One of the great things about working at Karolinska Institutet is that its fame and medical specialisation ensure ever-present opportunities to hear great talks by major advancers in all fields of medical science. A little while ago I was able to attend a talk by one of the first names a young eager cancer researcher will learn in their introduction to the field, and many many times over; Douglas Hanahan (absent, his co-author in fame, Robert Weinberg.)
To understand their contribution we have to rewind a little in time. In the last 75-100 years the molecular and cell biology revolution has exploded, fuelled by our technological advances. Very quickly, the amount we knew about the intricacies of the cancer cell increased exponentially, and with it, everything became exceptionally more complicated, messy and difficult. Of course, knowledge is what we are aiming for – but when this influx of knowledge is so massive and intricate and mind numbingly complicated, the true benefit of it can be masked. It was very much a case of the more we looked, the more complicated the picture became, and hence the further away the “answer” or “cure” seemed.
Although both scientists have successful careers researching their own specific part of the picture within the cancer cell; their career fame was catapulted by something else. What Douglas Hanahan and Robert Weinberg set out to do, was to streamline the explosion of cancer biology into understandable and logical chunks. To find method in the madness. They took a step back from all of the actual experimental results and looked for themes. How can we understand conceptually what is going on here? How can we move this forward?
In January 2000 Hanahan and Weinberg published their paper “The Hallmarks of Cancer” in the prestigious journal Cell, and to date it is the most cited paper Cell has ever published. Below is the original iconic image (which has been later updated with additional hallmarks in 2011), that has shaped a generation of cancer research.
The portrait of the enemy.
Quick fire term breakdown:
apoptosis: Programmed cell death
angiogenesis: New vessel growth
metastasis: Ability to move from the site of origin
Briefly; what they did was try to categorise all of the research that was coming out into themes, and identify the archetypal “Hallmarks” of a cancer cell. What does this mass of science tell us about how the cancer behaves at a fundamental level, that makes it different to a normal cell. This is key. Why? Because the very nature of cancer, in that it originates from one of our own cells gone abit awry; means it is particularly difficult to treat –its verrryyy like all of our own other healthy cells. If you are trying to catch a bear in a room of cats, you have a pretty good chance of finding it. Catching your required bear in a room full of bears is a lot more difficult. No recommendation for catching bears, btw.
By carefully pinpointing the small differences between healthy cells and cancer cells, the field was able to focus on developing strategies to target only the cancer cells. Traditional chemotherapeutic treatment strategies work as whole body toxins which cause DNA breaks in cells which divide; their forte lies in the fact that cancer cells divide and grow quite rapidly, but guess what – loooottss of healthy cells divide and grow too! Hence those nasty side effects of chemo. What we term the “therapeutic window” of these agents – the difference in the dose between them killing cancer cells and killing normal cells is small. On the other hand, the shift enabled by cancer biology, helped in part by Hannahan and Weinbergs Hallmark paper, are part of a wave termed “Targeted therapeutics” – in essence, if we can find aspects of a cancer cell that are specific or particularly different than normal cells, we design drugs to target those, specifically kill cancer cells and save normal cells. Like all of biology, this is a lot more complicated, intricate and difficult than I’ve just breezed through – but that’s the basic idea.
So, Hanahan and Weinberg played a role in painting a detailed picture of the cancer cell, which not only will be handed to you as a young cancer researcher to study, but has helped to develop many cancer research areas and drug development routes. In another blog post, I’ll delve a little deeper into one of two of the hallmarks and explore how they have shaped targeted therapy and where we currently stand in getting these targeted therapies to patients.
Get to know your enemy, and all that.
Links for those wonderful curious souls:
Original paper (2000): The Hallmarks of Cancer. Hanahan & Weinberg.
Updated paper (2011) The Hallmarks of Cancer: The Next Generation. Hanahan & Weinberg.