Cancer Evolution

[gareb]

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A world within a tumour – new study shows just how complex cancer can be
Ed Yong
Not Exactly Rocket Science | Discover Magazine

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.

This is one of the tumours that Swanton worked with. It was removed from the kidney of a patient being treated for cancer London’s Royal Marsden hospital. Swanton’s team took nine samples from different parts of the fist-sized mass, as well as other places where it had spread to – the space around the kidney and the patient’s chest.

Swanton found that even the primary tumour was surprisingly varied. He found 128 mutations among the various samples, but only a third of these were common to all of them. A quarter of the mutations were “private” ones – unique to a single sample.

The tumour had also split down two evolutionary lines. One area – part of R4 in the picture – had doubled its usual tally of chromosomes and seeded all the secondary tumours in the patient’s chest. The other branch had spawned most of the primary tumour’s mass. Even though the tumour is a single mass, whose cells all descended from a common ancestor, the different parts are evolving independently of one another.

For example, Swanton found that only one known kidney cancer gene – VHL – was consistently mutated throughout the tumour. It was the only one present in the “trunk” of the tumour’s evolutionary tree. The two main branches each picked up their own mutations. However, Swanton also found signs of convergent evolution, where different populations hit on the same adaptations on their own. In this case, three separate parts of the main tumour had disabled the same gene – SETD2 – in different and independent ways.

Three other kidney tumours showed the same degree of bewildering variety and convoluted history.

Darryl Shibata, a cancer geneticist from the University of Southern California, compares Swanton’s approach to the standard medical practice of taking a patient’s history. “By listening to a patient, a wise MD can just about predict what they will find on lab tests,” he explains. “An MD who simply orders tests will get back a baffling list of abnormal findings.” Likewise, reconstructing the evolutionary history of a tumour can make sense of the baffling array of mutations it contains. “Nothing in biology makes sense except in the light of evolution,” adds Shibata, quoting the famous biologist Theodosius Dobzhansky.

(continue reading the full story here.)

[chris_bern]

I hope someday naa na jud CURE aning cancer...

[genx]

naay bago nga study about stem cell therapy..ambot ug makaya ba ayuhon ani nga therapy..hopefully, for everyone's benefit.

[gareb]

On the origin of tumours - Cancer Research UK - Science Update blog