癌细胞是如何交流的&我们怎样让它们减速

癌细胞是如何交流的&我们怎样让它们减速
How cancer cells communicate — and how we can slow them down | Hasini Jayatilaka

癌症
Cancer.
是一种毁灭性的疾病 会大量消耗人的精神
It’s a devastating diseasethat takes an enormous emotional toll.
不仅是对病人
Not only on the patient,
对病人的至亲而言同样如此
but the patient’s loved ones, as well.
这一场仗 人类已经打了好几个世纪了
It is a battle that the human race has been fighting for centuries.
虽然其中我们也取得了一些进展
And while we’ve made some advancements,
但我们仍然没能攻克它在美国
we still haven’t beaten it.
每五个人里就会有两个在一生中患上癌症
Two out of five people in the US will develop cancer in their lifetime.
而在这些癌症患者中 90%是死于癌细胞转移
Of those, 90 percent will succumb to the disease due to metastases.
转移是指癌细胞通过循环系统
Metastasis is a spread of cancer
或淋巴系统
from a primary site to a distal site,
由原发灶扩散到了远处的转移灶比方说
through the circulatoryor the lymphatic system.
一名女性患者得了乳腺癌
For instance, a female patientwith breast cancer
不会仅仅因为她的
doesn’t succumb to the disease simply
乳房有肿块而死亡
because she has a mass on her breast.
她死亡的原因是这个疾病
She succumbs to the diseasebecause it spreads
扩散到了她的肺部 肝脏 淋巴结 大脑和骨头中
to the lungs, liver,lymph nodes, brain, bone,
而这些地方让癌细胞变得很难对付
where it becomes unresectableor untreatable.
无法治愈 转移是一个很复杂的过程
Metastasis is a complicated process.
我研究这个领域已经很多年了
One that I’ve studiedfor several years now.
最近我和我的团队发现
And something that my teamand I discovered recently
癌细胞之间是可以互相交流
was that cancer cells are ableto communicate with each other
协调彼此之间的移动的
and coordinate their movement,
而这一切是依据他们在肿瘤微环境中的密集程度
based on how closely packed they arein the tumor microenvironment.
它们主要通过两种信号分子彼此交流
They communicate with each otherthrough two signaling molecules
分别是白细胞介素-6和白细胞介素-8
called Interleukin-6 and Interleukin-8. Now,
像自然界里的万物一样
like anything else in nature,
当彼此靠的太紧密了 信号就会增强
when things get a little too tight,the signal is enhanced,
导致癌细胞从原发灶
causing the cancer cells to move away faster
更加快速的转移
from the primary site
扩散到新的部位
and spread to a new site. So,
如果用我们新研发的
if we block this signal,
鸡尾酒药物疗法来屏蔽这种信号
using a drug cocktail that we developed,
就能够阻止癌细胞互相沟通
we can stop the communicationbetween cancer cells
从而降低癌细胞扩散的速度
and slow down the spread of cancer.
让我在此先暂停一会儿
Let me pause here for a second
带各位回到2010年
and take you back to when
这一切开始的时候
this all began for me in 2010,
当时我还是大二的学生
when I was just a sophomore in college.
我刚开始在约翰 · 霍普金斯大学丹尼 · 维尔茨(Danny Wirtz)博士的
I had just started workingin Dr Danny Wirtz’s lab
实验室工作说实话:
at Johns Hopkins University.
我当时还是一个
And I’ll be honest:
年轻稚嫩的斯里兰卡女孩
I was a young, naive, Sri Lankan girl,
(笑声)
(Laughter)
没有任何研究经历
who had no previous research experience.
我的任务是观察癌细胞在一个包裹好的
And I was taskedto look at how cancer cells move
三维的Ⅰ型胶原蛋白培养基里
in a 3D collagen I matrix
是如何移动的
that recapsulated, in a dish,
培养基模拟了癌细胞在我们身体里所接触到的生存环境
the conditions that cancer cellsare exposed to in our bodies.
这对我来说又新鲜又刺激
This was new and exciting for me,
因为我以前只在二维的 扁平的塑料皿里观察过
because previous work had been done on 2D, flat, plastic dishes
而那并不能真正展示出
that really weren’t representative
我们身体里癌细胞存在的样子因为
of what the cancer cellsare exposed to in our bodies. Because,
从现实的角度说
let’s face it,
我们身体里的癌细胞可不是粘在塑料皿上的
the cancer cells in our bodiesaren’t stuck onto plastic dishes.
正是在这段期间 我参加了一个研讨会
It was during this timethat I attended a seminar
演讲人是普林斯顿大学的邦尼 · 巴斯勒( Bonnie Bassler)博士
conducted by Dr Bonnie Basslerfrom Princeton University,
她在会上谈及了细菌的细胞是如何彼此相互交流的
where she talked about how bacteria cellscommunicate with each other,
根据细胞的稠密度 从而实施特定的行动
based on their population density,and perform a specific action.
而就在那一瞬间
It was at this moment that a light bulb went
我灵光一闪
off in my head, and I thought, “Wow,
想到 “对哦 这不是我天天都在观察的
I see thisin my cancer cells every day,
癌细胞的运动模式吗?”
when it comes to their movement.”
因此 研究这个课题的想法就此萌生
The idea for my project was thus born.
我假设癌细胞之间
I hypothesized that cancer cells are
能够根据它们在
able to communicate with each other
肿瘤微环境里的密集程度
and coordinate their movement,
协调运动
based on how closely packed they arein the tumor microenvironment.
相互交流我对这个假设越发痴迷
I became obsessed with pursuingthis hypothesis.
所幸的是
And fortunately, I work for someone
我的负责人接受并支持了这个疯狂的想法于是
who is open to runningwith my crazy ideas. So,
我全身心地投入到了这个项目当中
I threw myself into this project. However,
然而我无法独立完成
I couldn’t do it by myself.
我需要帮助
I needed help.
我真的很需要帮助
I definitely needed help.
因此我们招募了一些本科生
So we recruited undergraduatestudents, graduate students,
研究生 博士后
postdoctoral fellows and professors
还有教授来自不同的学院 不同的学科背景
from different institutionsand multiple disciplines
聚集到一起
to come together and work on this idea
来实现这个我在大二时的构想
that I conceivedas a sophomore in college.
在一起合作进行了几年实验
After years of conductingexperiments together
融合了不同的想法和观点后
and merging different ideasand perspectives,
我们发现了一条新的信号通道
we discovered a new signaling pathway
它根据细胞密度 控制着癌细胞之间
that controls how cancer cellscommunicate with each other and move,
如何交流和移动
based on their cell density.
也许你们当中有人听过了
Some of you might have heard this,
因为大多数媒体都将其称为哈希妮效应
because most of social media knows it as the Hasini effect.
(笑声)
(Laughter)
(掌声)
(Applause)
我们的研究没有到此结束
And we weren’t done yet.
然后我们决定试着去屏蔽这条信号通道
We then decided that we wantedto block this signaling pathway
看下是否能够降低癌细胞扩散的速度
and see if we could slow downthe spread of cancer.
在临床试验之前 我们先在动物模型上进行了实验
Which we did, in preclinicalanimal models.
我们提出了一种鸡尾酒药物疗法 里面包含托珠单抗
We came up with a drug cocktailconsisting of tocilizumab,
目前主要用于治疗风湿性关节炎
which is currently used to treatrheumatoid arthritis,
和瑞帕立新 主要用于治疗乳腺癌 目前正处于临床试验阶段
and reparixin, which is currentlyin clinical trials against breast cancer.
有趣的是 我们发现这种鸡尾酒药物治疗法
And interestingly, what we foundwas that this cocktail of drugs
对于抑制肿瘤的生长一点效果都没有
really had no effect on tumor growth,
但针对癌细胞转移却效果显著
but directly targeted metastases.
这是一个重大的发现
This was a significant finding,
因为目前为止 还没有任何疗法是美国食品药品监督管理局经过认证
because currently, there aren’t anyFDA-approved therapeutics
可以直接针对癌细胞扩散的
that directly target the spread of cancer.
事实上 癌症的扩散和转移
In fact, the spread of cancer, metastasis,
通常认为是肿瘤生长所造成的
is thought of as a byproductof tumor growth.
基于这种观点
Where the idea is,
所以如果我们能阻止肿瘤生长
if we can stop the tumor from growing,
那么就能够阻止肿瘤扩散了但是
we can stop the tumor from spreading. However,
我们大多数人都知道这不是真的
most of us knowthat this is not true. We,
另一方面 我们提出的鸡尾酒药物疗法
on the other hand,came up with the drug cocktail
不是用于控制肿瘤的生长 而是针对癌细胞的转移
that targets metastasisnot by targeting tumor growth,
针对这个控制着癌细胞扩散的复杂机制
but by targeting the complexmechanisms that govern it,
让其成为哈希妮效应的作用目标
through the targetingof the Hasini effect.
(笑声)
(Laughter)
这项研究成果最近发表在了《自然通讯》期刊上
This work was recently publishedin”Nature Communications,”
我和团队也因此收到了许多来自世界各地的反馈
and my team and I received an overwhelming response from around the world.
我的团队里没有人预料到反响会如此热烈
Nobody on my team could have predictedthis sort of response.
好像一下子拨动了大众的心弦
We seem to have struck a nerve.
回顾过去 我真的很感激
Looking back, I am extremely grateful
我所收到的那些积极的反馈
for the positive response that I received,
不仅是来自学术界 同样也来自病人
not only from academia, but also patients,
以及世界各地正饱受癌症折磨的人
and people around the worldaffected by this terrible disease.
当我每次
As I reflect
回想起我在哈希妮效应上所取得的成功时
on this success I’ve encountered with the Hasini effect,
我就会不断想起那些
I keep coming back to the people
我有幸共事过的人
that I was fortunate enough to work with.
那些勤勤恳恳 目标坚定 证明了他们有着超凡能力的本科生
The undergraduate students who demonstrated superhuman powers through their hard work and dedication.
研究生 博士后研究人员
The graduate studentsand the postdoctoral fellows,
还有那些教会了我新的技术 确保我始终行走在
my fellow Avengers,who taught me new techniques
正确的道路上的 复仇者队友们
and always made sure I stayed on track.
我的教授 尤达和欧比旺·克诺比
The professors, my Yodasand my Obi-Wan Kenobis,
因为他们的专业知识 才让这篇研究成果有了今天的样子
who brought their expertise into making this work into what it is today.
还有支持我们的同僚 朋友
The support staff, the friends and family,
家人和那些鼓励我们打起精神
people who lifted our spirits,
让我们永远不要放弃这个伟大理想的伙伴
and never let us give upon our ambitious endeavors.
这些都是我曾经得到过最棒的帮助
The best kind of sidekickswe could have asked for.
一整个团队的人在帮助我研究癌细胞转移
It took a village to help mestudy metastasis.
相信我 如果没有这帮队友 我今天就不会站在这儿如今
And believe me, without my village,I wouldn’t be here. Today,
我的团队已经壮大了许多
our team has grown,
而且我们正在把哈希妮效应发展成一种联合疗法
and we are using the Hasini effectto develop combination therapies
让其有效针对肿瘤生长和癌细胞转移
that will effectively targettumor growth and metastases.
我们正在研发一种新的抗癌治疗法
We are engineeringnew anticancer therapeutics,
来限制毒性 和减轻抗药性
to limit toxicity and to reducedrug resistance.
另外 我们正在建立一些开创性的医疗体系
And we are developinggroundbreaking systems
有助于更好的进行人类临床试验
that will help for the developmentof better human clinical trials.
每次一想到这些 想到我正在追求的这份了不起的事业
It blows my mind to think that all this,
我就感到十分激动
the incredible work that I’m pursuing —
还有我今天能够
and the fact that I’m standing here,
站在这里进行演讲——
talking to you today —
全是因为这个微小的念头
all came from this tiny idea
在我20岁时
that I had when I was sitting
坐在研讨会后排
at the back of a seminar
萌生的这个念头
when I was just 20 years old.
我现在意识到 这段不可思议的旅程
I recognize that right now,I am on this incredible journey
让我能够追求我极度
that allows me to pursue work
热爱的工作
that I am extremely passionate about,
每天都能够满足我的好奇心
and something that feedsmy curiosity on a daily basis.
但是我必须得说
But I have to say,
在这段旅程中 我最喜欢的一点
my favorite part of all of this —
——当然除了站在这儿做演讲——
other than, of course, being here,talking to you, today —
是我能够与这么
is the fact that I get to work
多不同的人一起合作
with a diverse group of people,
他们让我的工作更加扎实 更加完善以及充满乐趣
who make my work stronger, better and just so much more fun.
而正因为这点 我必须得说
And because of this, I have to say
合作是我最喜欢的超凡能力
that collaboration is my favoritesuperhuman power.
而我热爱的这种能力
And what I love about this power is
并非是我独有的
that it’s not unique to me.
它潜藏在我们每个人当中
It’s within all of us.
我的工作向大家展示了即使是癌细胞
My work shows that even cancer cells
也会互相合作损害我们的身体健康
use collaboration to invade our bodiesand spread their wrath.
散播他们的愤怒 对于人类而言
For us humans,
正是因为这种超能力 在医学和科学的领域里
it is a superpower that has produced incredible discoveries
才有了这么多了不起的发现
in the medical and scientific field.
而且这是我们所有人都可以求助的超能力
And it is the superpowerthat we can all turn to
激励我们每个人都创造出比我们自身更伟大的事物
to inspire us to createsomething bigger than ourselves,
从而构建一个更美好的地球
that will help makethe world a better place.
合作是我求助的超能力 它帮助我研究如何对抗癌症
Collaboration is the superpower that I turn to, to help me fight cancer.
而且我有信心 正确的合作
And I am confidentthat with the right collaborations,
能让我们打败这些可怕的疾病
we will beat this terrible disease.
谢谢
Thank you.
(掌声)
(Applause)

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