The Grand Challenge - can you solve this problem?

Cancer Research UK

In October Cancer Research UK (CRUK) launched the癌症研究英国大挑战赛– a £100m scheme to tackle seven of the biggest challenges in understanding and treating cancer.

在接下来的两个月中，他们将探索每个帖子七个大挑战问题set by a panel of the world’s leading cancer experts, starting with question one:Can we develop vaccines to prevent cancers that aren’t caused by viruses?

Many of us will be familiar with the idea of疫苗– one of the greatest advances in medicine – which trigger our immune systems to recognize and attack infectious diseases. Vaccines remain the only medical advance to have ever fully eradicated a disease, ridding the world of the smallpox virus.

但是最大的问题是：疫苗可以为癌症做同样的事情吗？显然，癌症不是感染的 - 与细菌和病毒不同，它们是从我们自己的细胞发展而来的，对我们的免疫系统构成了巨大的挑战，以识别它们是有害的。

然而，利用免疫系统与癌症作斗争的力量已经存在a goal for scientists for over a century. But it’s only recently that we’ve begun to understand exactlyhowimmune cells (mistakenly) view cancer as a friend to leave in peace, rather than an enemy to destroy. And then harness this knowledge to开发新的癌症治疗.

But this has also raised the question of whether we might be able to use vaccines to prevent – as well as treat – the disease.

Immune surveillance

Vaccines work by training the immune system to recognize small, harmless pieces of a disease, so that it can eradicate anything that looks like it in the future. Once convinced that a particular molecule belongs to the enemy, the immune system is forever primed to treat it as hostile.

Vaccines have already been developed against certain forms of cancer that arecaused通过病毒，这样的人乳头瘤病毒（HPV）– which causes cervical, oral and anal cancers. And eradicating癌症s caused by the Epstein Barr Virus(EBV) – such as certain forms of lymphoma – is the第二个挑战问题的第二(more on this to come in the next of the series). So the idea of creating a vaccine to prevent or treat cancers linked to viruses certainly works in theory.

但是，每年英国每100次癌症中只有三种与感染有关。在这些情况下，免疫系统的目标是不同的 - 绝对是“外国”。

Without that ‘foreign invader’, alerting the immune system becomes a lot more complicated.

So the first challenge set by our panel is to take this a step further, and find a way to directly target cells in our bodies in the earliest stages of becoming a cancer. Helping the immune system destroy these abnormal cells before they develop into cancer could not only save lives, but spare thousands fromeven becoming a cancer patient in the first place.

这听起来不可思议 - 那么这在实践中如何工作？

What do we mean by a cancer jab?

Professor Tyler Jacks, director of theKoch Institute for integrative cancer research at MITin the US, and one of the members of our Grand Challenge scientific panel, redibly excited by the prospect of this question.

“To be clear, the point is not to have a one-size-fits-all vaccine preventing all cancers,” he explains.

“Every cancer is different. But I would be happy, I would be thrilled actually, if this question stimulated research that found a set of molecules, probably not just one, which we could develop into a vaccine for people at a higher risk of certain cancers.”

Professor Christian Ottensmeier, a Cancer Research UK expert in immunology at the University of Southampton, shares his enthusiasm. “It’s entirely possible that as a result of this Grand Challenge people will start to look at the puzzle of preventative vaccination in a different way,” he says.

“So I’m really excited about this opportunity, because I think this will make the research community look at this particular question in a way it hasn’t so far.”

但是创建一个疫苗来预防癌症更容易said than done, and Professor Jacks sees several important steps that must be overcome, each with its own unique challenges and hurdles. But the biggest, he says, is the first – finding targets for the vaccine that are hallmarks of developing cancer cells.

Spotting cancer before it happens

Finding suitable vaccine targets requires researchers to pinpoint molecules that the immune system can recognize as ‘foreign’. These are known as“抗原”.

杰克斯说：“我们知道癌症由于DNA的变化而发展。”“这些遗传错误中的一些会导致分子看起来与正常健康细胞中应如何应对。如果我们能找到某些类型的癌症中的哪些突变很常见，那么我们也许可以在疫苗中使用它们来针对该癌症类型。”

除了这些故障的“自我”分子之外，研究人员还发现，某些形式的癌症在不应该时会产生正常的分子，或者比健康细胞大得多。这些被称为‘tumour-associated antigens’. For example, a molecule that’s only made during early childhood and not at all in a healthy adult might be switched back on and produced inside cancer cells to help them grow.

And as well as these faulty or inappropriately produced molecules, there could be an entirely new method for finding the best targets.

According to Ottensmeier it’s difficult to know what the explosion in data generation will lead to.

他说：“即使是三到五年前，您甚至可以考虑将患者特异性疫苗进行。”

“But now that’s already a reality with a number of bespoke, experimental ‘vaccines’in development as treatments.”

Finding the target is just the first step

Once a suitable collection of vaccine targets are found, there would then be a huge amount of work to make sure the vaccine actually worked, and was safe.

Neither of these will be easy. And since the goal is to create something that protects over a lifetime, it won’t be quick either. It could take decades to ensure that a vaccine preventing cancer in the general population truly works.

但是，Ottensmeier并没有实现这一最终目标，而是认为更好的策略 - 在我们巨大的挑战时间内可能可以实现的策略可能是识别并开始开发可以在一小群高风险患者中使用的疫苗 -例如，患有乳腺癌家族史的妇女。

“Women with known faults in their DNA are already offered preventative measures,” he says.

对于某些人来说，这可能涉及双乳房切除术，例如备受瞩目的女演员和电影制片人安吉丽娜·朱莉（Angelina Jolie）在2013年.

“但是，如果我们可以为这些妇女提供针对乳腺癌而不是手术的疫苗，该怎么办？”问Ottensmeier。这是一个诱人的前景。

病人的观点

– Terry, patient panel member for the Grand Challenge

High hopes

一个巨大的挑战应该具有挑战性，不应该显而易见。由申请人提出解决这个问题的最佳方法，但是如果成功的话，奖励可能会令人难以置信。

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Professor Jacks
Director of the Koch Institute for integrative cancer research at MIT

Our understanding of the immune system has come on in leaps and bounds in the last decade, and the resulting progress in immune-based treatments has made things possible that were previously considered completely untenable.

So, in a period of such rapid progress, Professor Jacks argues: “Why not reach for the stars a little bit here”.

“一个巨大的挑战应该具有挑战性，不应该显而易见。由申请人提出解决这个问题的最佳方法，但如果成功，奖励可能会令人难以置信。”

And being on the cusp of discovery is exactly how this type of research should be carried out. “Honestly, we just don’t know if we can do this,” he says.

“But failure in research is commonplace. We make progress despite a great deal of failure.

“If you don’t try, you’ll never succeed, and just because it might not work is no reason not to try.”

If you’re a researcher and want to build a team to take on this challenge,visit CRUK’s website to find out how you can apply.