MRC ICASE PARTNERSHIP - Student Project:
Using oncolytic viral therapy to target the tumour microenvironment in chromosomally unstable cancers
Commercial partner Theolytics have identified and developed novel oncolytic viral therapeutics shortly entering the clinical setting. However, the behaviour of these therapeutic agents in a fibroblast-rich, immunosuppressed tumour microenvironment is not currently known and of key interest as these are typically cancers resistant to other immunotherapeutic approaches. In this project, using their lead therapeutic candidates, 2D and 3D co-culture models will be used to characterise the relationship between tumour cell characteristics, fibroblast phenotype and response to oncolytic viral therapy.
MB BCh, Ba(O) (Hons), MRCP (Onc), PhD
Associate Professor, Innate tumour immunology
- Consultant Medical Oncologist, Early Phase Trials
- Understand resistance mechanisms to immune-targeting treatments in cancer;
- Characterise the role of the interaction of chromosomal instability and DNA repair deficiency with immune activation in tumour initiation, progression and response.
- Study tumour microenvironment, fibroblasts and extracellular matrix in chromosomally unstable cancers.
In the Parkes Lab we study intrinsic inflammatory pathways in cancer. These are important immune pathways, present in all cells, that act as emergency response pathways to viral infection. However, in cancer, these pathways can be rewired and hijacked by the tumour to promote growth, invasion and metastasis.
Dr Parkes was the first to describe constitutive innate immune signalling in BRCA1/2 mutant cancers activating cGAS-STING signalling. This work has subsequently led to a clinical trial investigating a biomarker for BRCA1/2 deficiency in breast cancer, as well as interest in the action of STING agonists in BRCA1/2 mutant disease. Her work on ENPP1 and chromosomal instability identified a novel mechanism whereby cGAS-cGAMP-STING signalling can be subverted to result in tumour-mediated immunosuppression. She is an international expert on cGAS-STING signalling in cancer and the impact of this signalling on the tumour microenvironment.
Kathy Chan, Post-Doctoral Researcher
Su Phyu, Post-Doctoral Researcher
Bruno Beernaert, DPhil student
Matt Jackson, DPhil student
Jamie Kwon, DPhil student
Kay Shigemori, DPhil student
Ashley Jackson, MRes student
Subashan Vadibeler, MRes student
Tong Liu, Visiting researcher
GROUP ALUMNI & NEXT DESTINATIONS
Rebecca Sipthorpe (2020-2022), Research technician - Wellcome-funded PhD student at the University of Bristol
Beernaert B. and Parkes EE., (2023), Biochem Soc Trans
Fletcher CE. et al, (2022), Mol Cancer, 21
van Vugt MATM. and Parkes EE., (2022), Trends Cancer, 8, 174 - 189
Parkes EE. et al, (2022), Br J Cancer, 126, 247 - 258
Kwon JTW. et al, (2021), Endocr Relat Cancer, 28, T95 - T107
Phase I, first-in-human trial evaluating BI 1387446 (STING agonist) alone and in combination with ezabenlimab (BI 754091; anti-PD-1) in solid tumors.
Harrington K. et al, (2021), CANCER RESEARCH, 81
Parkes EE. et al, (2021), NPJ Breast Cancer, 7
Yap TA. et al, (2021), Cancer Discov, 11, 1368 - 1397