Cancer. It's a devastating disease that takes an enormous emotional toll. Not only on the patient, but the patient's loved ones, as well. It is a battle that the human race has been fighting for centuries. And while we've made some advancements, we still haven't beaten it. Two out of five people in the US will develop cancer in their lifetime. Of those, 90 percent will succumb to the disease due to metastases.
癌症。 它是種讓人身心交瘁的致命疾病。 不只對病人如此, 對病人的至親亦是如此。 人類這場仗已經打了數個世紀。 雖然我們有一些進展, 但我們仍未打敗癌症。 在美國人的一生當中,每 5 人 就會有 2 人得到癌症。 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, through the circulatory or the lymphatic system. For instance, a female patient with breast cancer doesn't succumb to the disease simply because she has a mass on her breast. She succumbs to the disease because it spreads to the lungs, liver, lymph nodes, brain, bone, where it becomes unresectable or untreatable. Metastasis is a complicated process. One that I've studied for several years now. And something that my team and I discovered recently was that cancer cells are able to communicate with each other and coordinate their movement, based on how closely packed they are in the tumor microenvironment. They communicate with each other through two signaling molecules called Interleukin-6 and Interleukin-8.
轉移就是癌細胞透過循環或淋巴系統 從原發部位擴散到遠端部位。 比如,一位乳癌的女性病人 不會只因她的胸部有腫塊就不治。 她致命的原因是癌症擴散到 她的肺、肝、淋巴結、大腦和骨頭, 而這些地方是無法切除 或無法進行治療的。 轉移是個複雜的過程。 我已經花了數年的時間研究它。 最近我和我的團隊有個發現, 我們發現癌細胞能夠相互溝通 並協調彼此間的移動, 而這是根據它們在 腫瘤微環境當中的密集程度。 它們透過兩種訊號分子來彼此溝通: 介白素 6 和介白素 8。
Now, like anything else in nature, when things get a little too tight, the signal is enhanced, causing the cancer cells to move away faster from the primary site and spread to a new site. So, if we block this signal, using a drug cocktail that we developed, we can stop the communication between cancer cells and slow down the spread of cancer. Let me pause here for a second and take you back to when this all began for me in 2010, when I was just a sophomore in college. I had just started working in Dr Danny Wirtz's lab at Johns Hopkins University. And I'll be honest: I was a young, naive, Sri Lankan girl,
就像大自然的萬物一樣, 當太緊密的時候,訊號就會增強, 造成癌細胞更快速地遠離原發部位, 擴散到新的部位。 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, 我們就能阻擋癌細胞間的溝通, 減緩癌症的擴散。 讓我先在這裡暫停一下, 帶大家回到這一切初始的 2010 年, 當時我還只是個大二生。 才剛開始在約翰.霍普金斯大學的 丹尼斯.沃茲博士的實驗室工作, 老實說,我當時是個 年輕天真的斯里蘭卡女孩,
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who had no previous research experience. And I was tasked to look at how cancer cells move in a 3D collagen I matrix that recapsulated, in a dish, the conditions that cancer cells are exposed to in our bodies. This was new and exciting for me, because previous work had been done on 2D, flat, plastic dishes that really weren't representative of what the cancer cells are exposed to in our bodies. Because, let's face it, the cancer cells in our bodies aren't stuck onto plastic dishes. It was during this time that I attended a seminar conducted by Dr Bonnie Bassler from Princeton University, where she talked about how bacteria cells communicate with each other, based on their population density, and perform a specific action.
以前沒有任何研究經驗。 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 是如何移動的, 它模擬了癌細胞在人體內的環境。 我覺得既新奇又興奮, 因為以前研究用的是平面的塑膠皿, 它其實無法真正代表 癌細胞在我們體內的真實狀況。 因為,咱們要面對現實, 我們體內的癌細胞 並非像在塑膠皿中是固定著的。 這段時間我參加了一場研討會, 主講人是普林斯頓大學的 邦尼.巴斯勒博士, 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。
It was at this moment that a light bulb went off in my head, and I thought, "Wow, I see this in my cancer cells every day, when it comes to their movement." The idea for my project was thus born. I hypothesized that cancer cells are able to communicate with each other and coordinate their movement, based on how closely packed they are in the tumor microenvironment. I became obsessed with pursuing this hypothesis. And fortunately, I work for someone who is open to running with my crazy ideas. So, I threw myself into this project.
這一刻我靈光乍現,心想: 「哇,我每天觀察癌細胞的移動 也出現這種狀況。」 從而醞釀出我研究計畫的構想。 我假設癌細胞能夠彼此溝通 並協調相互間的移動, 依據的資訊是它們在 腫瘤微環境中的密集程度。 我一頭栽入研究這個假設的可能性。 幸運的是,我的指導教授 以開放的心態來接納我的瘋狂點子。 所以,我就投入了這個專案計畫。
However, I couldn't do it by myself. I needed help. I definitely needed help. So we recruited undergraduate students, graduate students, postdoctoral fellows and professors from different institutions and multiple disciplines to come together and work on this idea that I conceived as a sophomore in college.
然而,我無法獨自完成。 我需要協助。 我肯定需要協助。 所以我們招募了大學生、研究生、 博士後研究員以及教授, 他們來自不同的機構、多個科系, 集合在一起研究 我在大二時萌生的這個想法。
After years of conducting experiments together and merging different ideas and perspectives, we discovered a new signaling pathway that controls how cancer cells communicate with each other and move, based on their cell density. Some of you might have heard this, because most of social media knows it as the Hasini effect.
我們一起做了數年的實驗, 融合了不同的想法與觀點, 我們發現了一條新的訊號傳遞路徑, 它是藉由癌細胞的密度, 來控制彼此間的溝通及移動。 在座有些人可能有聽過, 因為大部分的社群媒體 把它稱為是「哈西妮效應」。
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And we weren't done yet. We then decided that we wanted to block this signaling pathway and see if we could slow down the spread of cancer. Which we did, in preclinical animal models. We came up with a drug cocktail consisting of tocilizumab, which is currently used to treat rheumatoid arthritis, and reparixin, which is currently in clinical trials against breast cancer. And interestingly, what we found was that this cocktail of drugs really had no effect on tumor growth, but directly targeted metastases. This was a significant finding, because currently, there aren't any FDA-approved therapeutics that directly target the spread of cancer.
我們還沒結束。 接著,我們決定要阻擋 這條訊號傳遞路徑, 看看是否能藉此減緩癌細胞的擴散。 結果,在臨床前動物模型中 的確是如此。 我們提出了一種藥物雞尾酒療法 其中包含安挺樂 它目前用來治療類風濕性關節炎, 還有 reparixin,它對抗乳癌的 療效目前尚在臨床試驗階段。 有趣的是,我們發現的 這種藥物雞尾酒療法 其實無法抑制腫瘤的成長, 但卻能直接對付癌細胞的轉移。 這是個重大的發現, 因為目前食品及藥物管理局 尚未核准任何 直接針對癌細胞擴散的治療法。
In fact, the spread of cancer, metastasis, is thought of as a byproduct of tumor growth. Where the idea is, if we can stop the tumor from growing, we can stop the tumor from spreading. However, most of us know that this is not true. We, on the other hand, came up with the drug cocktail that targets metastasis not by targeting tumor growth, but by targeting the complex mechanisms that govern it, through the targeting of the Hasini effect.
事實上,癌細胞的擴散也就是轉移, 被認為是伴著腫瘤成長而來的。 所以會有如果阻止腫瘤成長, 我們就能阻止腫瘤擴散的想法。 然而,我們大部分人都知道, 事實並非如此。 另一方面,我們提出了 這種藥物雞尾酒療法, 它對付轉移的方式並不是 把目標放在阻止腫瘤成長上, 而是把目標放在 控制轉移的複雜機制上, 透過處理哈西妮效應來達成。
(Laughter)
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This work was recently published in "Nature Communications," and my team and I received an overwhelming response from around the world. Nobody on my team could have predicted this sort of response. We seem to have struck a nerve. Looking back, I am extremely grateful for the positive response that I received, not only from academia, but also patients, and people around the world affected by this terrible disease.
最近,這項研究已經在 《自然通訊》期刊中刊出, 我和我的團隊得到非常多 來自全世界的回應。 我的團隊中沒有任何人 預期到這樣的反應。 我們似乎戳到要害了。 現在回頭來看,我非常感謝 我所收到的正面回饋, 不只是來自學術界,也來自病人, 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, I keep coming back to the people that I was fortunate enough to work with. The undergraduate students who demonstrated superhuman powers through their hard work and dedication. The graduate students and the postdoctoral fellows, my fellow Avengers, who taught me new techniques and always made sure I stayed on track. The professors, my Yodas and my Obi-Wan Kenobis, who brought their expertise into making this work into what it is today. The support staff, the friends and family, people who lifted our spirits, and never let us give up on our ambitious endeavors. The best kind of sidekicks we could have asked for. It took a village to help me study metastasis. And believe me, without my village, I wouldn't be here.
當我反思在哈西妮效應上 所獲得的成就時, 會一直想到我有幸共事過的那些人。 那些大學生 認真努力和專注奉獻, 展現了他們超凡的能力。 研究生和博士後研究員 我的復仇者聯盟隊友, 他們教會我新的技巧 且總是確保我沒有偏離正軌。 教授們是我的尤達和歐比王, 他們挹注自己的專業智識 才讓這項研究有了現今的成果。 支援人員,包括朋友和家人, 他們鼓舞我們的士氣, 不許我們放棄這偉大的使命。 沒有比他們更好的伙伴了。 有一整個團隊在協助我研究 癌細胞的轉移。 相信我,若沒有他們, 我今天就不會站在這裡。
Today, our team has grown, and we are using the Hasini effect to develop combination therapies that will effectively target tumor growth and metastases. We are engineering new anticancer therapeutics, to limit toxicity and to reduce drug resistance. And we are developing groundbreaking systems that will help for the development of better human clinical trials. It blows my mind to think that all this, the incredible work that I'm pursuing -- and the fact that I'm standing here, talking to you today -- all came from this tiny idea that I had when I was sitting at the back of a seminar when I was just 20 years old.
現今,我的團隊已經成長了, 我們用哈西妮效應 所發展出的合併療法, 將能有效地阻止腫瘤的成長和轉移。 我們在研發新的抗癌療法, 來限制毒性和減低抗藥性。 我們正發展開創性的系統, 以便進行更好的人體臨床試驗。 光想到這些就讓我很興奮, 我所進行的這項不可思議的研究—— 以及我現在站在這裡對各位演說—— 這些都來自一個小小的點子, 是我坐在研討會中想出來的, 而且當年我才二十歲。
I recognize that right now, I am on this incredible journey that allows me to pursue work that I am extremely passionate about, and something that feeds my curiosity on a daily basis. But I have to say, my favorite part of all of this -- other than, of course, being here, talking to you, today -- is the fact that I get to work with a diverse group of people, who make my work stronger, better and just so much more fun. And because of this, I have to say that collaboration is my favorite superhuman power. And what I love about this power is that it's not unique to me. It's within all of us.
意識到自己正走在 這不可思議的旅途上, 我得以去追求我非常熱切 想要去做的研究, 每天我的好奇心都能得到滿足。 但我必須要說,我最喜歡的部分—— 當然,除了今天站在這裡 和各位分享外—— 就是我能和各式各樣的人共事, 他們讓我的研究更穩固健全、 更好且更有趣。 因此,我得說, 我最喜歡的超能力就是「合作」。 我會愛這項能力是因為 它並非是我獨有的。 它存在我們每個人的內在。
My work shows that even cancer cells use collaboration to invade our bodies and spread their wrath. For us humans, it is a superpower that has produced incredible discoveries in the medical and scientific field. And it is the superpower that we can all turn to to inspire us to create something bigger than ourselves, that will help make the world a better place. Collaboration is the superpower that I turn to, to help me fight cancer. And I am confident that with the right collaborations, we will beat this terrible disease.
我的研究顯示,即使是癌細胞 也會彼此合作來侵襲我們的身體, 散播它們的怒行。 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 帶來了許多了不起的發現。 我們都可以使用這種超能力 鼓舞自身創造出超越自我的東西, 讓世界變得更好。 我採用「合作」這項超能力 協助我對抗癌症。 我有信心,如能妥適地合作, 我們將能夠打敗這可怕的疾病。
Thank you.
謝謝。
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