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Corrupted cells help tumours resist treatment

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Dr Fernando Calvo is a cancer researcher currently based at the Institute of Biomedicine and Biotechnology of Cantabria in Santander, Spain, where he recently moved to from the Institute of Cancer Research in London. Since 2015, our supporters have funded Dr Calvo’s research looking into how healthy cells in and around a tumour can become corrupted and help tumours develop, grow and spread. The main findings from Dr Calvo’s project have just been published in the journal, Nature Communications, so we caught up with him to find out more about what his team found.

What does your lab focus on?

Our lab is mainly interested in understanding the role of the tumour microenvironment in tumour growth, spread and response to therapy. The tumour microenvironment refers to all the different cell types, healthy and cancerous, that are found in a tumour and which work together to drive tumours.  Our research focuses on a particular population of cells within the tumour microenvironment called the cancer-associated fibroblasts (CAFs). These cells are prominent in most solid tumours and seem to be involved in almost all hallmarks of cancer, suggesting that strategies to target these cells may be a valid alternative for cancer treatment. Before we can get to that stage, we need to understand why, and how, fibroblasts in tumours are “corrupted” and become CAFs. We also need to understand how this corruption causes them to support tumours. These fundamental mechanisms are what my research aims to discover.

What have you been trying to achieve with your funding from Worldwide Cancer Research?

Previous research from our lab suggested that protein found in cells called DKK3 may be important for CAF function. In this project, supported by Worldwide Cancer Research, we aimed to confirm exactly how DKK3 causes CAFs to support tumours and work out how we could potentially use this information to help diagnose or treat patients.

What were the key findings from your newly published research?

In our study, we have found that DKK3 is associated with CAFs that display aggressive behaviour in different types of tumours, including breast, ovarian and colorectal cancers. This means that CAFs that have a higher level of the DKK3 protein seem to drive a more aggressive type of cancer. Importantly, we show that DKK3 is essential for CAFs to promote tumour growth and invasion in several different types of cancer, suggesting that developing treatments to block DKK3 may have strong therapeutic potential. We have now managed to unpick the molecular mechanisms that DKK3 uses to drive aggressive cancers and it is this information that will help us develop novel treatment strategies.

What needs to happen next?

We are very interested in validating our findings in a therapeutic context. In other words, we want to test whether targeting DKK3 function in CAFs improves the efficacy of current cancer therapy, or is able to reduce the emergence of therapeutic resistance. In addition, we are screening drugs to find ones that target DKK3, as well as continuing to explore the novel functions of DKK3 in cancer. Our final goal is to help develop new therapeutic strategies that our clinical colleagues can assess and test in the future.

I strongly believe that therapies directed to CAFs have a strong potential for treating cancer patients. However, contrary to the relative success of other emerging treatments, such as immunotherapy, targeting CAFs is an approach that has not been fully exploited. I hope my research can contribute to the development of these advances in the future.

Do you have a message for all those that support Worldwide Cancer Research?

Firstly, I would like to thank all the people that support Worldwide Cancer Research, as well as patients and their families, for all the time, energy and generosity they give to fundraising, and to helping researchers develop new and more effective ways to treat cancer. This project would have not been possible without the money you have all raised for Worldwide Cancer Research.

As a researcher, I am deeply grateful for organizations such as Worldwide Cancer Research because they support discoveries that are right at the start of the research journey. Their willingness to support the innovative ideas from researchers willing to take intellectual risks is what kick-starts all the fantastic new tests and treatments for cancer. I hope that my research, in combination with other efforts from the scientific community, contributes to improving cancer therapy and a better quality of life for cancer patients, and I thank you all for allowing me to do this.

You can read Dr Calvo's full research article for free at Nature Communications.

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