Jacqui Shaw - Academia.edu (original) (raw)

Papers by Jacqui Shaw

Journal of Clinical Oncology, 2011

555 Background: Early detection and monitoring the progress of common cancers is a continuing pro... more 555 Background: Early detection and monitoring the progress of common cancers is a continuing problem. Patients with cancer are known to have cancer-derived DNA circulating free in plasma (cfDNA) and we hypothesised that this may form the basis for a means of detecting and monitoring the disease Methods: For the first time, we have characterised cfDNA of breast cancer patients to create a molecular portrait, using high resolution analysis with Affymetrix SNP 6.0 Arrays. This array features 906,600 probes for single nucleotide polymorphisms (SNPs) and 946,000 probes for copy number variation (CNV) detection and represents more genetic variation on a single array than any other array platform. SNP 6.0 profiles of the primary tumour were compared with paired cfDNA samples of 50 breast cancer patients on follow-up after surgical removal of their primary tumour and related to cfDNA results of 15 primary breast cancer patients for whom we collected pre-surgical blood samples and healthy female controls. RESULTS Concordance of SNP genotype calls distinguished between breast cancer patients and healthy controls (p < 0.0001) and between pre-operative patients and patients on follow-up who had surgery and treatment (p = 0.002). Principal component analysis of plasma SNP/copy number results also separated 15 pre-surgical breast cancer patients from the healthy controls suggesting CNVs in plasma DNA have clinical significance. In the 50 patients on follow-up specific CNVs were detected in plasma, mirroring the primary tumour, up to 10 years after diagnosis despite no other evidence of disease on routine scanning. Finally, we identified focal high level DNA amplification, clustered at 7 chromosome arms, amenable to high throughput approaches for screening and monitoring. CONCLUSIONS This study clearly demonstrates the potential of SNP/CNV analysis of cfDNA to reliably distinguish between patients with primary breast cancer and healthy controls, and for monitoring patients after the completion of surgery, radiation therapy and chemotherapy. Our findings may also apply to other cancers where early detection is essential for cure and dormancy is a feature.

Annals of Oncology, 2012

ABSTRACT Background Inhibition of Hsp90, a key molecular chaperone required for activation of man... more ABSTRACT Background Inhibition of Hsp90, a key molecular chaperone required for activation of many oncoproteins, can lead to cancer cell death. Ganetespib (G) is an Hsp90 inhibitor that has shown single agent activity in molecularly defined disease, including ELM4-ALK rearrangement, KRAS mutations, HER2 amplification and BRAF mutations. Circulating free DNA (cfDNA) is present at low levels in plasma of healthy individuals, whereas its increased concentration was observed in patients with malignant tumors including non-small cell lung cancer (NSCLC). Cancer gene somatic mutations can be detected in cfDNA. Methods This is a randomized trial, comparing G+ docetaxel (D), to D in 2nd line advanced NSCLC patients. This study aimed at investigating the potential usefulness of plasma DNA concentration in NSCLC patients for efficacy of therapy. We performed a prospective exploratory analysis to identify serum biomarkers as predictors of improved outcomes with G. Plasma samples were collected from 160 pts at baseline prior to initiation of treatment, and at end of cycles 1 and 2. cfDNA was evaluated using the Ion Torrent platform to survey mutations in 46 cancer genes. Serum levels were correlated with progression free survival (PFS) and overall survival (OS) in both treatment arms. Upfront enrichment using both nanoparticle capture and phosphoprotein capture technologies were coupled to high resolution Orbitrap-LTQ MS/MS analysis followed by spectral counting for each samples. Results By early May approximately half of the 300 planned patients were enrolled. Baseline characteristics were balanced. Full proteomic profiling and cfDNA analysis is ongoing, and will be correlated with the efficacy outcomes from a planned interim analysis in early September, including disease control rate, PFS, and OS. Disclosure I. El Hariry: stock ownership. V. Vukovic: stock ownership. F. Teofilovici: stock option. V. Reichert: stock options. All other authors have declared no conflicts of interest.

TPS600Background: Neoadjuvant chemotherapy (NACT) results in eradication of cancer in the axillar... more TPS600Background: Neoadjuvant chemotherapy (NACT) results in eradication of cancer in the axillary nodes in 40% to 70% of patients. This raises questions about the benefit of further axillary treat...

IEEE Transactions on Biomedical Circuits and Systems, 2021

ESR1 mutations are important biomarkers in metastatic breast cancer. Specifically, p.E380Q and p.... more ESR1 mutations are important biomarkers in metastatic breast cancer. Specifically, p.E380Q and p.Y537S mutations arise in response to hormonal therapies given to patients with hormone receptor positive (HR+) breast cancer (BC). This paper demonstrates the efficacy of an ISFET based CMOS integrated Lab-on-Chip (LoC) system, coupled with variant-specific isothermal amplification chemistries, for detection and discrimination of wild type (WT) from mutant (MT) copies of the ESR1 gene. Hormonal resistant cancers often lead to increased chances of metastatic disease which leads to high mortality rates, especially in low-income regions and areas with low healthcare coverage. Design and optimization of bespoke primers was carried out and tested on a qPCR instrument and then benchmarked versus the LoC platform. Assays for detection of p.Y537S and p.E380Q were developed and tested on the LoC platform, achieving amplification in under 25 minutes and sensitivity of down to 1000 copies of DNA pe...

This study demonstrates the diagnostic performance of SARS-CoV-2 RT-LAMP assays, comparing the pe... more This study demonstrates the diagnostic performance of SARS-CoV-2 RT-LAMP assays, comparing the performance of genomic versus sub-genomic sequence target with subsequent application in an asymptomatic screening population. An RT-LAMP workflow was developed using synthetic positive control RNA and the diagnostic sensitivity and specificity was then determined using clinical patient samples processed through the diagnostic RT-PCR service within the University Hospitals of Leicester NHS Trust. 92 RT-PCR clinically positive and 88 RT-PCR clinically negative swab samples along with 78 clinically positive and 63 clinically negative saliva samples were equally detected at 100% DSe and 100% DSp for all samples reporting a Ct < 20. DSe for all samples reporting a Ct < 30 reduced slightly to around 95% (100% DSp) for both the single genomic (large open reading frame; orf1a) and dual sub-genomic (nucleocapsid plus envelope) targeting RT-LAMP assays. Lastly, the diagnostic performance of a...

Nature Communications

Malignant Pleural Mesothelioma (MPM) is typically diagnosed 20–50 years after exposure to asbesto... more Malignant Pleural Mesothelioma (MPM) is typically diagnosed 20–50 years after exposure to asbestos and evolves along an unknown evolutionary trajectory. To elucidate this path, we conducted multi-regional exome sequencing of 90 tumour samples from 22 MPMs acquired at surgery. Here we show that exomic intratumour heterogeneity varies widely across the cohort. Phylogenetic tree topology ranges from linear to highly branched, reflecting a steep gradient of genomic instability. Using transfer learning, we detect repeated evolution, resolving 5 clusters that are prognostic, with temporally ordered clonal drivers. BAP1/−3p21 and FBXW7/-chr4 events are always early clonal. In contrast, NF2/−22q events, leading to Hippo pathway inactivation are predominantly late clonal, positively selected, and when subclonal, exhibit parallel evolution indicating an evolutionary constraint. Very late somatic alteration of NF2/22q occurred in one patient 12 years after surgery. Clonal architecture and evol...

Clinical Research (Excluding Clinical Trials)

Nature Medicine

In the version of this article initially published, the list of members and affiliations for the ... more In the version of this article initially published, the list of members and affiliations for the TRACERx Consortium was provided as a Supplementary Note. The list should have been provided in the online version. The error has been corrected in the HTML and PDF versions of the article.

Clinical Research (Excluding Clinical Trials)

Background: Circulating tumor DNA (ctDNA) is emerging as a valuable less-invasive adjunct to tiss... more Background: Circulating tumor DNA (ctDNA) is emerging as a valuable less-invasive adjunct to tissue biopsy for real time monitoring and personalization of cancer treatment. This study aimed to determine the prognostic value of baseline ctDNA in both early and advanced gastroesophageal adenocarcinoma (GEA) and establish whether dynamic changes in ctDNA provides useful response and prognosis information. Patients and Methods: Formalin-fixed, paraffin-embedded (FFPE) tissue DNA and serial plasma cell-free DNA (cfDNA) were obtained from 36 patients (23 early stage (63.9%), 13 advanced stage (36.1%)) undergoing treatment for GEA. Tumor DNA was analyzed by targeted next generation sequencing (NGS) (custom ampliseq six gene panel) and Nanostring™ nCounter® technology (87 gene panel). In each patient, selected mutations and gene amplifications were profiled in serial cfDNA samples using a combination of NGS, droplet digital PCR and real-time quantitative PCR. Results: Mutations and/or gene amplifications were identified in tumor DNA of 33/36 patients (91.7%). Patient specific profiling detected ctDNA in 19/33 patients (57.6%) at baseline: 9/22 with early stage disease (40.9%) and 10/11 with advanced stage disease (90.9%). Objective Response Rate (ORR) by RECIST 1.1 criteria was 71.4% (10/14) for patients who were ctDNA negative at baseline (group A) and 52.9% (9/17) for patients with detectable ctDNA at baseline (group B). Multivariate Cox regression analysis, adjusted for stage of disease and patient performance status, showed presence of ctDNA at baseline was associated with both reduced progression free survival (PFS) and overall survival (OS) [hazard ratio (HR) of 6.2 (95% CI 1.9-19.8, P = 0.002) and 7.3 (CI 1.9-28.2, P = 0.004), respectively]. The median PFS was 34.7 months and 12.1 months and median OS was not reached and 14.5 months for group A and B, respectively (Mantel-Cox Log Rank P = 0.008 and P Citation Format: Ali Abdulnabi Mohamed, Mark R. Openshaw, Barbara Ottolini, David Guttery, Daniel Fernandez Garcia, Cathy J. Richards, Jacqui A. Shaw, Anne L. Thomas. The role of baseline and early dynamics of ctDNA in predicting response and prognosis of early and advanced gastroesophageal adenocarcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2281.

Nature Reviews Clinical Oncology

Cell death & disease, Jan 30, 2018

Improving early detection of colorectal cancer (CRC) is a key public health priority as adenomas ... more Improving early detection of colorectal cancer (CRC) is a key public health priority as adenomas and stage I cancer can be treated with minimally invasive procedures. Population screening strategies based on detection of occult blood in the feces have contributed to enhance detection rates of localized disease, but new approaches based on genetic analyses able to increase specificity and sensitivity could provide additional advantages compared to current screening methodologies. Recently, circulating cell-free DNA (cfDNA) has received much attention as a cancer biomarker for its ability to monitor the progression of advanced disease, predict tumor recurrence and reflect the complex genetic heterogeneity of cancers. Here, we tested whether analysis of cfDNA is a viable tool to enhance detection of colon adenomas. To address this, we assessed a cohort of patients with adenomas and healthy controls using droplet digital PCR (ddPCR) and mutation-specific assays targeted to trunk mutatio...

Cancer cell, Jan 9, 2018

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that a... more With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8 to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches.

BMC cancer, Jan 23, 2017

The presence of circulating cell-free DNA from tumours in blood (ctDNA) is of major importance to... more The presence of circulating cell-free DNA from tumours in blood (ctDNA) is of major importance to those interested in early cancer detection, as well as to those wishing to monitor tumour progression or diagnose the presence of activating mutations to guide treatment. In 2014, the UK Early Cancer Detection Consortium undertook a systematic mapping review of the literature to identify blood-based biomarkers with potential for the development of a non-invasive blood test for cancer screening, and which identified this as a major area of interest. This review builds on the mapping review to expand the ctDNA dataset to examine the best options for the detection of multiple cancer types. The original mapping review was based on comprehensive searches of the electronic databases Medline, Embase, CINAHL, the Cochrane library, and Biosis to obtain relevant literature on blood-based biomarkers for cancer detection in humans (PROSPERO no. CRD42014010827). The abstracts for each paper were rev...

Journal of Clinical Oncology, 2011

555 Background: Early detection and monitoring the progress of common cancers is a continuing pro... more 555 Background: Early detection and monitoring the progress of common cancers is a continuing problem. Patients with cancer are known to have cancer-derived DNA circulating free in plasma (cfDNA) and we hypothesised that this may form the basis for a means of detecting and monitoring the disease Methods: For the first time, we have characterised cfDNA of breast cancer patients to create a molecular portrait, using high resolution analysis with Affymetrix SNP 6.0 Arrays. This array features 906,600 probes for single nucleotide polymorphisms (SNPs) and 946,000 probes for copy number variation (CNV) detection and represents more genetic variation on a single array than any other array platform. SNP 6.0 profiles of the primary tumour were compared with paired cfDNA samples of 50 breast cancer patients on follow-up after surgical removal of their primary tumour and related to cfDNA results of 15 primary breast cancer patients for whom we collected pre-surgical blood samples and healthy female controls. RESULTS Concordance of SNP genotype calls distinguished between breast cancer patients and healthy controls (p < 0.0001) and between pre-operative patients and patients on follow-up who had surgery and treatment (p = 0.002). Principal component analysis of plasma SNP/copy number results also separated 15 pre-surgical breast cancer patients from the healthy controls suggesting CNVs in plasma DNA have clinical significance. In the 50 patients on follow-up specific CNVs were detected in plasma, mirroring the primary tumour, up to 10 years after diagnosis despite no other evidence of disease on routine scanning. Finally, we identified focal high level DNA amplification, clustered at 7 chromosome arms, amenable to high throughput approaches for screening and monitoring. CONCLUSIONS This study clearly demonstrates the potential of SNP/CNV analysis of cfDNA to reliably distinguish between patients with primary breast cancer and healthy controls, and for monitoring patients after the completion of surgery, radiation therapy and chemotherapy. Our findings may also apply to other cancers where early detection is essential for cure and dormancy is a feature.

Annals of Oncology, 2012

ABSTRACT Background Inhibition of Hsp90, a key molecular chaperone required for activation of man... more ABSTRACT Background Inhibition of Hsp90, a key molecular chaperone required for activation of many oncoproteins, can lead to cancer cell death. Ganetespib (G) is an Hsp90 inhibitor that has shown single agent activity in molecularly defined disease, including ELM4-ALK rearrangement, KRAS mutations, HER2 amplification and BRAF mutations. Circulating free DNA (cfDNA) is present at low levels in plasma of healthy individuals, whereas its increased concentration was observed in patients with malignant tumors including non-small cell lung cancer (NSCLC). Cancer gene somatic mutations can be detected in cfDNA. Methods This is a randomized trial, comparing G+ docetaxel (D), to D in 2nd line advanced NSCLC patients. This study aimed at investigating the potential usefulness of plasma DNA concentration in NSCLC patients for efficacy of therapy. We performed a prospective exploratory analysis to identify serum biomarkers as predictors of improved outcomes with G. Plasma samples were collected from 160 pts at baseline prior to initiation of treatment, and at end of cycles 1 and 2. cfDNA was evaluated using the Ion Torrent platform to survey mutations in 46 cancer genes. Serum levels were correlated with progression free survival (PFS) and overall survival (OS) in both treatment arms. Upfront enrichment using both nanoparticle capture and phosphoprotein capture technologies were coupled to high resolution Orbitrap-LTQ MS/MS analysis followed by spectral counting for each samples. Results By early May approximately half of the 300 planned patients were enrolled. Baseline characteristics were balanced. Full proteomic profiling and cfDNA analysis is ongoing, and will be correlated with the efficacy outcomes from a planned interim analysis in early September, including disease control rate, PFS, and OS. Disclosure I. El Hariry: stock ownership. V. Vukovic: stock ownership. F. Teofilovici: stock option. V. Reichert: stock options. All other authors have declared no conflicts of interest.

TPS600Background: Neoadjuvant chemotherapy (NACT) results in eradication of cancer in the axillar... more TPS600Background: Neoadjuvant chemotherapy (NACT) results in eradication of cancer in the axillary nodes in 40% to 70% of patients. This raises questions about the benefit of further axillary treat...

IEEE Transactions on Biomedical Circuits and Systems, 2021

ESR1 mutations are important biomarkers in metastatic breast cancer. Specifically, p.E380Q and p.... more ESR1 mutations are important biomarkers in metastatic breast cancer. Specifically, p.E380Q and p.Y537S mutations arise in response to hormonal therapies given to patients with hormone receptor positive (HR+) breast cancer (BC). This paper demonstrates the efficacy of an ISFET based CMOS integrated Lab-on-Chip (LoC) system, coupled with variant-specific isothermal amplification chemistries, for detection and discrimination of wild type (WT) from mutant (MT) copies of the ESR1 gene. Hormonal resistant cancers often lead to increased chances of metastatic disease which leads to high mortality rates, especially in low-income regions and areas with low healthcare coverage. Design and optimization of bespoke primers was carried out and tested on a qPCR instrument and then benchmarked versus the LoC platform. Assays for detection of p.Y537S and p.E380Q were developed and tested on the LoC platform, achieving amplification in under 25 minutes and sensitivity of down to 1000 copies of DNA pe...

This study demonstrates the diagnostic performance of SARS-CoV-2 RT-LAMP assays, comparing the pe... more This study demonstrates the diagnostic performance of SARS-CoV-2 RT-LAMP assays, comparing the performance of genomic versus sub-genomic sequence target with subsequent application in an asymptomatic screening population. An RT-LAMP workflow was developed using synthetic positive control RNA and the diagnostic sensitivity and specificity was then determined using clinical patient samples processed through the diagnostic RT-PCR service within the University Hospitals of Leicester NHS Trust. 92 RT-PCR clinically positive and 88 RT-PCR clinically negative swab samples along with 78 clinically positive and 63 clinically negative saliva samples were equally detected at 100% DSe and 100% DSp for all samples reporting a Ct < 20. DSe for all samples reporting a Ct < 30 reduced slightly to around 95% (100% DSp) for both the single genomic (large open reading frame; orf1a) and dual sub-genomic (nucleocapsid plus envelope) targeting RT-LAMP assays. Lastly, the diagnostic performance of a...

Nature Communications

Malignant Pleural Mesothelioma (MPM) is typically diagnosed 20–50 years after exposure to asbesto... more Malignant Pleural Mesothelioma (MPM) is typically diagnosed 20–50 years after exposure to asbestos and evolves along an unknown evolutionary trajectory. To elucidate this path, we conducted multi-regional exome sequencing of 90 tumour samples from 22 MPMs acquired at surgery. Here we show that exomic intratumour heterogeneity varies widely across the cohort. Phylogenetic tree topology ranges from linear to highly branched, reflecting a steep gradient of genomic instability. Using transfer learning, we detect repeated evolution, resolving 5 clusters that are prognostic, with temporally ordered clonal drivers. BAP1/−3p21 and FBXW7/-chr4 events are always early clonal. In contrast, NF2/−22q events, leading to Hippo pathway inactivation are predominantly late clonal, positively selected, and when subclonal, exhibit parallel evolution indicating an evolutionary constraint. Very late somatic alteration of NF2/22q occurred in one patient 12 years after surgery. Clonal architecture and evol...

Clinical Research (Excluding Clinical Trials)

Nature Medicine

In the version of this article initially published, the list of members and affiliations for the ... more In the version of this article initially published, the list of members and affiliations for the TRACERx Consortium was provided as a Supplementary Note. The list should have been provided in the online version. The error has been corrected in the HTML and PDF versions of the article.

Clinical Research (Excluding Clinical Trials)

Background: Circulating tumor DNA (ctDNA) is emerging as a valuable less-invasive adjunct to tiss... more Background: Circulating tumor DNA (ctDNA) is emerging as a valuable less-invasive adjunct to tissue biopsy for real time monitoring and personalization of cancer treatment. This study aimed to determine the prognostic value of baseline ctDNA in both early and advanced gastroesophageal adenocarcinoma (GEA) and establish whether dynamic changes in ctDNA provides useful response and prognosis information. Patients and Methods: Formalin-fixed, paraffin-embedded (FFPE) tissue DNA and serial plasma cell-free DNA (cfDNA) were obtained from 36 patients (23 early stage (63.9%), 13 advanced stage (36.1%)) undergoing treatment for GEA. Tumor DNA was analyzed by targeted next generation sequencing (NGS) (custom ampliseq six gene panel) and Nanostring™ nCounter® technology (87 gene panel). In each patient, selected mutations and gene amplifications were profiled in serial cfDNA samples using a combination of NGS, droplet digital PCR and real-time quantitative PCR. Results: Mutations and/or gene amplifications were identified in tumor DNA of 33/36 patients (91.7%). Patient specific profiling detected ctDNA in 19/33 patients (57.6%) at baseline: 9/22 with early stage disease (40.9%) and 10/11 with advanced stage disease (90.9%). Objective Response Rate (ORR) by RECIST 1.1 criteria was 71.4% (10/14) for patients who were ctDNA negative at baseline (group A) and 52.9% (9/17) for patients with detectable ctDNA at baseline (group B). Multivariate Cox regression analysis, adjusted for stage of disease and patient performance status, showed presence of ctDNA at baseline was associated with both reduced progression free survival (PFS) and overall survival (OS) [hazard ratio (HR) of 6.2 (95% CI 1.9-19.8, P = 0.002) and 7.3 (CI 1.9-28.2, P = 0.004), respectively]. The median PFS was 34.7 months and 12.1 months and median OS was not reached and 14.5 months for group A and B, respectively (Mantel-Cox Log Rank P = 0.008 and P Citation Format: Ali Abdulnabi Mohamed, Mark R. Openshaw, Barbara Ottolini, David Guttery, Daniel Fernandez Garcia, Cathy J. Richards, Jacqui A. Shaw, Anne L. Thomas. The role of baseline and early dynamics of ctDNA in predicting response and prognosis of early and advanced gastroesophageal adenocarcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2281.

Nature Reviews Clinical Oncology

Cell death & disease, Jan 30, 2018

Improving early detection of colorectal cancer (CRC) is a key public health priority as adenomas ... more Improving early detection of colorectal cancer (CRC) is a key public health priority as adenomas and stage I cancer can be treated with minimally invasive procedures. Population screening strategies based on detection of occult blood in the feces have contributed to enhance detection rates of localized disease, but new approaches based on genetic analyses able to increase specificity and sensitivity could provide additional advantages compared to current screening methodologies. Recently, circulating cell-free DNA (cfDNA) has received much attention as a cancer biomarker for its ability to monitor the progression of advanced disease, predict tumor recurrence and reflect the complex genetic heterogeneity of cancers. Here, we tested whether analysis of cfDNA is a viable tool to enhance detection of colon adenomas. To address this, we assessed a cohort of patients with adenomas and healthy controls using droplet digital PCR (ddPCR) and mutation-specific assays targeted to trunk mutatio...

Cancer cell, Jan 9, 2018

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that a... more With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8 to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches.

BMC cancer, Jan 23, 2017

The presence of circulating cell-free DNA from tumours in blood (ctDNA) is of major importance to... more The presence of circulating cell-free DNA from tumours in blood (ctDNA) is of major importance to those interested in early cancer detection, as well as to those wishing to monitor tumour progression or diagnose the presence of activating mutations to guide treatment. In 2014, the UK Early Cancer Detection Consortium undertook a systematic mapping review of the literature to identify blood-based biomarkers with potential for the development of a non-invasive blood test for cancer screening, and which identified this as a major area of interest. This review builds on the mapping review to expand the ctDNA dataset to examine the best options for the detection of multiple cancer types. The original mapping review was based on comprehensive searches of the electronic databases Medline, Embase, CINAHL, the Cochrane library, and Biosis to obtain relevant literature on blood-based biomarkers for cancer detection in humans (PROSPERO no. CRD42014010827). The abstracts for each paper were rev...