人類離贏得"癌症戰爭"勝利的距離(2)

Adult cells are constantly under strict control, Weil says. "Basically Cancer is a loss of control of those cells."

“成年的細胞是被持續的嚴格控制的”，韋爾說，“基本上我們可以把癌症理解爲對這些細胞失去了控制。”

Cancer can only grow in this uncontrolled fashion if some of the genes that usually stop any accidental cell growth – such as the p53 gene – get mutated in the cancer cells.

通常情況下我們人體內的某些基因會阻止細胞意外生長，比如 P53基因，但如果他們在癌細胞中發生突變，那麼癌細胞就會在這種失控的模式下成長。

However, our bodies are pretty good at spotting these mutations. There are biological systems within us that step in to destroy most mutated cells before they can cause us harm.

當然我們的身體非常善於識別這些突變。我們身體內部的生物系統會在突變細胞對人體健康產生危害時摧毀突變最嚴重的細胞。

We have several "corrective" genes which send instructions to kill any corrupted cells. "There's millions of years of evolution that's gone into this," says Charles Swanton of the Francis Crick Institute in the UK. "It's pretty good but it's not quite perfect."

在我們身體內部有一些負責“糾正錯誤”的基因，他們會指導我們殺死那些腐壞的細胞。“上百萬年的進化讓我們的身體非常善於修正錯誤，”英國弗朗西斯•克里克研究所（Francis Crick Institute）的教授查爾斯.斯旺頓（CharlesSwanton）說到。“基因在這方面非常強大，但是並不完美。”

The threat comes from the tiny number of corrupt cells that do not get fixed. Over time, one of these cells can grow and divide into thousands, then tens of thousands of cancer cells. Eventually there may even be billions of cells in a tumour.

威脅就來自於這一小撮腐壞的但並沒有得到應有的修復的細胞。某一個未修復的腐壞的細胞通過分裂會變成幾千個，幾萬個癌細胞。最終，一個腫瘤中可能存活了幾十億個癌細胞。

This leads to a truly challenging problem. Once that initial corrupt cell has divided and multiplied into a tumour, a person will have cancer until every single one of the cancer cells has been obliterated. If just a few survive, they can rapidly multiply and regrow the tumour.

這引發了一個極具挑戰的問題，當一個腐壞的細胞通過分裂，生長成一個腫瘤的時候，我們就需要消滅每一個單獨的癌細胞，那麼這個患癌的人才可以被治癒。只要腐壞的細胞存活，哪怕只是很少的一部分，都可以迅速生長並形成腫瘤。

Cancer cells are not all alike: far from it. Whenever a cancerous cell divides, it has the potential to pick up new mutations that affect its behaviour. In other words, they evolve.

癌細胞並不相似，而且是非常不同。每一次癌細胞分裂，他們都有潛在的可能重新變異，也就是說癌細胞在不斷的進化。

As the cells inside a tumour mutate, they become ever more genetically diverse. Then evolution goes to work to find the most cancerous ones.

當癌細胞在腫瘤裏變異，他們的基因會變得越來越多樣化，在進化的作用下，變異就會主動去找這些細胞裏邊最惡性的細胞。

Genetic diversity is "the spice of life, it's the substrate upon which natural selection acts", says Swanton. By this he means evolution by natural selection, first proposed by Charles Darwin in 1859.

基因多樣性是“生活的調味品”，這是大自然的一種進化選擇的基礎，斯旺頓說。他的意思是通過自然選擇的進化，也就是查爾斯.達爾文在1859年首次提出的理論。

Just like individual species – humans, lions, frogs, even bacteria – gain genetic variation over time, so too do cancer cells. "Tumours don't evolve in a linear manner," says Swanton. "They evolve in a branched evolutionary manner, which means that no two cells in a tumour are the same."

癌症細胞通過進化而完成基因的多樣性，正如個體物種例如人類、獅子、青蛙、甚至細菌的進化方式。“腫瘤並不是線性的進化，”斯旺頓說。“他們通過分支進化的方式演變，也就是說同一個腫瘤中沒有兩個完全一樣的癌細胞。”

In effect, the cells of a tumour are evolving to become more cancerous. "Essentially we are dealing with branches of evolution that create diversity and that create fitness, and allow cell populations to survive therapy and ultimately outwit the clinician," says Swanton.

本質上，在腫瘤內的癌細胞會變得越來越致命。“實際上我們所做的就是針對進化中產生多樣性與健康的細胞分支進程，使細胞羣挺過癌症治療並最終取得良好的臨牀結果，”斯旺頓說。

The fact that tumours are constantly changing their genetic makeup is one of the reasons why cancers are so hard to "kill".

癌症之所以很難消滅是因爲腫瘤在持續不斷的改變他們的基因結構。

It is for this reason that Swanton, and others in the field, take an evolutionary approach to tackling cancer. Swanton, who specialises in lung cancer, is both a clinician and a research scientist. His work has revealed something that he hopes will help create effective, targeted treatment.

這就是爲什麼斯旺頓和其他研究人員採用進化性的眼光探尋着解決癌症的辦法。斯旺頓即是臨牀醫生也是理論科學家，他的專長是肺癌領域。他的研究工作已經揭示了癌症的一些工作原理，他希望這些成果可以幫助他最終找到更有效的精準治療癌症的方法。

Think of the evolution that goes on inside a cancer tumour as like a tree with many branches. At the base of the tree are the original mutations that triggered the tumour in the first place: mutations that should be shared by all of the cancer cells in the tumour.

我們可以把腫瘤內部的細胞進化過程想象爲一個長滿樹枝的大樹。樹根是觸動基因變異的機關：樹根細胞的變異影響到腫瘤內的所有細胞。

In theory, a therapy that targets one of those base mutations should destroy every cell in the tumour. This is an approach that some therapies already use. For instance a drug called EGFR therapy targets lung cancer, and a BRAF inhibitor protein attacks the faulty gene which can lead to melanoma.

理論上來說，如果任何一個療法可以精準定位這個樹根主幹突變，並且成功摧毀它，那麼就應該治癒了整個腫瘤。這也是現在很多治療使用的療法。比如針對肺癌的EGFR靶向治療藥物，還有針對導致黑色素瘤變異基因的BRAF抑制劑基因療法。

The trouble is, these therapies do not work as well as we might hope. Even in these targeted therapies, resistance often appears over time.

但是問題在於這些療法並沒有當初科學家們預期的有效，即使是在一些靶向治療中，時間一長就會出現耐藥性。

It occurs because there will be one or more cells in the tumour branches that has a resistance mutation that allows it to outwit the therapy, Swanton says.

“這是因爲一個腫瘤裏邊有一個或多個的癌細胞分支發生了突變，產生了耐藥性，因此治療失去了效果。”斯旺頓說。

In other words, some of the branches of the cancer tree have evolved in a way that makes them less vulnerable to attack through the base mutation. They can dodge the therapy.

換句話說，一些在腫瘤裏的分支癌細胞通過進化對針對於主幹突變的療法產生耐受性，因此躲過了靶向療法。

Swanton and his colleagues have studied the problem to see if they can develop a therapy with a better outcome.

斯旺頓和他的同事們已經注意到了這個問題，並且正在尋找新的方法，希望能夠得到更好的治癒辦法。

An average tumour might contain something like a thousand billion cancer cells. Some of those cells might well have evolved in a way that makes them immune to attack through a specific basal mutation.

平均一個腫瘤裏邊會保存着萬億個癌細胞，很多癌細胞可以通過變異對主幹突變的治療產生免疫。

But what if a therapy targeted two of those basal mutations at the same time? Far fewer cells will have evolved in a way that makes them immune to both forms of attack.

但是如果我們採用一種可以同時治療兩種主幹突變的療法進行治療呢？單個癌細胞成功規避二次靶向藥物交叉攻擊的機會非常罕見。