2010 NCRI conference: The hallmarks ofcancer
Doug Hanahan addresses the NCRI Conference.
There are over 200 different types of cancer that affect virtually every organ in the body. They can seem bewilderingly different but all cancers share certain features that make them… well, cancer.
In January 2000, US cancer experts Doug Hanahan and Bob Weinbergpublished a seminal paper called “The Hallmarks of Cancer”, which outlined six of these common features. The article appeared in the Millennium issue of the journal Cell, and it went on to influence a generation of cancer researchers.
Nowadays, their ideas are regarded as established fact. The paper has since been referenced by others over 10,000 times, and was downloaded 20,000 times a year between 2004 and 2007.
Ten years later, at the 2010 NCRI Cancer Conference, Doug Hanahan flew in from Switzerland to give us his thoughts about how our understanding has progressed in the intervening years and – crucially – what this means for developing more effective ways to treat cancer. He even added a couple of new hallmarks.
Six hallmarks
In their original review, Hanahan and Weinberg proposed the following ‘hallmarks’ – features that cells acquire as they become cancerous:
1. Self-sufficiency
The cells of our bodies are, in effect, members of a huge support group. They constantly supply each other with encouraging messages, telling their neighbors that “everything’s OK” and to stay where they are.
In contrast, cancer cells behave like arrogant, self-important egomaniacs. They only listen to their own internal voice, and despite all evidence that they’re behaving in an anti-social manner, carry on regardless.
2. Insensitivity
Needless to say, when a cell starts misbehaving, its neighbors kick up a fuss, sending messages telling it to play nicely with the rest of the group. A second hallmark of cancer is that, metaphorically speaking, it can stick its fingers in its ears and ignore the clamor from next door telling it to cease and desist.
3. Invasiveness
Perhaps the most well-known feature of cancer cells is their wanderlust. Unlike healthy cells, which generally stay in one place, cancer cells acquire the ability to roam around the body to find new homes. This ability to invade and spread – known as metastasis -is actually what makes cancer a deadly disease.
4. Immortality
Each time a cell divides, it picks up a few tiny errors in its DNA. The more times it divides, the more errors it accumulates. This acts like a molecular ‘clock’, limiting the number of times that most cells can divide in a lifetime. Cancer cells bypass these mechanisms, and can divide again and again, becoming more and more error-strewn and abnormal as they do so.
5. Greed
We all need oxygen and nutrients to keep us going, and cancer cells are no exception. They’re masters at subverting the body’s pipelines – our blood vessels – for their own purposes. This particular hallmark of cancer – the ability to grow new blood vessels, or angiogenesis – is so important that it’s become a major focus of efforts to target the disease, as we’ve written about before.
6. Cheating death
‘Apoptosis’, also called ‘programmed cell death’ or cell suicide, is another one of nature’s anti-cancer tricks. Cells that become damaged or dysfunctional have a number of internal trip-wires that cause them to self-destruct, but – as you might expect – cancer cells manage to defuse these booby traps and carry on growing.
A decade on – new insights
Since their article appeared in 2000, research – and our understanding of cancer – has moved on. Hanahan and Weinberg have been writing an update, and Hanahan shared some of the pair’s latest thinking with us. They’ve now added four more characteristics to their list:
7. Deregulated energy supplies
The idea that cancer cells generate energy differently from normal cells has been around since the 1920s, and there’s now a substantial body of evidence that this is the case. This unusual mode of energy production is a hot topic in cancer research, and scientists are trying to exploit it to develop more effective treatments.
8. Masters of disguise
We now know that our immune system plays an important role in protecting us against cancer, by spotting rogue cancer cells and nipping them in the bud. So for a cancer to develop, its cells need to escape detection by the immune system.
How they do this, how to prevent it, and how we can use the power of the immune system to destroy cancers is another major focus of research around the world.
9. Instability
Cancers have unstable DNA – a fact that’s been known for several decades. Tumor cells are continually mutating and evolving, scrambling their DNA into an almost unrecognizable state.
Hanahan admitted that there’d been some debate about whether this was in fact a ‘hallmark’ of cancer, or a feature that enabled cancer cells to acquire other characteristics. But to recognize the importance of genetic instability and mutations, they decided to include it in their revised list.
10. Inflammation
We’ve bloggedmanytimes about the importance of inflammation in the development of cancer, and Weinberg and Hanahan felt it important enough to include as a hallmark of the disease. They added the caveat that it’s not a feature of cancer cells themselves, but an effect they have on their surrounding environment.
Hanahan also mentioned three other aspects of cancer that have gained in importance over the last decade. Firstly is the view that a tumor is not a uniform ‘bag of cancer cells’ – it’s more akin to a small ‘rogue organ’, made up from many different types of cell – stem cells, immune cells, supporting cells and blood vessels – all working together to sustain the tumor.
Secondly, he emphasized the importance of what’s becoming known as ‘systems biology’ – the study of an entire system rather than its component parts. This involves understanding the messages produced by cancer cells and their surrounding neighbors, the signals that are sent within these cells, and how all of these join together to form a ‘molecular circuit board’.
Finally he spoke about the recognition that cancer doesn’t develop down a single, linear path. Cancers aren’t static, they’re dynamic, living entities that grow, retreat, speed up, slow down, and constantly change. Unfortunately, this makes them much harder to target than was optimistically thought ten years ago. But it’s an important realization that’s now guiding cancer researchers.
What are the hallmarks of cancer?
Yuri Lazebnik
Abstract
A major goal of cancer research is to understand how to counteract mechanisms that underlie the ability of cancers to kill the patient or, in other words, to be malignant. To this end, the puzzling complexity of numerous and interrelated properties of cancers was distilled 10 years ago into “six essential alterations in cell physiology that collectively dictate malignant growth: self-sufficiency in growth signals, insensitivity to growth-inhibitory (antigrowth) signals, evasion of programmed cell death (apoptosis), limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis” (Douglas Hanahan and Robert Weinberg).