response ◽

Circulating Tumour Dna

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Mechanistic modelling of dynamic MRI data predicts that tumour heterogeneity decreases therapeutic response

British Journal of Cancer ◽

10.1038/sj.bjc.6605773 ◽

2010 ◽

Vol 103 (4) ◽

pp. 486-497 ◽

Cited By ~ 19

Author(s):

R Venkatasubramanian ◽

R B Arenas ◽

M A Henson ◽

N S Forbes

Keyword(s):

Therapeutic Response ◽

Dynamic Mri ◽

Tumour Heterogeneity ◽

Mechanistic Modelling

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Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients

Nature Communications ◽

10.1038/ncomms11815 ◽

2016 ◽

Vol 7 (1) ◽

Cited By ~ 275

Author(s):

Jacob J. Chabon ◽

Andrew D. Simmons ◽

Alexander F. Lovejoy ◽

Mohammad S. Esfahani ◽

Aaron M. Newman ◽

...

Keyword(s):

Lung Cancer ◽

Resistance Mechanism ◽

Growth Factor Receptor ◽

Resistance Mechanisms ◽

Egfr Inhibitor ◽

Tumour Heterogeneity ◽

Lung Cancer Patients ◽

Ctdna Analysis ◽

Inhibitor Resistance ◽

Circulating Tumour Dna

Abstract Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of patients after treatment with first-line inhibitors, indicating frequent intra-patient heterogeneity. Rociletinib resistance recurrently involves MET, EGFR, PIK3CA, ERRB2, KRAS and RB1. We describe a novel EGFR L798I mutation and find that EGFR C797S, which arises in ∼33% of patients after osimertinib treatment, occurs in <3% after rociletinib. Increased MET copy number is the most frequent rociletinib resistance mechanism in this cohort and patients with multiple pre-existing mechanisms (T790M and MET) experience inferior responses. Similarly, rociletinib-resistant xenografts develop MET amplification that can be overcome with the MET inhibitor crizotinib. These results underscore the importance of tumour heterogeneity in NSCLC and the utility of ctDNA-based resistance mechanism assessment.

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Imaging polymers, proteins and dna in aqueous solutions with the atomic force microscope

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100152136 ◽

1989 ◽

Vol 47 ◽

pp. 32-33

Author(s):

S.A.C. Gould ◽

B. Drake ◽

C.B. Prater ◽

A.L. Weisenhorn ◽

S.M. Lindsay ◽

...

Keyword(s):

Amino Acids ◽

Dna Sequencing ◽

Aqueous Solutions ◽

Atomic Force Microscope ◽

Piezoelectric Crystal ◽

Atomic Force ◽

Structure Of Molecules ◽

Optical Lever

The atomic force microscope (AFM) is an instrument that can be used to image many samples of interest in biology and medicine. Images of polymerized amino acids, polyalanine and polyphenylalanine demonstrate the potential of the AFM for revealing the structure of molecules. Images of the protein fibrinogen which agree with TEM images demonstrate that the AFM can provide topographical data on larger molecules. Finally, images of DNA suggest the AFM may soon provide an easier and faster technique for DNA sequencing.The AFM consists of a microfabricated SiO2 triangular shaped cantilever with a diamond tip affixed at the elbow to act as a probe. The sample is mounted on a electronically driven piezoelectric crystal. It is then placed in contact with the tip and scanned. The topography of the surface causes minute deflections in the 100 μm long cantilever which are detected using an optical lever.

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