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Early Cancer Institute

 

The Early Cancer Institute funds a number of research projects which investigate new detection technologies.

Using HDGC to build a toolkit to distinguish indolent from consequential early cancer lesions

Principal Investigators: Dr David Wedge, University of Manchester and Prof Rebecca Fitzgerald, University of Cambridge.

Funded by: ACED Pilot Award 2022

Hereditary diffuse gastric cancer (HDGC) provides a unique window into the development of cancer. Driven by germline loss of the CDH1 gene, multiple lesions at different stages of the transformation to malignancy arise in the same individual, representing the ideal model of the indolent to aggressive transformation.

Cambridge has pioneered active surveillance and centralised risk-reducing gastrectomy (RRG), developing a unique biobank of HDGC specimens with extensive follow-up (>12years). Using WGS of LCM material and multiplex immunohistochemistry on normal, indolent and aggressive disease, we will perform a detailed characterisation of the genetic and environmental changes driving transformation to lethal malignancy. We will develop a toolkit for detailed phylogenetic analysis on this data allowing us to map genetic changes to specific phenotypes and identify those which best predict progression to malignancy.

By performing a deep-dive analysis on exemplar individuals with multiple invasive lesions arising on a homogenous genetic background we hope to identify biomarkers that will be broadly applicable to other tumour types. This study will pave the way for a larger project validating identified biomarkers and will develop a toolkit for the analysis of somatic variation in small early lesions and normal tissues in other hereditary and sporadic cancers.

Using a 'Timeline of DCIS progression' to create an improved clinical assay for breast cancer risk

Principal Investigators: Dr Clare Rebbeck and Professor Greg Hannon, University of Cambridge

Funded by: CRUK Early Detection Project Award 2021

We are very excited to receive a CRUK Early Detection Project Award, allowing us to continue our work on ductal carcinoma insitu (DCIS), a considered precursor for invasive breast cancer. DCIS is often treated with aggressive therapy with the intention of reducing the incidence of invasive breast cancer, and ultimately reduce the number of breast cancer associated deaths. The unfortunate reality is that this strategy has not dramatically reduced the incidence of invasive breast cancer.

Furthermore, many have questioned if all DCIS lesions have the same chance to eventually develop into invasive breast cancer. We have made use of the thoughtful tissue donations from a large cohort of women having been diagnosed with DCIS, and have identified potential biomarkers which distinguish patients who developed invasive disease from those that did not. This award will be used to validate these markers in a larger, distinct cohort, an essential step in the goal to provide personalized treatment.

Quantifying immunity to high grade serous ovarian carcinoma for biomarkers for early detection

Principal Investigators: Dr James Brenton, University of Cambridge and Dr Wendy J. Fantl, Stanford University

Funded by: ACED Pilot Award 2021

Dr James Brenton (Cambridge) and Dr Wendy J. Fantl (Stanford) will investigate whether CD9-NK cells can be detected using mass cytometry in the blood samples of women who have been recently diagnosed with ovarian cancer.

Research Abstract
High‐grade serous carcinoma (HGSC) has a very high mortality‐to‐incidence ratio. Early detection of HGSC is infrequent but low‐stage patients have significantly better outcomes. We discovered decidual‐like (dl)‐NK cell subpopulations in chemo‐naïve HGSC tumours using CyTOF mass cytometry. In cancer, dl‐NK cells have pro‐angiogenic and reduced cytotoxic functions. When co‐cultured with HGSC cell lines, NK cells acquired CD9 by trogocytosis and decreased anti‐tumour cytokine production and cytotoxicity. CD9 is highly expressed in HGSC cell lines, primary tumors and fallopian tube cells. CD9‐blocking antibodies restored the killing activity of CD9⁺‐NK‐92 cells. These findings identify a previously unrecognized mechanism of immune suppression in HGSC driven by CD9 trogocytosis. We will test the hypothesis that CD9 trogocytosis by NK cells can be exploited as a biomarker of early disease by determining whether CD9‐NK cells can be detected in peripheral blood from advanced stage HGSC patients using CyTOF analysis screening for other proteins that are trogocytosed by NK cells as potential biomarkers of cancer‐driven immune suppression for CyTOF characterization in patients and use immunofluorescence to enumerate intra‐tumoral dl‐NK cells in matched tumour samples. These studies will establish feasibility for developing a sensitive and specific blood assay for early detection of HGSC.

Exploiting the immune system for early cancer detection

Principal Investigator: Dr Jamie Blundell, University of Cambridge

Funded by: CRUK Early Detection Primer Award 2021

Early stage tumours represent ~0.001% of the body’s volume. For such small tumours, blood-based biomarkers are diluted to levels low enough to fundamentally limit sensitivity. It is therefore crucial to explore biomarkers with the potential to overcome these limitations. The immune system is an exquisitely sensitive and highly specific in-built diagnostic system. Because T-cells recognize and respond to nascent tumours, if T-cell responses could be “read out” in pre-diagnosis blood samples, there is potential to exploit them as a powerful early warning system for cancer. This vision requires analysing TCR repertoires in longitudinal blood samples collected from individuals before they develop an incident cancer.

Two large-scale longitudinal studies, the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and Epidemiological Study of Familial Breast Cancer (EMBRACE), have blood samples collected over decade-long timescales in which thousands of incident cancers arise. These samples will enable us to explore the enormous potential of this idea for early cancer detection but proof of principle for high quality data needs to be established first. Data from this pilot study will be demonstrate whether samples from both UKCTOCS and EMBRACE cohorts provide high quality TCR repertoire data. This data will then justify establishing a larger study where large numbers of pre-diagnosis blood samples are analysed alongside matched incident tumours. This larger study will be able to critically assess blood-based immune-repertoire biomarkers for early cancer detection.

Genomic signatures in cell-free DNA and their role in early detection of cancer

Principal Investigators: Dr Nitzan Rosenfeld, University of Cambridge

Funded by: CRUK Early Detection Primer Award 2021

This primer project funded by the CRUK Early Detection and Diagnosis Research Committee aims to develop machine learning classification models that use whole genome sequencing (WGS) data from cell-free DNA to identify circulating tumour DNA (ctDNA). We will analyse WGS data from plasma samples of cancer patients and combine multiple layers and types of information, with a particular focus on mutation signature patterns: groups of mutations associated with cancer aetiology, risk factors and exposures. In addition to improving ctDNA detection, this project will support training in computational cancer genomics for a researcher with background in physics. Dr Rosenfeld commented, “I am delighted that we will be able through this award to dig deeper into the analysis ctDNA whole genome sequencing. We’ll develop and evaluate methods for analysis of mutation signatures in cell-free DNA to enhance ctDNA detection. It’s a great opportunity to provide training in bioinformatics to address a gap in skills that are increasingly essential for cancer research.”

Establishing optimal methods for cancer early detection using methylation markers (EPITOME): An integrated comparison of three leading-edge platforms for cell-free DNA epigenetic analysis and application to multiple cancer types

Principal Investigators: Dr Charlie Massie, University of Cambridge; Dr Andrew Feber, University College London; Dr Olivier Gevaert, Stanford University; Dr Parag Mallick, Stanford University; Dr Chunxiao Song, University of Oxford (Affiliate)

Funded by: ACED Project Award 2020

Tissue biopsies can be reduced or entirely replaced through the use of minimally invasive tests, however, current methods used in large-scale studies have low efficiency and limited scalability. Due to the lack of data around new methods, they are not utilised for large-scale implementation despite improved sensitivity at a lower cost. Drs Massie, Feber, Gevaert, Mallick and Song plan to compare 3 methods that allow for efficient, non-destructive cell-free DNA methylation analysis. The team will establish new standards, develop SOPs and data analysis workflows that can be utilised in future early detection studies.

Dynamic predictive model for baseline early detection and follow-up re-evaluation of the risk of prostate cancer progression on active surveillance (PROGRESS Prostate)

Principal Investigators: Prof Alexey Zaikin, University College London and Dr Tristan Barrett, University of Cambridge

Funded by: ACED Pilot Award 2020

Using cutting edge modelling methodologies, Prof Zaikin and Dr Barrett aim to develop a predictive model that will be able to provide a baseline estimate as well as continuous re-evaluation of the risk of prostate cancer progression. Their ultimate aim is to produce an open-source clinical decision support tool to be used by both patients and clinicians.

Real-world risk-stratified early detection and diagnosis using linked electronic health records data

Principal Investigators: Prof Georgios Lyratzopoulos, University College London; Prof Antonis Antoniou, University of Cambridge and Prof Ruth Etzioni, Oregon Health and Science University

Funded by: ACED Project Award 2020

Many patients, particularly those with harder-to-suspect cancers, present to GPs with non-specific symptoms. Professors Lyratzopoulos, Antoniou and Etzioni and their collaborators will produce novel algorithms using both state of the art and novel computational approaches to improve the calculation of risk of symptomatic-but-as-yet-undiagnosed cancer. They will analyse longitudinal primary care data, including on prescription history, co-morbidities, diagnostic tests and underlying susceptibility to cancer. This work aims to inform referral guidelines for specialist investigation or assessment, and to improve decision tools supporting doctors in their assessment of cancer risk.

Novel tools for molecular imaging of pancreatic pre-neoplasia

Principal Investigators: Prof Kevin M Brindle, University of Cambridge and Prof H Tom Soh, Stanford University

Funded by: ACED Pilot Award 2020

Pancreatic cancer is often not diagnosed until at an advanced and incurable stage. Most cancers are known to remodel their glycosylation patterns on their surfaces. In this work, Professors Bridle and Soh will develop synthetic reagents that target cell surface glycans for early pancreatic cancer detection, which may also enable potentially curative surgical intervention. The aim is to develop novel molecular imaging tools that can provide key clinical information on early pancreatic cancer development.

Multi-parametric investigation and stratification of indeterminate lung nodules MISIL1

Principal Investigators: Dr Frank McCaughan, University of Cambridge and Dr Phil Crosbie, University of Manchester

Funded by: ACED Pilot Award 2020

A key question in the early detection of lung cancer is whether a molecular biomarker can improve or be complementary to CT scanning algorithms. In this project they will address indeterminate pulmonary nodules in which there is clinical uncertainty whether a scan-detected lung nodule does or does not represent a lung cancer. To date most reported studies have tested one biomarker modality for indeterminate nodules. The hypothesis is to develop a strategy to accurately stratify patients with indeterminate pulmonary nodules into cancer and non-cancer using a multiparametric combination of biomarkers. This would be the first study to apply multiple cutting edge biomarker methodologies to individuals with early stage lung cancer, indeterminate lung cancer and appropriate controls. The results would demonstrate feasibility, direct and refine future efforts and larger-scale clinical trials.

Leverage protease activity in circulating hybrid cells and exosomes for early detection of cancer

Principal Investigators: Dr Jared Fischer, Oregon Health & Science University, Dr Utkan Demirci, Stanford University, Dr Melissa Wong, Oregon Health & Science University, Prof Antonis Antoniou, University of Cambridge

Funded by: ACED Pilot Award 2020

Pancreatic cancer is a leading cause of cancer related deaths partly due to the difficulty in diagnosing the disease early. There are currently no reliable screening tests for pancreatic cancer, highlighting the need to develop early detection biomarkers that are sensitive and specific for pre-cancerous stages, and that can differentiate early cancer from high risk conditions.

In this project they will use a multi-analyte approach combining isolated circulating hybrid cells and exosomes with proteolytic activity assay to develop a test for early stage pancreatic cancer. Proteolytic enzymes have a strong correlation with cancer progression and invasion and we have evidence that early stage pancreatic cancer strongly correlates with high proteolytic activity. By measuring the proteolytic activity assay within specific cells and exosomes, they hope to further enhance the sensitivity and specificity for detecting pancreatic cancer early.

Tiered integrated diagnostics for the early detection of aggressive prostate cancer: The Riskman-TARGET study to develop a novel screening approach for prostate cancer

Principal Investigators: Professor Vincent Gnanapragasam, University of Cambridge, Prof Kenneth Muir, University of Manchester, Dr Artitaya Lophatananon, University of Manchester

Funded by: ACED Pilot Award 2020

To explore the hypothesis that early detection of prostate cancer needs to combine risk factors and account for changes in a man’s prostate physiology and general heath, we propose the Riskman-TARGET concept. This is based on creating a tiered algorithm with forward gateways to the end-point of referral for image guided biopsy. Baseline genomics are used to identify an at-risk cohort for monitoring, interval tests using PSA adjusted for prostate volume and/or biomarkers will be used to monitor and personalised referral thresholds set based on risks of lethal prostate cancer and benefit gains from treatment. If successful, Riskman-TARGET could be used to deliver a risk-stratified, longitudinal screening programme for targeted detection of lethal prostate cancer.

Early Detection of hereditary renal cancer (RCC) [ELECTRIC]

Principal Investigators: Dr Emma Woodward, University of Manchester, Dr Alice Fan, Stanford University, James Whitworth, University of Cambridge and Prof Eamonn Maher, University of Cambridge

Funded by: ACED Pilot Award 2020

Renal cell carcinoma (RCC) is increasing in incidence and frequently presents at an advanced stage which is associated with poor outcomes despite the introduction of costly targeted therapeutic agents. Hereditary renal cell carcinoma (HRCC) provides opportunities for early cancer detection leading to early intervention. In HRCC, regular imaging screening is the current standard of care; however imaging is not always accessible, is time consuming and requires specialist radiological expertise. Tumour-educated platelets are showing promise as a sensitive and discriminatory means of early cancer detection in blood. This project's researchers have identified a platelet transcriptome signature in individuals with early stage sporadic RCC. They will investigate whether this signature is present in individuals with early stage HRCC, which would represent a significant finding providing opportunities to refine and prospectively validate novel tumour biomarker profiles for early detection in a high-risk population.

Organic Opto-Acoustic electronics for early stage detection of cancer

Principal Investigator: Dr Bruno Matarese, Department of Physics

Funded by: Cancer Research UK Cambridge Centre Early Detection Programme Pump Priming Awards 2020

By combining advances in acoustic wave physics and organic optoelectronics, we will open a new route for the electronic detection of pre-leukaemic cells and detailed discrimination from normal blood cells. By using acoustic wave sorting and optical indices in blood samples from selected patients with various grades of blood cancer, we will identify optico-physical properties of cells that correlate with progression to overt malignancy. The integration of in-situ illumination and imaging, made possible by organic optoelectronics, would allow such detection to be achieved within self-contained lab-on-a-chip devices. These would offer cheap, low-power, disposable tools for routine screening of early cancer markers.

Sampling of fallopian tube cells for functional and genotypic characterisation

Principal Investigator: Dr Filipe Correia Martins, Department of Obstetrics & Gynaecology

Funded by: Cancer Research UK Cambridge Centre Early Detection Programme Pump Priming Awards 2020

High-grade serous ovarian cancer (HGSOC) is the commonest form of ovarian cancer, originates in the fallopian tubes (FTs) and is often diagnosed at an advanced stage when options for curative treatment are limited, leading to low survival rates (1‐3).

Our multi‐institutional team is analysing single‐cell molecular profiles from FT samples derived from patients at low and high-risk of developing HGSOC in order to establish if prevalence of somatic copy number alteration (SCNAs) per cell could be used to inform risk stratification. We analysed different cohorts with multiregional sequencing data from HGSOC and defined clonal tumour‐initiating SCNAs. We aim to identify those in FT cells from normal and at‐risk individuals and anticipate they will serve as sensitive markers for early detection of high risk tumour initiating cells.

This proof of concept study will support the aims above by:

  1. Defining what the efficiency of different cell‐sampling methods are;
  2. Establishing the viability of the sampled FT cells and their ability to clonally expand in vitro
  3. Establishing organoid cultures, where clonal expansion of single cells would allow to define specific mutation profiles and how they associate with rate of chromosomal segregation errors or the presence of specific somatic copy number alterations (SCNAs).
Epigenetic enrichment of circulating tumour DNA to enable deep profiling for cancer early detection (EpiEnrich)

Principal Investigator: Team EpiEnrich led by Dr Charlie Massie, CRUK Cambridge Centre Early Detection Programme

Funded by: Cancer Research UK Early Detection Innovation Award (through sensor technology for liquid biopsy sandpit) 2018

A team of 6 PIs from 6 institutions across the UK: Charlie Massie (Cambridge), Paul Millner (Leeds), Francesco Crea (Open University), Tingting Zhu (Oxford), Nick Leslie (Heriot Watt), Pedro Estrela (Bath) are working on the project Epigenetic enrichment of circulating tumour DNA to enable deep profiling for cancer early detection (EpiEnrich). Cell-free tumour DNA (ctDNA) analysis is a highly specific method for non-invasive cancer detection and molecular stratification, but a major challenge for early detection is finding rare events in the context of high background non-tumour DNA. The team aims to deliver a step-change by epigenetic enrichment of ctDNA directly from plasma samples. They will establish new workflows and test the impact of this approach on ctDNA detection rates in early cancers.

Poly-dopamine based nano-senolytics for specific removal of senescent cells

Principal Investigator: Dr Ljiljana Fruk, Department of Chemical Engineering and Biotechnology

Funded by: Cancer Research UK Early Detection Primer Award

This award will fund research work on a biocompatible nanosystem for the removal of senescent cells implicated in cancer formation. They are often considered a first stage of cancer and their detection and removal could prevent cancer development.

Early detection of renal cell carcinoma using DNA methylation markers in urine

Principal Investigators: Dr Charlie Massie & Assistant Professor Oliver Gevaert

Collaborators: Mr Grant Stewart, Academic Urology Group, Dept of Surgery, Cambridge and Dr John Leppert, Dept of Urology, Stanford

Funded by: Cancer Research UK Cambridge Centre and Canary Center at Stanford Early Detection Joint Pump Priming Awards 2018

Renal cell carcinoma is the 7th most common cancer with a high mortality rate. There are currently no early  detection or screening strategies for RCC, or for differentiating between benign and malignant renal masses detected by imaging techniques. Charlie Massie, Group Leader in the Early Detection Programme, will research whether it is possible to detect the early stages of Renal Cell Carcinoma using biomarkers found in urine, initially in patients with renal masses detected by imaging. The hope is that this approach will enable RCC to be accurately detected at a surgically curable stage and will prevent overtreatment of benign lesions. He is collaborating with Oliver Gevaert at the Canary Center to look at specific signals in the DNA cells called methylation.

A multi-modal approach to discover novel blood based biomarkers for early detection of poor prognosis prostate cancer

Principal Investigators: Professor Vincent Gnanapragasam & Assistant Professor Tanya Stoyanova

Collaborators: Dr Charlie Massie, CRUK Cambridge Centre Early Detection Programme and Dr James Brooks, Dept of Urology, Stanford

Funded by: Cancer Research UK Cambridge Centre and Canary Center at Stanford Early Detection Joint Pump Priming Awards 2018

Published paperDiscovery of PTN as a serum-based biomarker of pro-metastatic prostate cancerBr J Cancer (2020). DOI:10.1038/s41416-020-01200-0

Existing blood tests for prostate cancer (PSA) cannot discriminate between clinically non-­‐ significant (indolent) or significant (lethal) disease. Vincent Gnanapragasam, a consultant urologist at Cambridge University Hospitals, is leading an initiative to stratify men diagnosed with prostate cancer according to how aggressive their tumour is. Working with Tanya Stoyanova, a radiology professor at the Canary Center, the project will use data from a number of sources – including tumour DNA found circulating in the blood, protein molecules found in cancer cells and MRI imaging of the tumour – to identify patients with the most aggressive tumours so that they can be treated immediately. Men with slow-growing tumours will also be identified and these patients may not need treatment immediately, but could be monitored closely so that any changes in their tumour can be picked up and acted upon.

Hyperspectral Endoscopy Imaging for Early Detection of Precancerous Lesions in Average Risk and Inflammatory Bowel Disease Patients: Proof of Principle

Principal Investigators: Dr Sarah Bohndiek, (Cambridge), Dr Liana Tsikitis & Sarah Diamond (OHSU)

Funded by: OHSU-CRUK SPARK Award 2018

Published Paper: First experience in clinical application of hyperspectral endoscopy for evaluation of colonic polyps. Biophotonics 2021, e202100078. doi.org/10.1002/jbio.202100078

Dr Sarah Bohndiek and Dr Jonghee Yoon (Cambridge), and Dr Liana Tsikitis (Department of Surgery, OHSU) and Dr Sarah Diamond (OHSU) received a Spark award to collaborate on the project entitled: ‘Hyperspectral endoscopy imaging for early detection of precancerous lesions in average risk and inflammatory bowel disease (IBD) patients’.

The aim of the project was to investigate hyperspectral endoscopy as a visualisation aid for lesions, in particular flat polyps, in the colon that may be missed by the current colonoscopy methods used (high-definition white light endoscopy). In addition, the team examined the use of hyperspectral imaging to improve visualisation of any residual polyp tissue following a polypectomy, which may be a contributing factor to interval colorectal cancer development. The technology will also be investigated as an alternative means of detecting dysplasia in patients with inflammatory bowel disease, a known risk-factor for colorectal cancer.

They designed, built and tested a new compact HySE in a proof-of-concept clinical study and successfully collected spectra from three tissue types in seven patients undergoing routine colonoscopy screening. The acquired spectral data from normal tissue and polyps, both pre- and post- resection, were subjected to quantitative analysis using spectral angle mapping and machine learning, which discriminated the data by tissue type, meriting further investigation of HySE as a clinical tool.

The results of the study can be found in the paper published in the Journal of Biophotonics: First experience in clinical application of hyperspectral endoscopy for evaluation of colonic polyps. Biophotonics 2021, e202100078. doi.org/10.1002/jbio.202100078

Early cancer detection through transcriptomic analysis of host immune cells

Principal Investigators: Dr Robert Rintoul & Professor Tom Soh

Collaborators: Professor Bruce Ponder, Dept of Oncology, Cambridge and Dr Purvesh Khatri, Institute for Transplantation & Immunology, Stanford

Funded by: CRUK Cambridge Centre and Canary Center at Stanford Early Detection Joint Pump Priming Awards 2018

There is currently intense interest in identifying early cancer biomarkers in blood. However, once these biomarkers are shed from tumours, they are immediately diluted by the circulating blood making their concentrations extremely low. Robert Rintoul, a thoracic consultant based at the Royal Papworth Hospital, is exploring a different approach to detect lung cancer at an early stage by studying the immune cells in blood samples to see if there are particular signals that could be used to identify lung cancer early. He is collaborating with H. Tom Soh a professor of radiology at the Canary Center.

Levitating a sponge for the early detection of oesophageal adenocarcinoma

Principal Investigators: Professor Rebecca Fitzgerald & Professor Utkan Demirci

Collaborators: Dr Vinod Vijay Subhash, MRC Cancer Unit and Dr Gozde Durmus, Dept of Biochemistry, Stanford

Funded by: CRUK Cambridge Centre and Canary Center at Stanford Early Detection Joint Pump Priming Awards 2018

Oesophageal adenocarcinoma poses a diagnostic challenge because of its asymptomatic nature until at an advanced stage, and a lack of early detection biomarkers. Rebecca Fitzgerald, is collaborating with Utkan Demirci at the Canary Center where Professor Demirci has developed a new nano-technology using a magnetic field to separate different cell types. They will investigate whether the new technology can be used to separate the mixture of cell types collected from the gullet when patients are given the Cytosponge test developed by Professor Fitzgerald. The Cytosponge TFF3 is a cost effective, minimally invasive method for diagnosing Barrett’s Oesophagus – a common condition that can, in some cases, develop into cancer of the oesophagus. The ability to isolate cells of interest recovered from the Cytosponge will improve the sensitivity of Barrett's assays.

Analysing menstrual fluid at the single cell lever and assaying its suitability for the derivation of epithelial organoids

Principal Investigator: Dr Angela Goncalves, Wellcome Trust Sanger Institute
Co-Investigator: Dr Daniel Gaffney, Cambridge Cardiovascular

Funded by: Cancer Research UK Cambridge Centre Early Detection Programme Gynaecological Cancers Pump Priming Award 2017

The aim of this project is to demonstrate the feasibility and utility of using menstrual fluid collected on day 2 of the menstrual cycle for diagnostics and research. We will characterise cell viability, the cell types present and determine whether MF is a suitable source of cells for the establishment of epithelial cell cultures (epithelial organoids) for in vitro studies.

Point-of-care measurement of PSA subtypes using acoustic sensors for early detection of aggressive prostate cancer

Principal Investigator: Dr Andrew Flewitt, Department of Electrical Engineering
Co-investigator: Professor Vincent Gnanapragasam, Department of Surgery

Funded by: Cancer Research UK Cambridge Centre Early Detection Programme Pump Priming Awards 2016

Published paperSplit resonances for simultaneous detection and control measurements in a single Bulk Acoustic Wave (BAW) sensor, Nanoscale, 2018, DOI: 10.1039/C8NR04665D

The Prostate Specific Antigen (PSA) assay remains the most important first diagnostic test to investigate for the presence of prostate cancer. The current total PSA (tPSA) test however has serious shortcomings and is known to have a low sensitivity and specificity in detecting cancer.

In a recent study from Cambridge only 40% of men referred with an abnormal tPSA were found to have cancer. Conversely, up to 30% of men will harbour prostate cancer despite a normal tPSA. tPSA also has a very poor discrimination in detecting aggressive and clinically significant cancers. Instead many cancers that are detected are indolent and slow growing. There is thus a clear and urgent need for a better point of care test to more accurately detect clinically significant prostate cancer.

There is good evidence that combining tPSA with other PSA subtypes significantly improves detection accuracy. A significant barrier to adopting such a combination test has been the challenges of performing multiplexed assays at the point of care and in real time. This project will address this unmet need in early prostate cancer detection by exploiting a unique collaboration between novel bio-sensing technology (Electronic Engineering) and high-quality sample collections and clinical cohorts (Academic Urology).

Investigation into the accumulation of amyloid as a biomarker for cancer

Principal Investigator: Dr Susana Ros, CRUK Cambridge Institute
Co-Investigator: Professor David Klenerman, Department of Physical Chemistry

Funded by: Cancer Research UK Cambridge Centre Early Detection Programme Pump Priming Awards 2016

Amyloid has long been known to accumulate in neurodegenerative disease. Recent work has demonstrated that amyloid also accumulates in cancer. The amyloid formed offers potentially an entirely new way to detect cancer. Our long-term vision is to study whether measurements of amyloid can be used as a method for early disease detection.

Using holographic capsule technology to develop a test for oesophageal cancer

Principal Investigator: Dr George Gordon, Department of Engineering
Co-Investigator: Professor Tim Wilkinson, Department of Engineering

Funded by: Cancer Research UK Cambridge Centre Early Detection Programme Pump Priming Awards 2016

Published paperRobustness to misalignment of low-cost, compact quantitative phase imaging architectures, OSA Continuum, Vol. 3, Issue 10, pp.2660-2679 (2020).

Half a million cases of oesophageal cancer are diagnosed worldwide each year and the prognosis is poor, with just a 15% survival rate. This is partly because the potential for early detection is limited, which is in turn because large-scale screening is limited by the high operational cost of endoscopy and the limited sensitivity of the current standard, white light endoscopy.

We propose to develop a novel capsule endoscope that is both low-cost and sensitive to variations in reflected optical phase and polarisation caused by microstructural changes in tissue during early malignant transformation. Capsule endoscopes are inherently cheaper to operate than traditional endoscopes because they can be swallowed by the patient without requiring anaesthesia and are manoeuvred by natural peristalsis or a tether. They can therefore be administered in local clinics by a GP or nurse, instead of by a specialist endoscopist in an operating theatre, making large-scale screening feasible.

Design, synthesis and in vitro validation of novel tools for lung cancer diagnosis

Principal Investigator: Dr Daniel Muñoz-Espín, CRUK Cambridge Centre Early Detection Programme

Funded by: Medical Research Council (MRC)

A better understanding of the mechanisms and processes that promote lung cancer is crucial to develop more efficient methods for early diagnosis and to implement more efficient therapeutic interventions. Based on the finding of new molecular targets and the design and development of novel drugs, we aim to inhibit cellular plasticity/stemness as a potential lung cancer therapy. In addition, we are developing new cargo-delivery systems based on nanoparticles that are activated specifically in damaged and/or premalignant cells.