Research & Development Programmes

In house bioanalytical R&D services focused on development of novel diagnostic and therapeutic intervention strategies targeting the cell cycle machinery.

Theranostic patient-centered strategies are often directed against complex and redundant growth signalling networks from surface ligands and receptors through transducers to downstream effector molecules.

However the redundancy of these networks can result in low efficacy of molecularly targeted drugs and constraints on the performance of cancer biomarkers directed at these pathways.

Oncologica’s alternative genetic testing approach is to target the cell cycle machinery, which acts as a convergence point for information transduced through upstream signalling networks and therefore represents an exceptionally attractive diagnostic and therapeutic target.

Research Papers

Utilisation of semiconductor sequencing for the detection of predictive biomarkers in glioblastoma

Utilisation of semiconductor sequencing for the detection of predictive biomarkers in glioblastoma

Published: March 25, 2022 DOI: https://doi.org/10.1371/journal.pone.0245817

Gareth H Williams, Alexander Llewelyn, Robert Thatcher, Keeda-Marie Hardisty, Marco Loddo

SARS-CoV-2 testing and sequencing for international arrivals reveals significant cross border transmission of high risk variants into the United Kingdom

SARS-CoV-2 testing and sequencing for international arrivals reveals significant cross border transmission of high risk variants into the United Kingdom

EClinical Medicine by the Lancet Published:July 14, 2021 DOI: https://doi.org/10.1016/j.eclinm.2021.101021

Gareth H Williams, Alexander Llewelyn, Ruben Brandao, Kaiya Chowdhary,Keeda-Marie Hardisty, Marco Loddo (2021)

Clinical, Radiometabolic and Immunologic Effects of Olaparib in Locally Advanced Triple Negative Breast Cancer: The OLTRE Window of Opportunity Trial

Clinical, Radiometabolic and Immunologic Effects of Olaparib in Locally Advanced Triple Negative Breast Cancer: The OLTRE Window of Opportunity Trial

Front Oncol. 2021; 11: 686776. Published online 2021 Jun 28. doi: https://doi.org/10.3389/fonc.2021.686776

Alfredo Molteni, Alice Bruson, Carla Strina, Carlo Azzini, Daniele Generali, Davide Cerra, Elena Marasco, Elisa Zago, Fabiola Giudici, Francesco Schettini, Gareth H Williams, Giovanni Scambia, Giuseppina Barbieri, Giuseppina Ferrero, Ida Paris, Luciano Xumerle, Manuela Milani, Marco Loddo, Marco Ungari, Maria Chiara Lazzari, Maria Rosa Cappelletti, Marianna Sirico, Nicoletta Ziglioli, Ottavia Bernocchi, Sergio Aguggini, Silvia Paola Corona, Valeria Cervoni

The actionable genomic mutational landscape in solid tumours

The actionable genomic mutational landscape in solid tumours

J Clin Oncol 38: 2020 (suppl; abstr e13642) DOI: https://doi.org/10.1200/JCO.2020.38.15_suppl.e13642

Loddo M, Hardisty KM, Thatcher RP, Haddow TE, Williams GH (2020)

Immunofocus-PD-L1 high throughput quantitative next generation sequencing assay

Immunofocus-PD-L1 high throughput quantitative next generation sequencing assay

J Clin Oncol 38: 2020 (suppl; abstr e13521) DOI: https://doi.org/10.1200/JCO.2020.38.15_suppl.e13521

Williams GH, Thatcher RP, Haddow TE, Hardisty KM, Loddo M (2020)

Druggable fusion gene landscape in solid tumors

Druggable fusion gene landscape in solid tumors

J Clin Oncol 38: 2020 (suppl; abstr e13517) DOI: https://doi.org/10.1200/JCO.2020.38.15_suppl.e13517

Williams GH, Thatcher RP, Nevado B, Haddow TE, Hardisty KM, Loddo M (2020)

Inter-observer Reliability of Programmed Cell Death Ligand-1 Scoring Using the VENTANA PD-L1 (SP263) Assay in Non-Small Cell Lung Cancer

Inter-observer Reliability of Programmed Cell Death Ligand-1 Scoring Using the VENTANA PD-L1 (SP263) Assay in Non-Small Cell Lung Cancer

J Thorac Oncol. 2019 Nov 25. pii: S1556-0864(19)33664-0. doi: https://doi.org/10.1016/j.jtho.2019.11.010.

Williams GH, Nicholson AG, Snead DRJ, Thunnissen E, Lantuejoul S, Cane P, Kerr KM, Loddo M, Scott MLJ, Scorer PW, Barker C. (2019)

Mapping the binding sites of antibodies utilized in programmed cell death ligand-1 predictive immunohistochemical assays for use with immuno-oncology therapies

Mapping the binding sites of antibodies utilized in programmed cell death ligand-1 predictive immunohistochemical assays for use with immuno-oncology therapies

Mod Pathol. 2019 Sep 26. doi: https://doi.org/10.1038/s41379-019-0372-z. [Epub ahead of print] Erratum in: Mod Pathol. 2019 Oct

Lawson NL, Dix CI, Scorer PW, Stubbs CJ, Wong E, Hutchinson L, McCall EJ, Schimpl M, DeVries E, Walker J, Williams GH, Hunt J, Barker C. (2019)

Immunophenotypic analysis of cell cycle status in acute myeloid leukaemia: relationship to cytogenetics, genotype and clinical outcome

Immunophenotypic analysis of cell cycle status in acute myeloid leukaemia: relationship to cytogenetics, genotype and clinical outcome

Br J Haematol. 2018 May;181(4):486-494. doi: https://doi.org/10.1111/bjh.15211. Epub 2018 Apr 20.

Sellar RS, Gale RE, Khwaja A, Garbowski M, Loddo M, Stoeber K, Williams GH, Linch DC

Relevance of deep learning to facilitate the diagnosis of HER2 status in breast cancer.

Relevance of deep learning to facilitate the diagnosis of HER2 status in breast cancer.

Nature – Scientific Reports, April 2017, 7, 45938 DOI: https://doi.org/10.1038/srep45938

Michel E. Vandenberghe, Marietta L. J. Scott, Paul W. Scorer et al (2017)

Integration of next-generation sequencing in clinical diagnostic molecular pathology laboratories for analysis of solid tumours; an expert opinion on behalf of IQN Path ASBL

Integration of next-generation sequencing in clinical diagnostic molecular pathology laboratories for analysis of solid tumours; an expert opinion on behalf of IQN Path ASBL

Virchows Arch (2016). doi: https://doi.org/10.1007/s00428-016-2025-7.

Zandra C Deans, Jose Luis Costa, Ian Cree, Els Dequeker, Anders Edsjö, Shirley Henderson, Michael Hummel, Marjolijn JL Ligtenberg, Marco Loddo, Jose Carlos Machado, Antonio Marchetti, Katherine Marquis, Joanne Mason, Nicola Normanno, Etienne Rouleau, Ed Schuuring, Keeda-Marie Snelson, Erik Thunnissen, Bastiaan Tops, Gareth Williams, Han van Krieken, Jacqueline A Hall, On behalf of IQN Path ASBL

p53 controls CDC7 levels to reinforce G1 cell cycle arrest upon genotoxic stress

p53 controls CDC7 levels to reinforce G1 cell cycle arrest upon genotoxic stress

Cell Cycle. 2016 Sep 9:0 DOI: https://doi.org/10.1080/15384101.2016.1231281

Tudzarova S, Mulholland P, Dey A, Stoeber K, Okorokov AL, Williams GH

Cell cycle status in AML blast cells from peripheral blood, bone marrow aspirates and trephines and implications for biological studies and treatment

Cell cycle status in AML blast cells from peripheral blood, bone marrow aspirates and trephines and implications for biological studies and treatment

Br J Haematol. 2016 Apr 8. doi: https://doi.org/10.1111/bjh.14055

Sellar RS, Fraser L, Khwaja A, Gale RE, Marafioti T, Akarca A, Hubank M, Brooks T, Stoeber K,Williams G, Linch DC

Cdc7 is a potent anti-cancer target in pancreatic cancer due to abrogation of the DNA origin activation checkpoint

Cdc7 is a potent anti-cancer target in pancreatic cancer due to abrogation of the DNA origin activation checkpoint

Oncotarget. 2016 Feb 23. doi: https://doi.org/10.18632/oncotarget.7611.

Huggett MT, Tudzarova S, Proctor I, Loddo M, Keane MG, Stoeber K, Williams GH, Pereira SP.

Do Cell-Cycle Phase-Specific Markers Predict Disease Grade, Stage, and Outcome in Cervical Carcinoma?

Do Cell-Cycle Phase-Specific Markers Predict Disease Grade, Stage, and Outcome in Cervical Carcinoma?

Int J Gynecol Cancer. 2015 Jul;25(6):1066-72.

Kuku S, Proctor I, Loddo M, Kadalayil L, KhoshZaban M, Ledermann J, McCormack M.

Pregnancy-associated plasma protein A regulates mitosis and is epigenetically silenced in breast cancer

Pregnancy-associated plasma protein A regulates mitosis and is epigenetically silenced in breast cancer

J Pathol. 2014 Aug;233(4):344-56.

Loddo M, Andryszkiewicz J, Rodriguez-Acebes S, Stoeber K, Jones A, Dafou D, Apostolidou S, Wollenschlaeger A, Widschwendter M, Sainsbury R, Tudzarova S, Williams GH.

Subcellular proteomics reveals a role for nucleo-cytoplasmic trafficking at the DNA replication origin activation checkpoint

Subcellular proteomics reveals a role for nucleo-cytoplasmic trafficking at the DNA replication origin activation checkpoint

J Proteome Res. 2013 Mar 1;12(3):1436-53

Mulvey CM, Tudzarova S, Crawford M, Williams GH, Stoeber K, Godovac-Zimmermann J

Bladder cancer diagnosis and identification of clinically significant disease by combined urinary detection of Mcm5 and nuclear matrix protein 22

Bladder cancer diagnosis and identification of clinically significant disease by combined urinary detection of Mcm5 and nuclear matrix protein 22

PLoS One. 2012;7(7):e40305

Kelly JD, Dudderidge TJ, Wollenschlaeger A, Okoturo O, Burling K, Tulloch F, Halsall I, Prevost T, Prevost AT, Vasconcelos JC, Robson W, Leung HY, Vasdev N, Pickard RS, Williams GH, Stoeber K.

The cell cycle and cancer

The cell cycle and cancer

J Pathol. 2012 Jan;226(2):352-64.

Williams GH, Stoeber K.

Exploring the interaction between siRNA and the SMoC biomolecule transporters: implications for small molecule-mediated delivery of siRNA

Exploring the interaction between siRNA and the SMoC biomolecule transporters: implications for small molecule-mediated delivery of siRNA

Chem Biol Drug Des. 2012 Jan;79(1):9-21.

Gooding M, Tudzarova S, Worthington RJ, Kingsbury SR, Rebstock AS, Dube H, Simone MI, Visintin C, Lagos D, Quesada JM, Laman H, Boshoff C, Williams GH, Stoeber K, Selwood DL.

Molecular architecture of the DNA replication origin activation checkpoint

Molecular architecture of the DNA replication origin activation checkpoint

EMBO J. 2010 Oct 6;29(19):3381-94.

Tudzarova S, Trotter MW, Wollenschlaeger A, Mulvey C, Godovac-Zimmermann J, Williams GH, Stoeber K.

Two ubiquitin ligases, APC/C-Cdh1 and SKP1-CUL1-F (SCF)-beta-TrCP, sequentially regulate glycolysis during the cell cycle

Two ubiquitin ligases, APC/C-Cdh1 and SKP1-CUL1-F (SCF)-beta-TrCP, sequentially regulate glycolysis during the cell cycle

Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5278-83.

Tudzarova S, Colombo SL, Stoeber K, Carcamo S, Williams GH, Moncada S.

Targeting DNA replication before it starts: Cdc7 as a therapeutic target in p53-mutant breast cancers

Targeting DNA replication before it starts: Cdc7 as a therapeutic target in p53-mutant breast cancers

Am J Pathol. 2010 Oct;177(4):2034-45.

Rodriguez-Acebes S, Proctor I, Loddo M, Wollenschlaeger A, Rashid M, Falzon M, Prevost AT, Sainsbury R, Stoeber K, Williams GH.

Diagnosis of prostate cancer by detection of minichromosome maintenance 5 protein in urine sediments

Diagnosis of prostate cancer by detection of minichromosome maintenance 5 protein in urine sediments

Br J Cancer. 2010 Aug 24;103(5):701-7.

Dudderidge TJ, Kelly JD, Wollenschlaeger A, Okoturo O, Prevost T, Robson W, Leung HY, Williams GH, Stoeber K.

DNA replication licensing factors and aneuploidy are linked to tumor cell cycle state and clinical outcome in penile carcinoma

DNA replication licensing factors and aneuploidy are linked to tumor cell cycle state and clinical outcome in penile carcinoma

Clin Cancer Res. 2009 Dec 1;15(23):7335-44.

Kayes OJ, Loddo M, Patel N, Patel P, Minhas S, Ambler G, Freeman A, Wollenschlaeger A, Ralph DJ, Stoeber K, Williams GH.

Cdc7 kinase is a predictor of survival and a novel therapeutic target in epithelial ovarian carcinoma

Cdc7 kinase is a predictor of survival and a novel therapeutic target in epithelial ovarian carcinoma

Clin Cancer Res. 2009 Apr 1;15(7):2417-25.

Kulkarni AA, Kingsbury SR, Tudzarova S, Hong HK, Loddo M, Rashid M, Rodriguez-Acebes S, Prevost AT, Ledermann JA, Stoeber K, Williams GH.

Phospho-STAT5 and phospho-Akt expression in chronic myeloproliferative neoplasms

Phospho-STAT5 and phospho-Akt expression in chronic myeloproliferative neoplasms

British Journal of Haematology, 2009, Vol. 147: p495-506 DOI: https://doi.org/10.1111/j.1365-2141.2009.07870.x

L. F. Grimwade, L. Happerfield, C. Tristram Lisa Happerfield et al (2009)

Cell-cycle-phase progression analysis identifies unique phenotypes of major prognostic and predictive significance in breast cancer

Cell-cycle-phase progression analysis identifies unique phenotypes of major prognostic and predictive significance in breast cancer

Br J Cancer. 2009 Mar 24;100(6):959-70.

Loddo M, Kingsbury SR, Rashid M, Proctor I, Holt C, Young J, El-Sheikh S, Falzon M, Eward KL, Prevost T, Sainsbury R, Stoeber K, Williams GH.

Modular assembly using sequential palladium coupling gives easy access to the SMoC class of cellular transporters

Modular assembly using sequential palladium coupling gives easy access to the SMoC class of cellular transporters

Chembiochem. 2008 Jul 21;9(11):1787-96.

Rebstock AS, Visintin C, Leo E, Garcia Posada C, Kingsbury SR, Williams GH, Stoeber K, Selwood DL.

Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in bile aspirates

Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in bile aspirates

Br J Cancer. 2008 May 6;98(9):1548-54.

Ayaru L, Stoeber K, Webster GJ, Hatfield AR, Wollenschlaeger A, Okoturo O, Rashid M, Williams G, Pereira SP.

Cell cycle markers in clinical oncology

Cell cycle markers in clinical oncology

Curr Opin Cell Biol. 2007 Dec;19(6):672-9.

Williams GH, Stoeber K.

DNA replication licensing factors and aurora kinases are linked to aneuploidy and clinical outcome in epithelial ovarian carcinoma.

DNA replication licensing factors and aurora kinases are linked to aneuploidy and clinical outcome in epithelial ovarian carcinoma.

Clin Cancer Res. 2007 Oct 15;13(20):6153-61.

Kulkarni AA, Loddo M, Leo E, Rashid M, Eward KL, Fanshawe TR, Butcher J, Frost A, Ledermann JA, Williams GH, Stoeber K.

Hexameric ring structure of human MCM10 DNA replication factor

Hexameric ring structure of human MCM10 DNA replication factor

EMBO Rep. 2007 Oct;8(10):925-30.

Okorokov AL, Waugh A, Hodgkinson J, Murthy A, Hong HK, Leo E, Sherman MB, Stoeber K, Orlova EV, Williams GH.

Mitogenic growth signalling, DNA replication licensing, and survival are linked in prostate cancer

Mitogenic growth signalling, DNA replication licensing, and survival are linked in prostate cancer

Br J Cancer. 2007 May 7;96(9):1384-93.

Dudderidge TJ, McCracken SR, Loddo M, Fanshawe TR, Kelly JD, Neal DE, Leung HY, Williams GH, Stoeber K.

DNA replication licensing, and survival are linked in prostate cancer

DNA replication licensing, and survival are linked in prostate cancer

Br J Cancer. 2007 May 7;96(9):1384-93.

Dudderidge TJ, McCracken SR, Loddo M, Fanshawe TR, Kelly JD, Neal DE, Leung HY, Williams GH, Stoeber K.

Small-molecule mimics of an alpha-helix for efficient transport of proteins into cells

Small-molecule mimics of an alpha-helix for efficient transport of proteins into cells

Nat Methods. 2007 Feb;4(2):153-9.

Okuyama M, Laman H, Kingsbury SR, Visintin C, Leo E, Eward KL, Stoeber K, Boshoff C, Williams GH, Selwood DL.

Novel markers of cell kinetics to evaluate progression from cirrhosis to hepatocellular carcinoma

Novel markers of cell kinetics to evaluate progression from cirrhosis to hepatocellular carcinoma

Liver Int. 2006 May;26(4):424-32.

Quaglia A, McStay M, Stoeber K, Loddo M, Caplin M, Fanshawe T, Williams G, Dhillon A.

DNA replication licensing and cell cycle kinetics of normal and neoplastic breast

DNA replication licensing and cell cycle kinetics of normal and neoplastic breast

Br J Cancer. 2005 Nov 28;93(11):1295-300.

Shetty A, Loddo M, Fanshawe T, Prevost AT, Sainsbury R, Williams GH, Stoeber K.

Repression of DNA replication licensing in quiescence is independent of geminin and may define the cell cycle state of progenitor cells

Repression of DNA replication licensing in quiescence is independent of geminin and may define the cell cycle state of progenitor cells

Exp Cell Res. 2005 Sep 10;309(1):56-67.

Kingsbury SR, Loddo M, Fanshawe T, Obermann EC, Prevost AT, Stoeber K, Williams GH.

DNA replication licensing in peripheral B-cell lymphoma

DNA replication licensing in peripheral B-cell lymphoma

J Pathol. 2005 Feb;205(3):318-28.

Obermann EC, Eward KL, Dogan A, Paul EA, Loddo M, Munson P, Williams GH, Stoeber K.

Mcm2, Geminin, and KI67 define proliferative state and are prognostic markers in renal cell carcinoma

Mcm2, Geminin, and KI67 define proliferative state and are prognostic markers in renal cell carcinoma

Clin Cancer Res. 2005 Apr 1;11(7):2510-7.

Dudderidge TJ, Stoeber K, Loddo M, Atkinson G, Fanshawe T, Griffiths DF, Williams GH.

DNA replication licensing in somatic and germ cells

DNA replication licensing in somatic and germ cells

J Cell Sci. 2004 Nov 15;117(Pt 24):5875-86.

Eward KL, Obermann EC, Shreeram S, Loddo M, Fanshawe T, Williams C, Jung HI, Prevost AT, Blow JJ, Stoeber K, Williams GH.