我的Cacts as a 'conductor', directing a range of vital processes inside cells.

Wikimedia Commons/Persian Dutch Network

Researchers already know how to theoretically cure a significant proportion of all human cancers. The problem is actually doing it.

At the heart of this challenge lies a molecule called我的C。就像指挥家指示乐团的所有各个部分与和谐一起工作一样，MYC协调了细胞内部许多不同基因的作​​用，以使事物顺利进行。

From controlling cell division and growth, to instructing faulty cells to die, MYC has been linked to a wide range of fundamental biological processes – something we’ve written about in depth inthis post。And, unsurprisingly for such a ‘super-controller’, faults in MYC have been linked to many different types of cancer.

Researchers have long known that faulty, overactive versions of MYC can lead to cells dividing out of control – like a conductor whipping an orchestra into a chaotic, frenzied crescendo – ultimately leading to cancer.

实际上，从多达十分之七的各种肿瘤中发现了过度活跃的MYC，从aggressive lung cancers到childhood brain tumors。As a consequence, researchers around the world have focused a huge amount of effort on trying to switch it off.

不幸的是，关闭MYC正在成为一个非常复杂的难题。这就是为什么我们设定了解决它的挑战。

Switching MYC

尽管研究人员自1980年代以来就了解了MYC，但它在细胞内部做许多不同的事情这一事实意味着它往往被忽略为癌症药物的靶标。

Surely, the argument goes, it’s impossible to hit MYC, and stop cancer cells dividing, without also messing up all the other vital processes it’s involved in?

But in the past five years or so, a team of Cancer Research UK-funded researchers in Cambridge have proved everyone wrong.

他们使用基因工程技术创造了小鼠，其MYC基因可以在整个身体中专门关闭。当这些动物发生肺癌时，关闭了MYC完全杀死癌细胞。

Importantly, the treatment only caused mild, reversible side effects, suggesting the impact of temporarily blocking MYC in the rest of the body – which is what would happen with a drug – might not be as severe as was first thought.

These remarkable results re-ignited interest in targeting MYC as a potential cancer cure. But the system that Cambridge team used relies on complex genetic engineering – something that’s not technically or ethically possible in humans – and the hunt is on to find drugs that can stop MYC in its tracks.

但是，正如我们的首席科学家Nic Jones教授告诉我们的那样，这并不是一件简单的任务：“所有证据都表明MYC是一个很好的目标，并且已经努力开发药物来阻止它。但是到目前为止，这些努力已经失败，这将采取完全不同的思维方式来实现它。”

了解该故障的原因解释了为什么针对MYC是一个如此巨大的挑战。

吸毒不足

The targets of most ‘smart’ drugs, such astrastuzumab (Herceptin)orvemurafenib (Zelboraf)，通常是在癌细胞内或内部发现的信号分子。这些往往具有明确定义的形状和结构，并带有整洁的生物学“口袋”，可以将药物插入，就像钥匙配合到锁中一样。

我的Cis a very different beast. It’s a type of protein known as a转录因子，，，，responsible for sitting on special stretches of DNA next to genes and switching them on. To do this it needs to be very flexible, buddying up with another factor called最大限度（或其他合作伙伴蛋白质之一）并将其模制成正确的形状，以固定在DNA的双螺旋中。

Dr Martin Drysdale, head of the Drug Discovery programme at our Beatson Institute in Glasgow, describes MYC as being “like a disordered strand of spaghetti – it has no defined shape until you attach it to MAX or another partner. And there was always this feeling that targeting transcription factors like MYC was difficult, because people have tried to find things in the past and been singularly unsuccessful.

“It comes down to the complexity of how they work from a biological point of view, but also a lack of information about their shape, and how drugs might interact with them.”

What’s clear after several frustrating years is that our methods of finding cancer drugs – either trying to design a molecule to slot into a pocket in a target, or looking at thousands of different chemicals to find ones that fit – simply aren’t working for MYC.

It’s time for some completely new ideas.

Fresh thinkers needed

“In terms of thinking about the MYC Grand Challenge, what we’re really looking for is innovation in drug discovery,” explains Professor Jones. “People coming together – people who don’t necessarily work on MYC, but who have an interest in drug discovery in general, and thinking about the ways in which we could develop drugs against proteins that are difficult to target in the conventional way.

Nobody has been able to do this before. If it’s successful, it will be transformational

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尼克·琼斯教授

“If we get a consortium that comes in and says ‘we’re going to look at a ‘library’ of small chemicals’, well, that’s not going to fly because it’s been done and it doesn’t work. It’s got to be different, and it’s got to be new.”

有一些有趣的方法可能起作用。例如，德里斯代尔（Drysdale拉斯，寻找粘在其上的微小片段。MYC可以采用类似的策略吗？

Biological molecules such as antibodies – highly specific target-hunting molecules generated by immune cells – could be interesting too. As weexplain in this postabout our new lab in Cambridge, researchers are ‘fishing’ for antibodies that recognize rogue molecules involved in driving cancer, with the hope of finding future cures. So maybe a fishing trip with MYC could be a good idea.

MYC甚至不必成为主要目标。靶向MYC的分子伙伴或涉及的细胞过程和途径的组成部分，无论是传统药物，抗体还是全新的方法可能会带来好处。

更重要的是，根据琼斯的说法，解决吸毒MYC的问题可能会在将来对癌症患者带来更多的好处。“有充分的理由选择了MYC，但我们希望我们能刺激可能适用于其他不良分子的想法。”

他相信,针对MYC基因是一个艰难但chievable task, making it eminently suitable for a Grand Challenge. “I think the simplicity of it, the clarity of it and the potential to benefit patients in a reasonable timeframe makes it a very attractive challenge.

“有些人可能会认为，因为这是一个特定的问题，所以并不大。但是以前没有人能够做到这一点。

“If it’s successful, it will be transformational.”

The patient perspective

- 玛格丽特（Margaret），大挑战赛患者小组的成员