Supporting the next generation of researchers: Part II

We’re proud to support the next generation of researchers – a commitment which will make a real difference as the cancer sector’s post-pandemic recovery.

During a time of uncertainty due to the pandemic, it’s important that we continue to invest in our current scientific researchers in order to nurture and retain the best talent in Sheffield.

One such individual whose work right here in Sheffield is producing promising results is Brenda Agüero.

Having originally moved to Sheffield from her home in Mexico to study a master’s degree, Brenda secured a PhD position for a project which looked at ways to improve outcomes in ovarian cancer using the drug Avastin.

Avastin is a tumour-starving therapy which can block a form of the protein Vascular Endothelial Growth Factor, aka VEGF.

Normal cells make VEGF, but some cancer cells make too much VEGF. Blocking VEGF may prevent the growth of new blood vessels, including normal blood vessels and blood vessels that feed tumours.

Unlike chemotherapy that attacks the cancer cells, the purpose of Avastin is to block the blood supply that feeds the tumour. This can stop the tumour from growing.

Because Avastin doesn’t work in all patients, it’s important for us to know why this is – to help us better understand which are the most effective forms of treatment for certain cancer patients.

Brenda’s PhD project worked on developing a biomarker to predict which patients would respond to Avastin and which would not, enabling the drug to be offered to patients who will benefit from it.

Brenda’s project successfully managed to:

• Demonstrated the levels of each version of VEGF being produced in an ovarian tumour can predict both survival and Avastin response
• Developed a way to measure these levels in clinical samples, giving a strong potential for it to be used as a clinical test to identify which patients should be given Avastin
• Advanced understanding of the biology of ovarian cancers which respond to Avastin, suggesting that some other drugs could be used in combination with Avastin to improve its effects.

Following the conclusion of her PhD project, Brenda then progressed to her post-doc project, which is currently working to understand how and why resistance can occur in soft tissue sarcoma patients being given the drug Pazopanib, another drug which blocks VEGF receptors.

Some patients benefit hugely from Pazopanib, some don’t respond at all, and those who do respond well frequently go on to develop resistance to the drug. Brenda’s work aims to discover the reasons why resistance to Pazopanib occurs and how it can be overcome, in order to improve patient outcomes and enhance treatment.

Here’s more on her crucial Weston Park-funded work, from Brenda herself.

Tell us more in your own words about your projects and their objectives?

When a tumour begins to grow it needs to form a blood supply to provide itself with the nutrients needed to survive and cause disease. An area of interest for treatment is aimed at targeting and cutting-off the way that the tumour forms its blood supply by targeting specific growth factors that are important in this process.

Unfortunately, not all tumours behave the same way and not all patients respond well to these targeted therapies. My project was focused on understanding the reasons why some patients respond well while others do not, as well as how and why the tumour can become resistant to these treatments.

I began to study this process in ovarian cancer during my PhD and have since moved onto studying this same process in sarcoma.

What would you like the impact of your research to be? How could it benefit people living with cancer?

In essence if we could better understand the way the tumour is able to resist these targeted therapies, we could better identify which patients will and will not respond well to treatment.

This would mean a more personalised treatment strategy and a more efficient service. Sheffield has, over the last few years, had rates of high-grade serous ovarian cancer (the most advanced form of this disease) that have been higher than the national average, and so clearly this would bring about a huge benefit to the local population.