Cancer treatment has changed radically with the introduction of targeted drugs guided by mutation testing. Alterations in genes have been validated as powerful predictive biomarkers in the management of various cancers where mutation testing is currently the standard to personalise treatment decisions. It is well documented that a broad spectrum of cancers release DNA into peripheral blood (ctDNA). There is a growing interest in use of ctDNA as a non-invasive biomarker to detect the presence of cancer, follow treatment response, gauge prognosis, and monitor for recurrence. Next Generation Sequencing (NGS) has revolutionised genomic exploration and is driving the implementation of precision diagnostics. However, the sensitivity and accuracy of current NGS methods is compromised by sequencing errors. This is a fundamental limitation, particularly when aiming to identify rare mutants in genetically heterogeneous mixtures, such as ctDNA. To overcome this limitation, GeneFirst has developed an improved NGS technology with increased sensitivity and accuracy for the concurrent detection of multiple mutations. This new technology is suitable for the use of liquid biopsy (i.e. blood), enabling clinically relevant cancer genotyping by non-invasive means.

Cancer treatment has been changed radically by the introduction of targeted drugs, guided by mutation testing. Alterations in genes (gene mutations) have been validated as powerful predictive biomarkers in the management of various cancers and mutation testing is currently standard to personalise treatment decisions. It has been well documented that a broad spectrum of cancers release DNA into peripheral blood (ctDNA). There has been growing interest in use of ctDNA as a non-invasive biomarker to detect the presence of cancer, follow treatment response, gauge prognosis, and monitor for recurrence. Next Generation Sequencing (NGS) has revolutionised genomic exploration and is driving the implementation of precision diagnostics. However, the sensitivity and accuracy of current NGS methods and associated cancer panels are compromised by sequencing errors.This is a fundamental limitation, particularly when aiming to identify rare mutants in genetically heterogeneous mixtures, such as ctDNA. To overcome this limitation, GeneFirst has developed an improved NGS technology with increased sensitivity and accuracy for the concurrent detection of multiple mutations. This project proposes the development of a cost-effective and patient-friendly testing assay for the detection of cancer gene mutations in liquid biopsy, enabling clinically relevant cancer genotyping by non-invasive means.

Awaiting Public Project Summary

Gene mutations have been validated as powerful predictive biomarkers in the management of various cancers; testing for these mutations is currently standard to personalise treatment decisions. It has been well documented that a broad spectrum of cancers release circulating cell-free tumour DNA (ctDNA) into peripheral blood. There has been growing interest in use of ctDNA as a non-invasive biomarker to detect the presence of malignancy, gauge prognosis, follow treatment response or monitor for recurrence. Next Generation Sequencing (NGS) has revolutionised genomic exploration and is driving the implementation of precision diagnostics. However, the sensitivity and accuracy of current NGS methods are limited which is a fundamental limitation particularly when aiming to identify rare mutants in heterogeneous mixtures, such as plasma ctDNA. To overcome these limitations, GeneFirst has developed an improved NGS technology with increased sensitivity and accuracy for the detection of multiple mutations; this makes it suitable for detecting ultra-rare cancer gene mutations in circulating cell-free tumour DNA in blood.

It has been well documented that the release of cell-free DNA into the bloodstream in patients with various types of cancer. There has been growing interest in trying to use such circulating tumour DNA as a non-invasive biomarker to detect the presence of malignancy, follow treatment response, gauge prognosis, or monitor for recurrence. However, current methods have significant limitations. Next Generation Sequencing (NGS) has revolutionised genomic exploration and analysis by making possible simultaneous sequencing of hundreds of billions of base pairs at a fraction of the time and cost of traditional methods. However, the sensitivity of this method is limited by the inherent error rate of the sequencer, as incorrectly read bases might be mistaken for true mutant copies. To overcome this limitation, GeneFirst has developed a method termed Targeted BiDirectional Sequencing technology. This is potentially suitable for detecting rare mutations in circulating cell-free DNA in blood.

Personalised medicine aims to predict in advance which patients are most likely to benefit from, or not respond well to, a particular therapy. However, current methods have significant limitations in terms of both sensitivity and cost. Tumour biopsies, particularly from lung cancers, often provide only a tiny amount of material. Furthermore there may be change in mutations with time, and therefore repeated testing is needed at intervals during treatment, but repeated biopsy is highly undesirable for some tumour types. It has recently been discovered that DNA from tumours leaks into blood and can be detected, if the method is sufficiently sensitive. GeneFirst is developing a new real-time PCR based technology for detection of multiple defined mutations in a single closed-tube with greatly increased sensitivity. This is potentially suitable for detecting mutations using circulating cell-free DNA in blood.

Human papillomavirus (HPV) is one of the most common sexually transmitted infections (STI). Some, but not all, types of HPV can cause cervical cancer (high-risk HPV types, HR-HPV). Since early stage cervical carcinomas are nearly 100% curable, early detection is very important. Accurate molecular diagnosis is needed to inform patient management and follow-up treatment. However, current methods suffer from sub-optimal sensitivity, discrimination and/or complex hybridisation-based procedures. GeneFirst has developed a unique technology (Multiplex Probe Amplification) for sensitive type-specific detection of more than 15 targets (e.g. HR-HPV types) in a single closed tube reaction. In this project, we set out to analyse the clinical performance of this novel HPV molecular diagnostics test to identify patients who have HR-HPV. Such an assay would offer physicians better means to identify women at risk and optimise treatment strategies.

Human papillomavirus (HPV) is one of the most common sexually transmitted infections (STI). Some, but not all types of HPV can cause cervical cancer (high-risk HPV types, HR-HPV). Since early stage cervical carcinomas are nearly 100% curable, early detection is important. Accurate molecular diagnosis is needed to inform patient management and follow-up treatment. However, current methods suffer from sub-optimal sensitivity and complex hybridisation-based procedures. GeneFirst has developed a unique technology (Multiplex Probe Amplification) for sensitive type-specific detection of more than 15 targets (e.g. HR-HPV types) in a single closed tube reaction. In this project, we set out to design, and analyse the market niche for, a robust, accurate, simple and inexpensive HPV molecular diagnostics test to identify patients who have HR-HPV. Such an assay would offer physicians better means to identify women at risk and optimise treatment strategies.