Factors involved in drug resistance in cancer

We have involved several S6 kinases in the regulation of drug resistance in a variety of cancer types, including lung, breast cancer and osteosarcoma. Our current work aims to identify the downstream targets involved in this effect, including translation and mRNA splicing factors (ie. hnRNPA1). Our goal is to propose novel therapeutic targets for cancer treatment and increase our understanding of the molecular mechanisms leading to cancer cell survival. To hear about some of our work on S6 kinase 2 (S6K2) in drug resistance, please see our YouTube video here. To here about our work on RSK1 and 4 kinases regulating drug resistance and metastasis, please watch this video.

Cross-talk between cancer-associated fibroblasts and cancer cells

We study how cancer cells activate fibroblasts and how activated fibroblasts then promote the aggressiveness of tumour cells through feedback loops. We perform proteomics and transcriptomics analysis to identify signalling pathways that mediate this cross-talk with the aim of proposing novel drug combinations that simulataneously target both fibroblasts and cancer cells. As cancer models, we particularly focus on mesothelioma and osteosarcoma, both cancer types where the mesenchymal component in heavily involved in disease progression. To hear about some of our research on mesothelioma, please follow this link.

New therapies for drug-resistant gestational trophoblastic disease

Gestational trophoblastic disease (GTD) is a disease where trophoblastic tumours occur during, or subsequent to, pregnancy. While the cure rate is ~98%, some tumours develop multi-agents resistance and remain uncurable. We are collaborating with researchers at the UK GTD Center to identify new potential therapies for drug resistant GTD. Please, see our video here for an example of our work.

Compounds design/screening/testing for our various target

We are closely working with chemists and structural biologists to design novel compounds targeting our targets of interest. In particular, our collaboration with Prof Tristan Cazenave (PRAIRIE, Paris, France) and Dr Filippo Prischi (King's College London, UK) resulted in the development of a novel AI algorithm which enables the de novo generation of small molecule compounds against bespoke targets. See our YouTube video on this work here.

ASSOCIATED LATEST PUBLISHED WORK 

Mesothelioma/fibroblasts cross-talk

Chrisochoidou, Y 2023 Cell Death and Disease (2023) 14:725 ; https://doi.org/10.1038/s41419-023-06240-x

RSKs in cancer biology

Chrysostomou, S. et al. Science Translational Medicine (2021): Vol. 13, Issue 602, eaba4627; DOI: 10.1126/scitranslmed.aba4627


Drug resistance in choriocarcinoma

Georgiou et al. 2022 Oncogene 41:2540–2554; https://doi.org/10.1038/s41388-022-02251-8

AI in drug discovery

Roucairol, M et al J Chem Inf Model. 2024 Sep 23;64(18):7097-7107. doi: 10.1021/acs.jcim.4c01451