Science Issue – Pharmacogenomics: Getting Personal in Immuno-oncology

15b-graphicNewsNot all patients have the same genetic make up – it is estimated that differences between individuals account for 20-95% of variability in drug dispositions and effects. This means that the benefits of a single drug may only be evident in a subset of patients, rather than being uniform across the whole population.

Pharmacogenomics is a field of science that uses information about an individual’s genes, proteins and environment to predict an individual’s response to certain drugs, and create a personalized treatment.

Finding unique patterns in an individual’s genetic makeup through “biomarker” analysis, allows the identification of groups of patients who have the same molecular variation of the disease, and thus, may benefit from a certain drug or combinations of drugs.  Identification of the right group of drugs for a patient leads to 1) a higher probability of successful treatment, 2) reduces the probability of negative side effects.

For example, in breast cancer, there are a number of gene expression signatures that have been developed that can be used to estimate prognosis for an individual patient based on assessment of the tumour. In patients who have a form known as “HER-2+ breast cancer”, overexpression of the HER-2 gene leads to a higher than normal expression of the HER-2 receptor in breast cancer cells. The drug, trastuzumab, was been developed specifically to interfere with the receptor. A number of next-generation drug combinations have recently become available, allowing treatments to be further personalised with a greater chance of successful treatment.

More recently, pharmacogenomics has been applied to an exciting new field known as immuno-oncology (I/O). These treatments use an individual’s own immune system to help fight cancer through use of a single I/O drug or combinations of drugs. Normally, white blood cells known as “T-cells” in an individual’s immune system recognize cancer cells as foreign and attack and kill the problem cells. Certain types of cancer exhibit molecules on their surface, known as PD-L1. Interaction with the T-cell surface molecule (known as PD-1) protects the cancer cell from being attacked by T-cells. However, this attack can be reactivated by drugs that block the PD-L1/ PD-1 interaction. To date, single agent anti-PD-1 / PD-L1 has demonstrated survival benefit in five cancer types – bringing hope to many patients who previously had very few treatment options.

The next wave of innovation is to develop effective I/O combination treatments to address patients who do not benefit from monotherapies, and in this regard, it is critical to co-develop a biomarker that will guide treatment selection. AstraZeneca, Bristol-Myers Squibb, Merck and Roche are key players in the Pharmaceutical industry who are leading I/O combination therapy development. The scientific and medical communities are excited to see data in the coming years, with new presentations at the cancer conference, American Society Of Clinical Oncology, in June 2017.

As the options for personalized medicines expand, biomarkers will also play an important role beyond the lab and the clinic.

They will be vital in ensuring patients receive the most effective combination of treatments at a time when healthcare budgets are under significant pressure.

Eleanor Fung
Director – Global Product & Portfolio Strategy at AstraZeneca

Further reading:
Molecular Oncology 2012, 6: 140
Semin Oncol. 2016 43:501.
J Immunother Cancer. 2016; 4:48
Lancet Oncol. 2016;17:e347-62

Career Path: Mineral Sciences to People Management – applying scientific approaches in unlikely ways

Career15a-clare-and-koalaOver the 10 years since I began studying Natural Sciences at Murray Edwards, I have come to realise that although I don’t use the scientific knowledge that I gained during my degree (at all!), I do use the scientific skills and approach to learning that I gained (a lot!).

While at Murray Edwards I spent a lot of my time and energy doing people-focussed things alongside my studies, within and beyond the college. It was this experience that helped me realise that combining my scientific approach to work and problem solving, but also involving people and teams, was where I wanted to focus my energies. This has turned into a career in Human Resources focussing on Organisational Development. I work with people across organisations to understand underlying business issues, and support people and teams to get the most out of their work and deliver the best possible results. This means managing change projects to make work more efficient and effective, and designing and delivering training, resources and team events.

I enjoy my work because it requires a combination of big thinking and detail focus. On one hand I have to understand an organisation’s strategy at a high level and the wide range of factors that may be affecting an organisation’s performance, internally and externally (like understanding overarching scientific theory and models). On the other hand, I look at specific and detailed data, to investigate particular teams’ ways of working more closely, and to identify underlying issues and problems (like gathering and analysing data in scientific research).

I have come to realise that I use scientific approaches in my work more often than you might expect:

  • At the heart of working in Organisational Development is having an understanding of relevant theories and models – these might be about learning and development, motivation and engagement, or change management. I find out what knowledge has already been developed and keep up to date with what research has already been done. Most importantly I have to combine these models and theories into my own understanding of the field.
  • I consider business problems as interesting questions – “why is this team getting lower customer service feedback than the rest of the department?” or “if we change a particular system, how will that affect ways of working across the organisation?”
  • By applying existing knowledge to the question at hand, I can identify potential answers and come up with a hypothesis – “people in the team are not as engaged with their work, which means they aren’t giving as good customer service”
  • I test my hypotheses by gathering and analysing data – recent employee engagement surveys, feedback from teams and from customers, or performance data. This can mean discovering that the answer to the question is not what I expected. I must be open to changing my thinking based on the evidence I observe.
  • Working with managers to improve ways of working, I communicate relevant theories and describe how it applies to their context in an understandable way, and I have to share and explain the findings from my analysis.

Having studied sciences I am able think critically about what I see and what I know, I can use what I observe to challenge my thinking, and I can put my work into much bigger context. I am excited about continuing to apply the skills I learned in my science degree to all my jobs in the future – I have found that these skills are incredibly transferable between organisations (I have worked in charities, a museum and in food retail), as well as countries (I have recently moved from London to Melbourne, Australia!). I would encourage everyone to consider study sciences as it opens up so many possibilities – it absolutely doesn’t mean you will only be able to do jobs labelled as “scientist”, as you can take a scientific approach to anything you do.

Clare Tyson

School Winner: Humans and Perception

emily-hockham-qegs-horncastle14c-emily-horncastle-croppedEssentially everyone has their own reality. Everyone has their own little world with thousands of things different to the person stood next to them.  Say for example there were fifty things going on at every given moment around every person on the planet, and we observe maybe 30 of these at every given moment; any slight change to the world around us. Well those thirty things that you witness and subconsciously notice are going to be different to the thirty I witness.

Perception essentially is the way in which everyone interprets different signals in order to react. For example, you perceive danger to be occurring and your nervous system would be working in order to get you out of that situation. Although everyone’s perception is different and therefore we all make decisions based on different thought processes changing how we act in different situations- and this obviously makes us all so wonderfully different. So why are there certain things that we try and attempt to all perceive to be the same?

Colours delve into the depth of this too. Your green is different to my green, your red is different to my red and so on. To combat this, we have somehow come up with a standard colour that everyone is apparently seeing to categorise the parts of the visible light spectrum that are reflected by different surfaces.

On a basic level, we need sensory perception in order to be able to stay alive; even this differs. In the past some psychologists thought that sensory impressions for example seeing something and perceptions of seeing something were the same – although this isn’t accurate as everyone is different. A light moving through darkness might be seen as a light simply gliding along however it may be perceived as a series of lights being turned on and off in succession.

Every living organism constantly receives multiple sensory impressions, but perceives relatively few objects and events at a given time. Obviously if we perceived everything going on around us we would face almost an overload! So we are trained to perceive things that are opposite to the rest of the items going on as a safety feature, also perception is based on personality, motives, interests, expectations.

Following this conclusion why are there certain things we perceive as wrong? Some people perceive different cultural and social activities to be wrong, in a similar way they perceive red being the colour red. It sounds trivial in this way although it brings to light the idea that if we simply put away all perception thoughts that weren’t necessary, such as sensing danger, then the world would be a much easier place to live in.

Does it matter that we all see colours differently?

Does it matter that some people have different views on the world and how they want to live? Perception should be used to our advantage, not to segregate certain things. People should be metaphorically open to all the colours of the universe.

Emily Hockham
Queen Elizabeth’s Grammar School, Horncastle

“I am currently in Year 12 studying Chemistry, Physics, Biology and Maths A levels. In the future I would like to train to be a surgeon.”

Science at Cambridge: Neuroscience and moody teenagers

14d-megan-hutchings-photo-3UniversityI studied Natural Sciences at Murray Edwards College, specialising in Neuroscience in my final year. I had been interested in Neuroscience ever since completing my Extended Project in high school. In my project I looked into the debate about whether adolescent behaviour was more influenced by genetics or by the environment. Although honestly I was just searching for an excuse to be a moody teenager and not be blamed for it! After my initial interest was sparked I became more and more interested in Neuroscience. I find this subject fascinating as I find studying Neuroscience a way of trying to understand how humans work at the most fundamental level.

I particularly enjoyed studying a modular course at Cambridge as it allowed me to study the aspects of my subject I find most interesting, I particularly enjoyed the fact I was able to take modules on neural networks as well as a psychology module on memory.

My studies never ceased to fascinate me and made me realise just how amazing our brain and by extension we as humans are. There was a continual realisation of how seemingly simple processes are actually much more complex than they appear on the surface. For example, vision seems fairly straightforward, but you can find people who are ‘blind’ but can still tell you where objects are or how they are orientated, even though they cannot ‘see’ them. Or that memories are not fixed and immutable and can be updated or altered. Even that we have different types of memories! All of this I found fascinating and it made me appreciate my brain and my body so much more when I could understand a slightly larger proportion of what it was doing for me on a daily basis.

This in part is why I would encourage young women today to pursue science as a subject; the ability to understand more about the world around you or yourself can only lead to a greater appreciation of how wondrous these things truly are.

Megan Hutchings