How cancer cells communicate — and how we can slow them down | Hasini Jayatilaka

譯者: Lilian Chiu 審譯者: SF Huang

Cancer.

癌症。

It's a devastating disease that takes an enormous emotional toll.

它是種讓人身心交瘁的致命疾病。

Not only on the patient, but the patient's loved ones, as well.

不只對病人如此， 對病人的至親亦是如此。

It is a battle that the human race has been fighting for centuries.

人類這場仗已經打了數個世紀。

And while we've made some advancements,

雖然我們有一些進展，

we still haven't beaten it.

但我們仍未打敗癌症。

Two out of five people in the US will develop cancer in their lifetime.

在美國人的一生當中，每 5 人 就會有 2 人得到癌症。

Of those, 90 percent will succumb to the disease due to metastases.

而 90% 的癌症病人 會死於癌細胞轉移。

Metastasis is a spread of cancer from a primary site to a distal site,

轉移就是癌細胞透過循環或淋巴系統

through the circulatory or the lymphatic system.

從原發部位擴散到遠端部位。

For instance, a female patient with breast cancer

比如，一位乳癌的女性病人

doesn't succumb to the disease simply because she has a mass on her breast.

不會只因她的胸部有腫塊就不治。

She succumbs to the disease because it spreads

她致命的原因是癌症擴散到

to the lungs, liver, lymph nodes, brain, bone,

她的肺、肝、淋巴結、大腦和骨頭，

where it becomes unresectable or untreatable.

而這些地方是無法切除 或無法進行治療的。

Metastasis is a complicated process.

轉移是個複雜的過程。

One that I've studied for several years now.

我已經花了數年的時間研究它。

And something that my team and I discovered recently

最近我和我的團隊有個發現，

was that cancer cells are able to communicate with each other

我們發現癌細胞能夠相互溝通

and coordinate their movement,

並協調彼此間的移動，

based on how closely packed they are in the tumor microenvironment.

而這是根據它們在 腫瘤微環境當中的密集程度。

They communicate with each other through two signaling molecules

它們透過兩種訊號分子來彼此溝通：

called Interleukin-6 and Interleukin-8.

介白素 6 和介白素 8。

Now, like anything else in nature,

就像大自然的萬物一樣，

when things get a little too tight, the signal is enhanced,

當太緊密的時候，訊號就會增強，

causing the cancer cells to move away faster from the primary site

造成癌細胞更快速地遠離原發部位，

and spread to a new site.

擴散到新的部位。

So, if we block this signal, using a drug cocktail that we developed,

所以，如果能運用我們開發出的 藥物雞尾酒療法來阻絕這個訊號，

we can stop the communication between cancer cells

我們就能阻擋癌細胞間的溝通，

and slow down the spread of cancer.

減緩癌症的擴散。

Let me pause here for a second

讓我先在這裡暫停一下，

and take you back to when this all began for me in 2010,

帶大家回到這一切初始的 2010 年，

when I was just a sophomore in college.

當時我還只是個大二生。

I had just started working in Dr Danny Wirtz's lab

才剛開始在約翰．霍普金斯大學的

at Johns Hopkins University.

丹尼斯．沃茲博士的實驗室工作，

And I'll be honest: I was a young, naive, Sri Lankan girl,

老實說，我當時是個 年輕天真的斯里蘭卡女孩，

(Laughter)

（笑聲）

who had no previous research experience.

以前沒有任何研究經驗。

And I was tasked to look at how cancer cells move

我接到的任務是要觀察癌細胞

在立體第一型膠原蛋白基質的 培養皿中

in a 3D collagen I matrix

that recapsulated, in a dish,

是如何移動的，

the conditions that cancer cells are exposed to in our bodies.

它模擬了癌細胞在人體內的環境。

This was new and exciting for me,

我覺得既新奇又興奮，

because previous work had been done on 2D, flat, plastic dishes

因為以前研究用的是平面的塑膠皿，

that really weren't representative

它其實無法真正代表

of what the cancer cells are exposed to in our bodies.

癌細胞在我們體內的真實狀況。

Because, let's face it,

因為，咱們要面對現實，

the cancer cells in our bodies aren't stuck onto plastic dishes.

我們體內的癌細胞 並非像在塑膠皿中是固定著的。

It was during this time that I attended a seminar

這段時間我參加了一場研討會，

conducted by Dr Bonnie Bassler from Princeton University,

主講人是普林斯頓大學的 邦尼．巴斯勒博士，

where she talked about how bacteria cells communicate with each other,

她談到細菌細胞如何依據

群體密度所對應的特定行為 來進行彼此的交流。

based on their population density, and perform a specific action.

It was at this moment that a light bulb went off in my head, and I thought,

這一刻我靈光乍現，心想：

"Wow, I see this in my cancer cells every day,

「哇，我每天觀察癌細胞的移動

when it comes to their movement."

也出現這種狀況。」

The idea for my project was thus born.

從而醞釀出我研究計畫的構想。

I hypothesized that cancer cells are able to communicate with each other

我假設癌細胞能夠彼此溝通

and coordinate their movement,

並協調相互間的移動，

based on how closely packed they are in the tumor microenvironment.

依據的資訊是它們在 腫瘤微環境中的密集程度。

I became obsessed with pursuing this hypothesis.

我一頭栽入研究這個假設的可能性。

And fortunately, I work for someone

幸運的是，我的指導教授

who is open to running with my crazy ideas.

以開放的心態來接納我的瘋狂點子。

So, I threw myself into this project.

所以，我就投入了這個專案計畫。

However, I couldn't do it by myself.

然而，我無法獨自完成。

I needed help.

我需要協助。

I definitely needed help.

我肯定需要協助。

So we recruited undergraduate students, graduate students,

所以我們招募了大學生、研究生、

postdoctoral fellows and professors

博士後研究員以及教授，

from different institutions and multiple disciplines

他們來自不同的機構、多個科系，

to come together and work on this idea

集合在一起研究

that I conceived as a sophomore in college.

我在大二時萌生的這個想法。

After years of conducting experiments together

我們一起做了數年的實驗，

and merging different ideas and perspectives,

融合了不同的想法與觀點，

we discovered a new signaling pathway

我們發現了一條新的訊號傳遞路徑，

that controls how cancer cells communicate with each other and move,

它是藉由癌細胞的密度，

來控制彼此間的溝通及移動。

based on their cell density.

Some of you might have heard this,

在座有些人可能有聽過，

because most of social media knows it as the Hasini effect.

因為大部分的社群媒體 把它稱為是「哈西妮效應」。

(Laughter)

（笑聲）

(Applause)

（掌聲）

And we weren't done yet.

我們還沒結束。

We then decided that we wanted to block this signaling pathway

接著，我們決定要阻擋 這條訊號傳遞路徑，

and see if we could slow down the spread of cancer.

看看是否能藉此減緩癌細胞的擴散。

Which we did, in preclinical animal models.

結果，在臨床前動物模型中 的確是如此。

We came up with a drug cocktail consisting of tocilizumab,

我們提出了一種藥物雞尾酒療法 其中包含安挺樂

which is currently used to treat rheumatoid arthritis,

它目前用來治療類風濕性關節炎，

and reparixin, which is currently in clinical trials against breast cancer.

還有 reparixin，它對抗乳癌的 療效目前尚在臨床試驗階段。

And interestingly, what we found was that this cocktail of drugs

有趣的是，我們發現的 這種藥物雞尾酒療法

really had no effect on tumor growth,

其實無法抑制腫瘤的成長，

but directly targeted metastases.

但卻能直接對付癌細胞的轉移。

This was a significant finding,

這是個重大的發現，

because currently, there aren't any FDA-approved therapeutics

因為目前食品及藥物管理局 尚未核准任何

that directly target the spread of cancer.

直接針對癌細胞擴散的治療法。

In fact, the spread of cancer, metastasis,

事實上，癌細胞的擴散也就是轉移，

is thought of as a byproduct of tumor growth.

被認為是伴著腫瘤成長而來的。

Where the idea is, if we can stop the tumor from growing,

所以會有如果阻止腫瘤成長，

we can stop the tumor from spreading.

我們就能阻止腫瘤擴散的想法。

However, most of us know that this is not true.

然而，我們大部分人都知道， 事實並非如此。

We, on the other hand, came up with the drug cocktail

另一方面，我們提出了 這種藥物雞尾酒療法，

that targets metastasis not by targeting tumor growth,

它對付轉移的方式並不是 把目標放在阻止腫瘤成長上，

but by targeting the complex mechanisms that govern it,

而是把目標放在 控制轉移的複雜機制上，

through the targeting of the Hasini effect.

透過處理哈西妮效應來達成。

(Laughter)

（笑聲）

This work was recently published in "Nature Communications,"

最近，這項研究已經在 《自然通訊》期刊中刊出，

and my team and I received an overwhelming response from around the world.

我和我的團隊得到非常多 來自全世界的回應。

Nobody on my team could have predicted this sort of response.

我的團隊中沒有任何人 預期到這樣的反應。

We seem to have struck a nerve.

我們似乎戳到要害了。

Looking back, I am extremely grateful for the positive response that I received,

現在回頭來看，我非常感謝 我所收到的正面回饋，

not only from academia, but also patients,

不只是來自學術界，也來自病人，

and people around the world affected by this terrible disease.

還有全世界被這可怕的 疾病所影響到的人。

As I reflect on this success I've encountered with the Hasini effect,

當我反思在哈西妮效應上 所獲得的成就時，

I keep coming back to the people that I was fortunate enough to work with.

會一直想到我有幸共事過的那些人。

The undergraduate students

那些大學生

who demonstrated superhuman powers through their hard work and dedication.

認真努力和專注奉獻， 展現了他們超凡的能力。

The graduate students and the postdoctoral fellows,

研究生和博士後研究員

my fellow Avengers, who taught me new techniques

我的復仇者聯盟隊友， 他們教會我新的技巧

and always made sure I stayed on track.

且總是確保我沒有偏離正軌。

The professors, my Yodas and my Obi-Wan Kenobis,

教授們是我的尤達和歐比王，

who brought their expertise into making this work into what it is today.

他們挹注自己的專業智識 才讓這項研究有了現今的成果。

The support staff, the friends and family,

支援人員，包括朋友和家人，

people who lifted our spirits,

他們鼓舞我們的士氣，

and never let us give up on our ambitious endeavors.

不許我們放棄這偉大的使命。

The best kind of sidekicks we could have asked for.

沒有比他們更好的伙伴了。

It took a village to help me study metastasis.

有一整個團隊在協助我研究 癌細胞的轉移。

And believe me, without my village, I wouldn't be here.

相信我，若沒有他們， 我今天就不會站在這裡。

Today, our team has grown,

現今，我的團隊已經成長了，

and we are using the Hasini effect to develop combination therapies

我們用哈西妮效應 所發展出的合併療法，

that will effectively target tumor growth and metastases.

將能有效地阻止腫瘤的成長和轉移。

We are engineering new anticancer therapeutics,

我們在研發新的抗癌療法，

to limit toxicity and to reduce drug resistance.

來限制毒性和減低抗藥性。

And we are developing groundbreaking systems

我們正發展開創性的系統，

that will help for the development of better human clinical trials.

以便進行更好的人體臨床試驗。

It blows my mind to think that all this,

光想到這些就讓我很興奮，

the incredible work that I'm pursuing --

我所進行的這項不可思議的研究——

and the fact that I'm standing here, talking to you today --

以及我現在站在這裡對各位演說——

all came from this tiny idea

這些都來自一個小小的點子，

that I had when I was sitting at the back of a seminar

是我坐在研討會中想出來的，

when I was just 20 years old.

而且當年我才二十歲。

I recognize that right now, I am on this incredible journey

意識到自己正走在 這不可思議的旅途上，

that allows me to pursue work that I am extremely passionate about,

我得以去追求我非常熱切 想要去做的研究，

and something that feeds my curiosity on a daily basis.

每天我的好奇心都能得到滿足。

But I have to say, my favorite part of all of this --

但我必須要說，我最喜歡的部分——

other than, of course, being here, talking to you, today --

當然，除了今天站在這裡 和各位分享外——

is the fact that I get to work with a diverse group of people,

就是我能和各式各樣的人共事，

who make my work stronger, better and just so much more fun.

他們讓我的研究更穩固健全、 更好且更有趣。

And because of this, I have to say

因此，我得說，

that collaboration is my favorite superhuman power.

我最喜歡的超能力就是「合作」。

And what I love about this power is that it's not unique to me.

我會愛這項能力是因為 它並非是我獨有的。

It's within all of us.

它存在我們每個人的內在。

My work shows that even cancer cells

我的研究顯示，即使是癌細胞

use collaboration to invade our bodies and spread their wrath.

也會彼此合作來侵襲我們的身體， 散播它們的怒行。

For us humans, it is a superpower that has produced incredible discoveries

對我們人類來說，它是種超能力， 且已經在醫學和科學領域中

in the medical and scientific field.

帶來了許多了不起的發現。

And it is the superpower that we can all turn to

我們都可以使用這種超能力

to inspire us to create something bigger than ourselves,

鼓舞自身創造出超越自我的東西，

that will help make the world a better place.

讓世界變得更好。

Collaboration is the superpower that I turn to, to help me fight cancer.

我採用「合作」這項超能力 協助我對抗癌症。

And I am confident that with the right collaborations,

我有信心，如能妥適地合作，

we will beat this terrible disease.

我們將能夠打敗這可怕的疾病。

Thank you.

謝謝。

(Applause)

（掌聲）