Cancer and the microbiome

Editorial Q&A interview

Cancer - a global health problem and the second leading cause of death worldwide today. The word itself has the ability of sending shivers up and down the spine. A devastating disease that touches the lives of many, from those that have the disease to those who witness first-hand the suffering it causes their loved ones. Over the decades due to the rise in new cancer diagnoses, cancer research has magnified exponentially. Researchers are eager to make headway on tackling this disease and all of its facets head on. A cure for cancer is the aim, but difficult to fulfil, as cancer itself is complex -- a group of many diseases, where genetic, environmental and behavioural factors all have a role to play in its diagnosis. 

Read our interview with the Chief Editor of the soon to launch Nature Cancer, Alexia-Ileana Zaromytidou. Alexia discusses cancer and why it is a field very much close to her heart. Carry on reading to find out more about Alexia, what Nature Cancer plans to offer the cancer research community and Alexia’s thoughts on some of the scientific issues surrounding cancer at the moment.

Alexia-Ileana Zaromytidou

Alexia-Ileana Zaromytidou

Chief Editor, Nature Cancer

nature cancer

Tell us a bit about yourself and your early career path. Which university did you graduate from, what are your research interests and your background? 

 I was born and raised in Greece and after finishing high school I moved to the UK for my undergraduate studies. I received my BSc in Molecular Biology from University College London and stayed in London to complete my PhD at the Cancer Research UK London Research Institute (CRUK LRI), which is now part of the Francis Crick Institute. I then moved to New York City to pursue my postdoctoral work at Memorial Sloan Kettering Cancer Center (MSKCC). After that I joined the Nature Research journals as an associate editor.

 My scientific background is in molecular and cell biology, more specifically on signaling pathways such as MAPK, Rho and TGF-beta/BMP. These signaling cascades control gene expression programs that drive essential cellular functions, including cell proliferation or growth arrest, cell shape and motility and cell fate. When these pathways become deregulated they can lead to cancer. So I would say that cancer biology is my first true love, but my research interests have always been varied. During my years in the lab I always read around topics and developed a great interest in stem cell biology, epigenetics and immunology that only increased during my years as an editor.

Where are you joining Nature Cancer from? What inspired you to become the Chief Editor of Nature Cancer

I joined the Nature Research journals in 2010 as the cancer biology editor of Nature Cell Biology and became the Chief Editor of the journal in 2015. Honing my editorial skills and eventually leading a journal with such a rich and varied scope was an incredible experience. However, cancer research had always been the field closest to my heart and through my editorial work I became even more immersed in this field. So when the opportunity arose to launch a new Nature Research journal that would be entirely dedicated to cancer research, I simply could not resist.

Did you always have a natural appreciation for cancer research, or was there a particular event or travel that sparked your interest here?

Unfortunately, cancer touches the lives of almost everybody, so many of us have a personal interest in understanding this disease and in helping in some way to reduce the suffering it causes. I remember vividly the first time I saw a cancer patient. I was in primary school and seeing this person, a family acquaintance, experiencing the later stages of the disease, was my first brush with the physical and emotional toll of cancer. I still remember thinking “why?” Why is this disease so devastating? This early glimpse of the reality of cancer sparked a first interest, but my true appreciation for cancer research came during my doctoral and postdoctoral training at two very highly respected cancer research institutes. At the CRUK LRI and MSKCC I had the privilege of being immersed in scientific environments seeded with the ground-breaking work of many cancer researchers and clinicians.  

Why launch Nature Cancer now? Why do we need this journal? 

Cancer is the second leading cause of death worldwide. It is a complex biomedical problem with more than 200 different cancer types and genetic, environmental and behavioral factors at play. It is also a huge socioeconomic challenge with certain population groups affected more than others. To address this global health problem cancer research has expanded massively over the last decades encompassing multiple disciplines and creating a need in the community for a truly multidisciplinary journal. We are launching Nature Cancer in response to this community need – Nature Cancer embraces the spectrum of cancer research ranging from basic preclinical to translational and clinical work across the natural, applied and social sciences. We aim to publish research of the highest quality on how cancer forms and progresses, on innovative approaches to diagnose, target and prevent the disease and new ways to understand the societal impact of cancer.

What will Nature Cancer have to offer that will make it stand apart from other journals? 

Nature Cancer will be a truly interdisciplinary journal serving the wider cancer community in a unique way. It will provide cancer researchers with the latest, highest impact original research in the biomedical, physical and social sciences. But it will also offer a unique forum for researchers from different disciplines to synthesize distinct approaches and ideas, to discuss the most recent scientific advances and to contextualize them within the greater framework of cancer research and oncology in society.

Research on cancer has been ongoing for a long time, what breakthroughs have been made recently?

We are lucky to live at a time when biomedical research is thriving. Immunotherapies have been added to the roster of effective treatment options for several cancers and together with targeted therapies are changing the lives of many patients. The advent of deep sequencing, single cell technologies and liquid biopsies has changed the landscape of tumor molecular profiling in the lab and in the clinic. How we use big data to understand the disease and inform therapy options for the individual patient has also been changing rapidly, with machine learning approaches holding the potential to revolutionize data analysis for cancer screening and diagnosis. However, it is important to remember that advances in research do not occur as single, isolated events, but rather arise from a body of knowledge that builds over many years. Targeted therapies and immunotherapies are excellent examples of how understanding the fundamental molecular and cellular mechanisms that lead to tumorigenesis and govern immune responses can result in the development and clinical translation of innovative treatment modalities.  

Cancer and the microbiome is a hot topic at the moment – why so?

The cancer microbiome is a prime example of how multidisciplinary cancer research has become. The field embraced the idea of microenvironmental and systemic influences on cancer long ago, but only in recent years did we gain the ability to study the effect of microbiota in depth, largely based on improved models and technological advancements. Nowadays work on the cancer microbiome spans preclinical animal models and human clinical studies aiming to understand the role of different microorganisms in the development and progression of different cancer types and in the ways of treating them, notably through immunotherapies. This is an area ripe for further research as causal relationships between specific bacteria and cancer phenotypes are still being elucidated and – as seminal preclinical and early clinical work has indicated -- hold the potential of providing new therapeutic or even preventative options. Understanding the mechanisms underpinning the interaction between microbiota and tumors could ultimately permit modulating cancer-promoting microbiomes directly or through dietary and lifestyle interventions, or using therapy-enhancing microbiota as part of treatment strategies.

We still have not found a cure for cancer, but are we closer in accurately diagnosing the difference between potentially lethal and non-lethal cancers?

I think talking about “a cure for cancer” creates the expectation of a single, magic bullet cure that will eradicate all cancers. Should such a cure be found, it would be a thrilling result, but cancer is a group of many diseases that present differently and are subject to extensive intra- and intertumor heterogeneity. This means that improving treatment requires in depth understanding of each tumor type taking into consideration the individual patient. Today we do know of specific cancer types that are intrinsically less aggressive, or less dangerous due to the availability of effective treatment modalities. However, cancer stage at the time of diagnosis remains a key factor in determining prognosis, meaning that early detection and improved screening are extremely important in diagnosing “lethal and non-lethal cancers” as you put it. To that I will add cancer prevention, with cervical cancer being a prominent example – early screening with the Pap test and more recently the addition of the HPV vaccine have been extremely effective making this one of the most preventable cancers.

Immunotherapy has been hailed as a treatment for certain types of cancer, but why is it only some patients respond to it and others do not?

The advent of immunotherapies has generated great excitement in the cancer field and understandably so, given the impressive clinical responses achieved in some cancer types. However, it’s important to remember that rather than a panacea, immunotherapy represents several different types of therapy that include, but are not limited to, immune checkpoint inhibitors, CAR-T cells and cancer vaccines. Like all therapies, some of these are more effective against certain types of cancer than others. Among the many factors that determine the effectiveness of immunotherapy are the tumor genome and epigenome, the tumor microenvironment and tumor immune phenotype, e.g. the degree to which it is infiltrated by lymphocytes, the general immune fitness of the host but also environmental factors, including the microbiome. Elucidating the influence of these and other factors on the effectiveness of immunotherapies and identifying the patients who are more likely to respond, are active areas of preclinical and clinical research that encompass classic tumor immunology and biomarker work but also genomics, transcriptomics, single-cell analyses and systems biology. Other important areas of research pertain to different combinations of distinct immunotherapy regimes, or of immunotherapies and conventional therapies, with hundreds of clinical trials underway. An important point to consider is that many patients who do respond to immunotherapy present with severe adverse effects or develop resistance, and understanding the mechanisms underlying these phenomena is a primary focus for cancer biologists, immunologists and clinicians aiming to improve the efficacy of these treatments.

What do you think are biggest cancer research challenges facing our planet, and how will Nature Cancer address them?

Cancer is a multifaceted, global health problem. On one hand there are many different types of cancer characterized by evolution and heterogeneity, so it is imperative that we understand the molecular and biological underpinnings of the disease to identify and bring new and more effective treatments to the clinic. On the other hand, it is a disease of disparities – some groups of the population bear a disproportionate burden compared to others and it’s essential that we understand the genetic, cultural, socioeconomic, geographic and other factors that underlie these differences. Nature Cancer will address these challenges by publishing the highest quality and most impactful original research and commentary across the breadth of the cancer field, aiming to be a convening platform through which researchers across disciplines can stay informed and be inspired for further work and collaboration.

What are the trends of the future and advances to watch out for within this area?

I hope that we will see advancements in cancer screening, prevention and early detection that will neutralize cancer as a health problem for many individuals. I mentioned previously the development and wider adoption of HPV vaccines as a preventative measure against cervical and other HPV-induced cancers and I hope that we will see more cancer prevention success stories. To that end I am also excited to see how harnessing big data and using artificial intelligence will advance cancer research. At a cancer biology level, I believe that the significant body of work on the interplay of genetic, micro- and macroenvironmental and behavioral factors will continue to build into a more integrated view of how different cancers develop and progress. I also expect exciting developments in the fields of targeted therapies and immunotherapy. Finally, I think that understanding and addressing cancer health disparities will continue to gain prominence to hopefully level the gradient of cancer screening and treatment across the population.

Can you describe what Nature Cancer means to you? What are you hoping to achieve with the journal and how do you see it developing?

Being entrusted with launching a new Nature Research journal in an area as wide-ranging and as important as cancer research is a great privilege and a big responsibility. As cliché as it may sound, Nature Cancer is a labor of love. I don’t think I’ve worked more, or with more enthusiasm before in my life, and as the time to the journal’s launch approaches I’m more and more excited about sharing our vision with our readers. The editorial team of the journal is very passionate about cancer research and science communication, and with Nature Cancer we are aiming to provide a true home for cancer research -- a journal that will address cancer as a global challenge and will inspire further interactions and collaboration through its pages.

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Alexia’s and the editorial team’s passion for cancer is evident. They have clearly set out the goal that Nature Cancer will be the home for cancer research having recognised there is a need for an interdisciplinary journal in the wider cancer community, publishing research from basic preclinical to translational and clinical work across the natural, applied and social sciences. The journal aims to advance cancer research and the ways we understand, diagnose, treat and - one day - cure cancer.

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