Prof Sara Zanivan - Tumour Microenvironment and Proteomics


Zanivan 2023

Discovery Research

Cancer associated fibroblasts (CAFs) have emerged as a promising therapeutic target in cancer because it is now well established that they actively contribute to tumour pathology. CAFs are a unique cell type in that they are highly secretory, and their secretome dictates the structure of a tumour and influences the behaviour of cancer cells and other cell types.
With our research we want to understand the molecular mechanisms through which CAFs alter the tumour microenvironment (TME) to influence cancer aggressiveness and resistance to therapy.

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High-grade serous ovarian cancer and triple negative breast cancer are the major focus of our research because there are limited therapies against the cancer cells of these tumour types. However, CAFs are highly abundant in these tumours, and our overarching goal is to find ways to target CAFs in combination with other anti-cancer therapies to improve survival of cancer patients.

In the last few years, our work has described unprecedented ways through which CAFs create a TME that supports tumour invasion and metastasis by altering the structure of the extracellular matrix (ECM), and tumour blood vessels' and cancer cells' functions. A major focus of our on-going research is the metabolism of CAFs. We have found that cell metabolism is a major epigenetic regulator of CAF functions and that it can influence the translation of pro-tumorigenic ECM proteins. Our on-going research aims to investigate these aspects further and to understand how targeting specific metabolic pathways affects the composition and structure of the ECM and the immune-TME, and whether it can be exploited to halt cancer progression and improve effectiveness of conventional therapeutic treatments.

Our research is unique in that we mostly work with patient-derived cells that we generate in the lab from tissues that patients kindly donate to research. We also work with pre-clinical models relevant for ovarian and breast cancer. Moreover, because of our established expertise in mass spectrometry (MS)-proteomics, we develop tailored technology to study CAF biology, including their crosstalk signalling with other cell types in co-cultures in vitro and their metabolism in vivo.

Clinical Research

Recently, we have joined the effort to improve early detection of cancer in patients, since detecting cancer at an early stage can dramatically increase opportunities for curative intervention. To tackle this challenge, we are developing novel MS proteomic-based technology for biomarker discovery in body fluids. This research is funded by the CRUK Early Detection and Diagnosis Research scheme.

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This research is funded by the Stand Up to Cancer campaign for Cancer Research UK


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