Institute of Cancer Research Confidence in Concept (ICR CiC)
Lead Research Organisation:
Institute of Cancer Research
Department Name: UNLISTED
Abstract
Institute of Cancer Research Confidence in Concept (ICR CiC)
Technical Summary
Institute of Cancer Research Confidence in Concept (ICR CiC)
People |
ORCID iD |
| Paul Workman (Principal Investigator) |
Publications
Banerji, U
(2023)
Localizing DNA-Damage Response Inhibitors to FRa Expressing Tumors
Caravagna G
(2020)
Subclonal reconstruction of tumors by using machine learning and population genetics.
in Nature genetics
Garancher A
(2020)
Tumor necrosis factor overcomes immune evasion in p53-mutant medulloblastoma.
in Nature neuroscience
George SL
(2020)
Therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma.
in EBioMedicine
George SL
(2020)
Novel therapeutic strategies targeting telomere maintenance mechanisms in high-risk neuroblastoma.
in Journal of experimental & clinical cancer research : CR
King D
(2020)
MYCN expression induces replication stress and sensitivity to PARP inhibition in neuroblastoma.
in Oncotarget
Pearson AD
(2021)
Bromodomain and extra-terminal inhibitors-A consensus prioritisation after the Paediatric Strategy Forum for medicinal product development of epigenetic modifiers in children-ACCELERATE.
in European journal of cancer (Oxford, England : 1990)
Peck B
(2021)
3D Functional Genomics Screens Identify CREBBP as a Targetable Driver in Aggressive Triple-Negative Breast Cancer.
in Cancer research
Poon E
(2020)
Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma.
in The Journal of clinical investigation
| Description | Chair of ESMO 2019 Multidisciplinary session: Is Randomisation of Clinical Trials still the Gold Standard? (ID 31) |
| Geographic Reach | Europe |
| Policy Influence Type | Influenced training of practitioners or researchers |
| URL | https://cslide.ctimeetingtech.com/esmo2019/attendee/confcal/session/calendar/2019-09-28 |
| Description | BCN Catalyst Grant |
| Amount | £403,349 (GBP) |
| Funding ID | 2021JulyPCC1447 |
| Organisation | Breast Cancer Now |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 04/2022 |
| End | 04/2025 |
| Description | Cancer Research UK Cancer Therapeutics Unit 22897 |
| Amount | £50,000 (GBP) |
| Organisation | Institute of Cancer Research UK |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | |
| Description | The Ian Harty Charitable Trust - Pancreatic Cancer Research Fund |
| Amount | £100,000 (GBP) |
| Funding ID | NA |
| Organisation | Ian Harty Charitable Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2021 |
| End | 03/2022 |
| Title | Fluorescence associated cell sorting for immune, tumour, endothelial and cancer associated fibroblast cells |
| Description | This method provides ways to isolate particular cell types including immune, tumour, endothelial and cancer associated fibroblast cells from bulk tissues using antibody based cell sorting. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2017 |
| Provided To Others? | No |
| Impact | This method provided ways to assess immunotherapy treatment effect using mouse models. |
| Title | Immunohistochemistry for immune cells using mouse tissues |
| Description | This method provides opportunities to measure expression of proteins in situ using mouse tissues. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | This provided opportunity to develop methods to detect expression immune cell type markers in mouse tumour tissues. |
| URL | https://cancerdiscovery.aacrjournals.org/content/early/2015/11/17/2159-8290.CD-15-0068 |
| Title | Immunotranscriptomics for Radiotherapy Treated Rectal Cancer Patients |
| Description | We developed new pipelines of bioinformatics methods using transcriptomic data from rectal cancer samples collected before and after radiotherapy. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2018 |
| Provided To Others? | No |
| Impact | This tool helped us to identify immune changes before and after radiotherapy treatment in rectal cancer samples. |
| Title | In vitro immune-cancer co-culture model |
| Description | We have developed co-culture system involving mouse cancer cells/organoids with splenocytes to study immunotherapy. |
| Type Of Material | Model of mechanisms or symptoms - in vitro |
| Year Produced | 2019 |
| Provided To Others? | No |
| Impact | This is helping us to identify personalised immunotherapy possibilities in pancreatic cancer |
| Title | NanoString Assay for mouse modeling |
| Description | This technology allows to measure selected gene expression using NanoString Technologies specifically tailored for pancreatic cancer mouse models. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2016 |
| Provided To Others? | No |
| Impact | This provides opportunity to assess personalised application of immunotherapy in pancreatic cancer. |
| Title | Redefine and validate pancreatic ductal adenocarcinoma (PDA) gene expression subtypes using human tumours and cell lines and cross-organ comparative analysis |
| Description | In previous study (Collisson et al., 2011) we published 3 PDA subtypes namely quasi-mesenchymal (QM-PDA), classical and exocrine-like. In this study, we reclassified the patient PDA samples from publicly available datasets using centroids (specific scores for each gene and subtype) CRC-assigner 786 genes (Sadanandam et al., 2013) into 5 CRCassigner subtypes using Pearson correlation. We used 4 independent datasets (n=284) (i) GSE15417 (Badea et al., 2008), (ii) GSE17891 (Collisson et al., 2011), (iii) TCGA, (4) CCLE (Barretina et al., 2012) to classify pancreatic cancer samples. We performed pre-processing and normalization of these data using different algorithms (methods not described in this summary) before correlation analysis. |
| Type Of Material | Biological samples |
| Provided To Others? | No |
| Impact | We successfully reclassified PDA samples into CRC subtypes as proposed. The proportion of enterocyte subtype is very low in GSE151471 and UCSF data sets, and this probably could be due to low number of samples in these data sets compared to TCGA (n=183 On the other hand, there is a slight decrease in the proportion of goblet-like in TCGA compared to other data sets. This probably due to the reason that there are only subtle differences between goblet-like and enterocyte subtypes, hence, in TCGA data set there is an equal proportion of both the subtypes. The classification of PDA into goblet-like subtype probably indicates the secretory function of pancreatic ductal and acinar cells, similar to mucus secreting goblet cell. Interestingly, proportion of stem-like, TA and inflammatory subtypes are consistent across majority of the data sets. |
| Title | Integration of different gene expression datasets |
| Description | We developed a pipeline of tools to integrate gene expression data from different platform. |
| Type Of Material | Data analysis technique |
| Provided To Others? | No |
| Impact | This led to increase in the number of sample size of clustering gene expression data. |
| Title | Molecular characterisation of pancreatic cancer subtypes using gene expression profiles and deconvolution of immune cells heterogeneity |
| Description | We applied multiple published tools, such as CIBERSORT, ssGSEA, GSEA, to characterise the relative abundance different cell types present in pancreatic cancer patient samples. |
| Type Of Material | Data analysis technique |
| Year Produced | 2017 |
| Provided To Others? | No |
| Impact | This approach allowed us to estimate the relative abundance of different immune cell types in different pancreatic cancer subtypes. Quantifying the prevalence of different immune cells present in a tumour microenvironment can potentially help in identifying patients that are most likely to respond to immunotherapy. |
| Description | Break Induced Replication repair - molecular mechanism and regulation |
| Organisation | Academy of Athens |
| Department | Biomedical Research Foundation Academy of Athens |
| Country | Greece |
| Sector | Charity/Non Profit |
| PI Contribution | We have identified and characterised a novel mechanism that operates at dysfunctional telomeres. Inhibition of this pathway is synthetic lethal with the inhibition of BLM helicase, DNA2 nuclease and Pold3 polymerase. |
| Collaborator Contribution | My collaborator characterised telomeric abnormalities arising upon inhibition of this novel pathway. |
| Impact | Manuscript in preparation |
| Start Year | 2020 |
| Description | Mechanisms of cellular resistance to ATR inhibitors |
| Organisation | Royal Marsden NHS Foundation Trust |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | My laboratory is performing analysis associated with elucidating the mechanism of ATRi resistance in cancer |
| Collaborator Contribution | Identification of genes that confer resistance to ATRi |
| Impact | Manuscript in preparation |
| Start Year | 2019 |
| Description | Mouse cell lines and tumours |
| Organisation | Swiss Federal Institute of Technology in Lausanne (EPFL) |
| Country | Switzerland |
| Sector | Public |
| PI Contribution | We profiled the genetically engineered mouse tumours and cell lines provided by collaborator. |
| Collaborator Contribution | Our collaborator Prof. Doug Hanahan provided genetically engineered mouse tumours and cell lines from pancreatic cancer. |
| Impact | We recently presented at European Society for Medical Oncology (ESMO) Immunology Congress. |
| Start Year | 2016 |
| Description | Pancreatic Ductal Adenocarcinoma patient samples and RNAseq |
| Organisation | University of Verona |
| Department | Applied Research on Cancer (ARC-NET) |
| Country | Italy |
| Sector | Academic/University |
| PI Contribution | We performed RNAseq using patient material obtained from this collaboration. |
| Collaborator Contribution | Prof. Aldo Scarpa from ARC-NET, University of Verona provided pancreatic ductal adenocarcinoma samples. |
| Impact | This project led to RNAseq of patient samples. |
| Start Year | 2012 |
| Description | Transcriptome and sequencing technology partnership |
| Organisation | Mayo Clinic |
| Country | United States |
| Sector | Charity/Non Profit |
| PI Contribution | We have developed computational pipeline for large scale RNAseq data analysis. |
| Collaborator Contribution | Our collaborator Dr. Nagarajan Kannan is collaborating to provide RNAseq technology platform for the research. |
| Impact | We presented a part of the research twice in 2018 and 2019 at European NeuroEndocrine Tumor Society (ENETS) as below. Sadanandam, A.Young, K.Lawlor, R.Patil, Y.Ragulan, C.Luchini, C.Cantu, C.Mansfield, D.Melcher, A.Cunningham, D.Starling, N.Scarpa, A. (2019). Immune Characteristics of Pancreatic Neuroendocrine Tumors According to Grade and Molecular Subtypes, NEUROENDOCRINOLOGY, Vol.108, p.34. Sadanandam, A.Young, K.Nyamundanda, G.Ragulan, C.Lawlor, R.Scarpa, A. (2018). Development of Multiplex Biomarker Assay to Subtype Pancreatic Neuroendocrine Tumors (PanNETs) with Distinct Prognosis and Mutations, NEUROENDOCRINOLOGY, Vol.106, p.164. |
| Start Year | 2017 |
| Title | Folic acid drug conjugate |
| Description | Synthesised folic acid conjugate with PARP inhibitor. Applied for DPFS grant and was unsuccessful. Currently in discussions with two pharmaceutical companies related to the development of ATR inhibitor folate drug conjugates. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2021 |
| Development Status | Actively seeking support |
| Impact | Scientific understanding related to linkers of folic acid within a folate drug conjugate. |
| Title | Folic acid drug conjugate |
| Description | Synthesised folic acid conjugate with microtubule stabilizing agent. Not possible to further develop drug due to lack of efficacy. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2020 |
| Development Status | Closed |
| Impact | Scientific understanding related to linkers of folic acid within a folate drug conjugate. |
| Title | Immunotranscriptomics |
| Description | We have now developed immunotranscriptomics approach for mouse tumours. |
| Type Of Technology | New/Improved Technique/Technology |
| Year Produced | 2020 |
| Impact | We can identify high inflammed tumours before using the organoids from mouse tumours. |
| Description | A talk or presentation at University of Nottingham |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Other audiences |
| Results and Impact | I presented my work at this meeting. |
| Year(s) Of Engagement Activity | 2020 |
| Description | ESMO Immunoncology Congress presentation |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Postdoctoral Fellow from Sadanandam Lab presented the work as a poster at European Society for Medical Oncology (ESMO) Immunoncology Congress in Geneva, Switzerland. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://oncologypro.esmo.org/meeting-resources/esmo-immuno-oncology-congress-2019/a-personalised-app... |
| Description | Interview with Polish radio station |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | A general discussion regarding novel approaches to cancer treatment including "synthetic lethality" based approaches. Polish radio station with a national reach. |
| Year(s) Of Engagement Activity | 2023 |
| Description | Presentation 2 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | 14th Annual Biomarker Congress - Presenter - Anguraj Sadanandam (PI) |
| Year(s) Of Engagement Activity | 2019 |
| Description | Presentation at Oxford - invited talk |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | I was invited to present at Oxford by pancreatic cancer practitioners and researchers. |
| Year(s) Of Engagement Activity | 2020 |