“Cure for all cancers” – Hype or breakthrough?

“New hope of cure for all cancers” declared the Daily Express front page on Monday morning, while the Daily Mail chimed in with “Major breakthrough in cancer research.” A somewhat more sedate Times opted for “Better cancer drugs likely after protein breakthrough.” It’s obviously big – and exciting – news, but what’s this story all about?

The media kerfuffle is over a paper published online in the journal Nature, from Emmanuel Skordalakes and his colleagues at the Wistar Institute in Philadeplphia. At the heart of the story is a molecule called telomerase – a well-known ‘suspect’ in cancer research.

In this work, the researchers have studied the molecular nature of telomerase extracted from the red flour beetle (a household pest), describing its structure almost down to the atomic level. This seems a bit anti-climactic after the huge headlines about cancer cures, so why is telomerase so interesting, and why is this discovery important?

Telomerase and cancer
Cells multiply by a process confusingly known as cell division. We need cell division on a grand scale to keep us healthy – to grow and develop, to heal injuries, and to replace dead and worn-out cells.

Cancer is a disease caused by cells multiplying out of control, so to prevent this from happening during the billions of cell divisions that happen during a lifetime there are many ‘checks and balances’ in place. One good example of this control is telomerase, or rather a lack of it.

All of our cells contain DNA, packed into long, thin bundles called chromosomes. Chromosomes have ‘caps’ on their ends, like the plastic bits at the end of shoelaces. These caps are called telomeres – they are complex structures made up of DNA and protein that protect our precious genes. But this protection fades with time because whenever a cell divides, its telomeres get a little bit shorter.

The molecular clock
Over time, and many divisions, the telomeres eventually become so short that they no longer protect the DNA. At this point, the cell realises things are going awry and stops dividing, in order to avoid causing any damage to its genes. Effectively, telomere shortening acts as a molecular ‘hourglass’, limiting the number of times a cell can divide – this offers us a very potent protection from cancer.

But cancer cells manage to get round this self-limiting system, by re-activating telomerase – an enzyme that can rebuild telomeres. Telomerase is normally only active in the cells of embryos, which need to multiply many times. In adults, it gets switched off except in a very few specialised cells. By reactivating telomerase, cancer cells essentially become immortal, cheating the molecular clock and multiplying ad infinitum.

Targeting telomerase
Researchers have found that telomerase gets reactivated in around 8 out of 10 cancers, of many different types. This, and the fact that it is switched off in most adult tissues, makes it an extremely attractive target for potential cancer drugs. Researchers around the world, including some funded by Cancer Research UK, have been investigating telomerase for many years, searching for ways to switch it back off in cancer cells.

But progress has been achingly slow, partly due to the fact that – until now – we haven’t really got to grips with the atomic structure of telomerase. This is important because we can’t design drugs to effectively block telomerase if we don’t know exactly what it looks like at a sub-microscopic scale.

Solving the structure
In their new paper, Skordalakes and his team probed the molecular structure of telomerase from the red flour beetle. This may seem like an unusual choice of organism, but it still holds plenty of relevance for human cancer, as telomerase is very similar in virtually all animals.

Their research has given us some extremely valuable insights into the ‘nuts and bolts’ of telomerase and how it works. In this context, it’s an extremely important piece of science – not because it will lead to new cancer drugs tomorrow, or even in the next year or two (which it probably won’t), but because it shapes the direction of research for the hundreds of scientists around the world who are working hard to target telomerase.

So is it a breakthrough?
If we’re going to be picky about the headlines, it’s not going to provide a “cure for all cancers” – although around 8 out of 10 cancers switch telomerase back on, there’s still 2 in 10 that don’t. These cancers use a different mechanism to maintain their telomeres, and so are unlikely to respond to telomerase-blocking drugs.

However, for researchers working in the field of telomerase research, this paper could certainly be described as a breakthrough. More generally in the field of cancer science, it’s certainly a very important discovery. It’s not the be-all-and-end-all of cancer research, and there are certainly many other fruitful avenues that we need to explore. But it’s a big step in the right direction towards telomerase-targeting drugs for treating cancer in the (hopefully not-too-distant) future.

Kat