Prof. McNeish tackles PTEN-mutated ovarian cancers

08 March 2019
Professor Iain McNeish

In this first week of OCAM we’re putting a spotlight on ovarian cancer treatment – particularly the need to create new and better therapies for women through innovative research. We sat down with Professor Iain McNeish, Director of the Ovarian Cancer Research Centre, to find out more about his research on PTEN and the future of ovarian cancer treatment.

Professor Iain McNeish is investigating why ovarian cancer tumours with PTEN mutations grow more rapidly and are less likely to respond to chemotherapy than those without PTEN mutations. By understanding how this mutation works, Prof McNeish hopes that we will be able to treat these tumours and improve ovarian cancer survival rates.

What is PTEN?

PTEN stands for Phosphatase and tensin homolog – a real mouthful! The PTEN gene helps maintain control over cell and tissue growth, ensuring they don’t go out of control.

Why is this important with respect to ovarian cancer?

We know that all cancer cells contain specific mutations (changes) in their DNA, which cause the cells to grow uncontrollably. Around 20 - 25% of ovarian cancers contain mutations in the PTEN gene. We know that tumours with PTEN mutations grow more quickly and are less likely to respond to chemotherapy than those without PTEN mutations. Unfortunately, this means that women with PTEN-mutated ovarian cancer are more likely to die of their disease. The end goal of my research is to uncover how we can help the immune system fight cancers with a PTEN mutations.

Why doesn’t our immune system attack cancer cells, like it does with the cold virus?

The immune system is alerted when cancer starts to grow, and its sends immune cells to attack and kill the tumour’s cells. One group of immune cells, called T cells, are particularly effective at killing tumours in much the same way as they eliminate virus-infected cells. However, cancers have developed mechanisms to avoid being attacked and killed by T cells.

One mechanism involves the cancer hijacking another type of immune cell, called myeloid cells. Myeloid cells are alerted when tumours develop and descend on the tumour to wipe it out. However, the tumours are able to corrupt these myeloid cells so that, instead of attacking the tumour, the myeloid cells start to work for the tumour. They feed the tumour cells, help the tumour to build a better blood supply and, most crucially, stop other immune cells, like T cells, from functioning properly. The cancer therefore uses our own immune cells to shield itself from attack and grow faster. 

What will your research discover?

We wish to understand why tumours with PTEN mutations are more aggressive. To do this, we have grown ovarian cancers with PTEN mutations in the lab. We’re seen that these tumours grow more rapidly and respond less well to chemotherapy.  When we analysed these PTEN-mutated tumours, we found that they contained many myeloid cells.

Crucially, we believe that it is the PTEN mutation in the cancer cells that helps to attract myeloid cells into the tumour. Specifically, we believe that the PTEN mutation makes tumour cells particularly effective at corrupting myeloid cells, and that this corruption occurs much quicker than in other tumours.

How will this affect the immune system?

By understanding how PTEN-mutated ovarian tumours corrupt myeloid cells - specifically the signals they send to attract the myeloid cells they’ll use as their shield - we get one step closer stopping this from happening. This may be possible using drugs that either block the tumour’s signals to myeloid cells or by stopping the effects of the PTEN mutation directly. We believe that this will allow the immune system to function as it should and attack tumour cells.

How will supporters’ money help fund your research?

The funding provided by Ovarian Cancer Action’s amazing supporters will go towards the running of the project. Dr Sarah Spear, a full-time postdoctoral researcher, has been employed on this project and the laboratory consumables – such as glassware and protective clothing, RNA sequencing, and flow cytometry - required for experiments are also being funded.

How will your research help create better ovarian cancer treatments in the future?

At the end of this four-year research project, we hope to have a full understanding of why ovarian cancers with PTEN mutations do so badly. More importantly, we believe that this research will lead directly to a clinical trial in women with PTEN-mutated ovarian cancer using drugs that are already available. If we are correct, these trials could lead to better survival for women with these cancers.

As the UK’s ovarian cancer research charity, we’re proud to have invested over £11.4 million in medical research to date. This coming September we’ll be awarding a significant grant for an immunotherapy or immunology based research project to benefit women with ovarian cancer. The grant will be announced at our HHMT International Forum on Ovarian Cancer. Click here to read more.