Expert Opinion: Dr Nicola McCarthy

Regular readers will have seen our recent interview with Professor Peter Johnson. We’ve cast our net wider this week, interviewing Dr Nicola McCarthy, Chief Editor of the journal Nature Reviews Cancer, to get a different perspective on the progress being made in cancer research.

Nicola worked in a cancer research lab for several years before moving into science publishing.

Cancer Research UK: For you, what were the hot topics in cancer research last year?

Professor Nicola McCarthy

Nicola McCarthy: I think that one of the hottest areas in cancer biology last year relates to the changes that occur in healthy cells that eventually become cancer cells. We now have good methods for accurately determining changes (mutations) that have occurred in the DNA of cancer cells. Projects that aim to identify all of these changes in many different types of cancer are starting to help us understand how cancer is triggered, and why some patients respond better to therapy than others.

This year we’ve also come to a greater appreciation of the changes that can occur in cells that are not related to faults in the DNA itself. Our genes produce proteins that make up our cells and allow them to function, but alterations to these proteins can be influenced not just through changes in the DNA itself [i.e. changes to genes] but also by changes in how much of, or how often, a protein is made. Although these findings add to the complexity of cancer, they also flag potential new avenues for drug development.

Cancer Research UK: What single piece of work or advance recently most excited you?

Nicola McCarthy: This is a difficult question to answer, as there have been many small steps this year that will, in future, help to produce better treatments for cancer. However, as my background is in cancer biology, I think that understanding the control of ‘cell polarity’ – and how this relates to cancer – has been an important piece of work this year.

Cancer Research UK: can you explain a little more about that?

Nicola McCarthy: Most solid cancers, such as breast and prostate cancers, arise in cells that are polarised: they have a ‘top’ and a ‘bottom’, and seem to ‘know’ which way is ‘up’.

Many processes within a cell are controlled by whether they occur at the top or bottom of the cell. Although we’ve known about this for years, we’re now starting to learn exactly how cancer cells can lose this polarisation. And we’ve started to understand precisely how this disrupts cell function. For example, this loss of knowing top from bottom helps cancer cells to divide more often and to move around the body. Several research papers published this year have identified additional proteins involved, and how these are disrupted in cancer cells.

[References are included at the bottom of this post.]

Cancer Research UK: Which recent advance will have the greatest impact on cancer patients?

Nicola McCarthy: There are many that I wanted to include, but in the end I thought I’d highlight something that’s more of a concept than a finding. Apart from a few specific cancers, it is now unlikely that targeting any one altered protein on its own with a specific drug will result in a cure, as cancers contain many altered proteins that all help the cancer cell to survive and grow.

So we’ve now moved to looking at using a combination of drugs with different effects that target several changes within a tumour – hopefully this way we will be able to more effectively rid the body of all cancer cells.

Cancer Research UK: What do you think the next few years of cancer research will bring?

Nicola McCarthy: There’s been a resurgence of interest in understanding the process of how cancer cells move around the body and then grow in organs such as the bone, brain or liver – a process known as ‘metastasis’. Understanding this in detail should help us to develop treatments that specifically prevent this stage of cancer development.

Conversely, the topic of cancer prevention is starting to gain ground. Using drugs to prevent cancer in the general population is difficult, as such drugs would need to have minimal, if any, side effects. But, if we could identify people who are most at risk of developing cancer, we might be able to help them to reduce this risk through encouraging healthy behaviours and prescribing new drugs that help to reduce this risk. Plus, I think we’ll see even more emphasis on research into early diagnosis of cancer and screening programmes targeted to these ‘at risk’ groups.

Cancer Research UK: What do you see as the greatest challenges still to be tackled in cancer?

Nicola McCarthy: We still don’t understand enough about the differences between different people’s cancers – and that limits our ability to treat the disease. We’re all individuals and, although patients will often be diagnosed with breast cancer, for example, there are many different types of breast cancer, and both cancers and patients can respond quite differently to cancer treatments.

We need to be able to start to ‘stratify’ patients so that they are treated with the drugs most likely to be of benefit to them. For this we need to find markers, or biomarkers as they are more commonly called. However, finding reliable markers is proving challenging and requires more painstaking work before we can achieve this goal.

Cancer Research UK: Finally, what inspired you to work in the cancer field?

Nicola McCarthy: Tomorrow’s World and some computer tape! I distinctly remember watching an edition of what I think was the science programme ‘Tomorrow’s World’  in which one of the presenters used some computer tape to represent a cell’s DNA.

Within this DNA, specific yellow strips represented genes that when damaged could result in the generation of cancer. I realised many years later that this report must have been about the discovery of oncogenes (cancer causing genes) in the early 1980s.

During my ‘O’ levels AIDS hit the news and for a while I was convinced that I would study immunology at university, but my fascination with cancer and oncogenes was sealed through my final year undergraduate project which examined a form of cell death, called apoptosis, that provided a new way of understanding how cancers were formed, and I never looked back.

Interview conducted by Olly Childs, Senior Science Communications Officer

References:

Sottocornola, R. et al. (2010) ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development. Dev Cell 19: 126-37. PMID: 20619750

Cong, W. et al. (2010) ASPP2 regulates epithelial cell polarity through the PAR complex. Curr Biol 20: 1408-14. PMID: 20619648

Greschik, N. A. et al. (2010) Lgl, aPKC and crumbs regulate the salvador/warts/hippo pathway through two distinct mechanisms. Curr Biol 20: 573–81. PMID: 20362447

Robinson, B. S., Huang, J., Hong, Y. & Moberg, K. H. Crumbs regulates salvador/warts/hippo signaling in Drosophila via the FERM-domain protein Expanded. Curr Biol 20, 582–90 (2010). PMID: 20362445

Varelas, X. et al. The hippo pathway regulates Wnt/b-catenin signaling. Dev Cell 18, 579–91 (2010). PMID: 20412773