A few days ago, news reports claimed that 16 per cent of cancers around the world were caused by infections. This isn’t an especially new or controversial statement, as there’s clear evidence that some viruses, bacteria and parasites can cause cancer (think HPV, which we now have a vaccine against). It’s not inaccurate either. The paper that triggered the reports did indeed conclude that “of the 12.7 million new cancer cases that occurred in 2008, the population attributable fraction (PAF) for infectious agents was 16·1%”.
But for me, the reports aggravated an old itch. I used to work at a cancer charity. We’d get frequent requests for such numbers (e.g. how many cancers are caused by tobacco?). However, whenever such reports actually came out, we got a lot confused questions and comments. The problem is that many (most?) people have no idea what it actually means to say that X% of cancers are caused by something, where those numbers come from, or how they should be used. Read More
When I used to work at a cancer charity, I would often hear people asking why there isn’t a cure yet. This frustration is understandable. Despite the billions of dollars and pounds that go into cancer research, and the decades since a war on cancer was declared, the “cure” remains elusive.
There is a good reason for that: cancer is really, really hard.
It is a puzzle of staggering complexity. Every move towards a solution seems to reveal yet another layer of mystery.
For a start, cancer isn’t a single disease, so we can dispense with the idea of a single “cure”. There are over 200 different types, each with their own individual quirks. Even for a single type – say, breast cancer – there can be many different sub-types that demand different treatments. Even within a single subtype, one patient’s tumour can be very different from another’s. They could both have very different sets of mutated genes, which can affect their prognosis and which drugs they should take.
Even in a single patient, a tumour can take on many guises. Cancer, after all, evolves. A tumour’s cells are not bound by the controls that keep the rest of our body in check. They grow and divide without restraint, picking up new genetic changes along the way. Just as animals and plants evolve new strategies to foil predators or produce more offspring, a tumour’s cells can evolve new ways of resisting drugs or growing even faster.
Now, we know that even a single tumour can be a hotbed of diversity. Charles Swanton from Cancer Research UK’s London Research Institute discovered this extra layer of complexity by studying four kidney cancers at an unprecedented level of detail. He showed that the cells from one end of the tumour can have very different genetic mutations to the cells at the other end.
These are not trivial differences. These mutations can indicate a patient’s prognosis, and they can affect which drugs a doctor decides to administer. The bottom line is that a tumour is not a single entity. It’s an entire world.
I’ve written a few guest posts for the Faculty of 1000’s Naturally Selected blog, covering some interesting papers from last year that I missed here. There’s one about how eggs greet sperm, and another on how sleeping alone affects newborn babies. But the third post is one that I particularly want to draw attention to – it’s about a cancer paper that didn’t get much notice last year, but seems to deserve it. Here’s the first bit:
Tumours are bundles of cells that grow and divide uncontrollably, and their genes are deployed in unusual ways. By analysing the genes from different tumour samples, scientists have tried to pin down the chaotic events that lead to cancer. They seem to be making headway. Dozens of papers have reported “gene expression signatures” that predict the risk of dying or surviving from cancer, and new ones come out every month.
These signatures purportedly hint at how healthy cells transform into tumours in the first place. If, for example, the genes in question are involved in wound healing, this tells you that the healing process is somehow involved in a tumour’s progression. These collections of genes reveal deeper truths about the disease they’re associated with.
This idea sounds reasonable, but David Venet from the Université Libre de Bruxelles has thrown a big spanner into the works. He has shown that completely random sets of genes can predict the odds of surviving breast cancer better than published signatures.
Venet found three signatures that are completely unconnected to cancer. Instead, these collections of genes were associated with laughing at jokes after lunch, with the experience of social defeat in mice, and with the positioning of skin cells. All of them were associated with breast cancer outcomes.
Head over to Naturally Selected for the rest, including how long it took to get this study published.
Image by Hakan Dahlstrom
As we get older, many of the cells in our bodies go into retirement. Throughout our lives, they divided time and again, all in the face of radiation bombardments and chemical attacks. Slowly but surely, their DNA builds up damage to that threatens to turn them into tumours. Some repair the damage; others give up the ghost. But some cells opt for a third strategy – they shut down. No longer growing or dividing, they enter a state called senescence.
But they aren’t idle. Senescent cells still secrete chemicals into the body, and some scientists have suggested that they’re responsible for many of the health problems that accompany old age. And the strongest evidence for this claim comes from a new study by Darren Baker from the Mayo Clinic College of Medicine.
Baker has developed a way of killing all of a mouse’s senescent cells by feeding them with a specific drug. When he did that in middle age, he gave the mice many more healthy years. He delayed the arrival of cataracts in their eyes, put off the weakening of their muscles, and held back the loss of their body fat. He even managed to reverse some of these problems by removing senescent cells from mice that had already grown old. There is a lot of work to do before these results could be applied to humans, but for now, Baker has shown that senescent cells are important players in the ageing process.
It’s a seemingly simple idea: if you can find the genetic changes that turn normal cells into cancerous ones, you could find new ways of treating cancer. But that’s easier said than done. The genome of a cancer cell is a chaotic mess. Typos build up throughout its DNA, corrupting the encoded information. Entire sections can be flipped, relocated, doubled and deleted. Some of these changes drive the cells to grow and multiply uncontrollably; others are irrelevant passengers that are just along for the ride. Separating the former form the latter is like finding a needle in a haystack made of needles.
And that’s exactly what Elisa Oricchio from the Sloan-Kettering Memorial Cancer Center has done. Using powerful genetic techniques, she has identified a gene – EPHA7 – whose loss can lead to a sluggish but hard-to-treat type of lymphoma called follicular lymphoma. The gene encodes a protein of the same name, and Oricchio even used the EPHA7 protein to shrink the size of tumours in mice with lymphoma.
It is easy enough to make software do what you want it to. You could tell your email client to recognise and immediately delete any unwanted messages – say, any from your mother-in-law that contain the word “visit”, but not the word “cake”. Now, Zhen Xie from Harvard University and MIT has found a way of filtering undesirable human cells – in this case, a specific type of cancer cell – with similar ease.
Xie has developed a genetic “logic circuit” that prompts cells to kill themselves if the levels of five molecules match those of a cancer cell. Yaakov Benenson, who led the study, says, “In the long term, the circuits’ role is to act like miniature surgeons that can identify and destroy cancer cells.” That is a very long way off, but the study is a promising step in the right direction.
Around a third of us are infected with a brain parasite called Toxoplasma gondii. This single-celled creature spreads to humans from cats, and has a tendency to change the behaviour of its hosts. Now, a team of scientists led by Frederic Thomas and Kevin Lafferty have found that countries where more people are infected with the parasite have higher rates of brain cancer.
This does not mean that T.gondii causes brain cancer, or even that the two are actually linked. Patricia McKinney, who studies brain cancer and was not involved in the study, says, “This is a technically sound hypothesis-generating paper and, viewed as such, is interesting. It doesn’t tell us much, other than pointing towards some further investigation.”
In Dunn County, North Dakota, the roads are paved with a unique danger. Over 300 miles of them are covered with gravel taken from the local North Killdeer Mountains. This rock is rich in a mineral called erionite that behaves not unlike asbestos. Both cause cancer, but according to animal studies, erionite is anywhere from 200 to 800 times more effective at it than its more famous counterpart.
Dunn County’s erionite gravel releases small brittle fibres into the air when lightly disturbed. They’re released by wheels driving overhead, the footfalls of pedestrians, or even the gentle scrapes of brooms and rakes. Once airborne, the fibres can find their way into the lungs of passers-by, accumulating in the surrounding cavity (the pleura). There, they cause chronic inflammation and, over time, a type of cancer called mesothelioma.
To date, no one in Dunn County has been diagnosed with mesothelioma as a result of erionite, but It is only a matter of time. The first such cases in North America have already been reported. And to see what the future holds, you only have to look 6,000 miles away at the Cappadocia region of Turkey.
Our bodies are rife with disappearing potential. We come from stem cells, which can give rise to all the diverse types of cells in the human body. They can produce neurons, muscle cells, skin cells and more. As their daughters become more and more specialised, they lose this ability and become stuck with a specific fate.
That’s the standard story – a one-way street of lost potential.
The story is wrong.
According to a provocative new study from Christine Chaffer at the Whitehead Institute for Biomedical Research, some specialised cells can spontaneously revert back to a stem-like state. The one-way street actually works two ways.
It’s a very surprising result. Until now, no one thought that these reversions were possible, and scientists have spent a lot of effort finding ways of artificially reprogramming specialised cells into a stem-like state. Now it turns out that cells can naturally do the same thing. It’s like suddenly discovering that the people you pass every day in the street have been secretly gaining superpowers under your nose.
CTVT, or canine transmissible veneral tumour, is a cancer that has evolved into an independent global parasite. Most cancers (including those that affect humans) aren’t contagious. Although some infectious diseases can lead to cancer, you cannot actually catch a tumour from someone who has one. But CTVT is an exception – the cancer cells themselves can spread from dog to dog, through sex or close contact.
A Russian veterinarian called Mstislav Novinsky first discovered the disease in the 1870s, but it took 130 years for others to discover its true nature. In 2006, Robin Weiss and Claudio Murgia from University College London compared CTVT samples from 40 dogs across the world. All of them carried distinctive genetic markers that set them apart from the cells of their host dogs. They all had a common ancestor – an ancient tumour that escaped from its original host and took the world by storm.