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.
Rak. Razarajuća bolest koja uzima ogroman emotivni danak. Ne samo pacijentima, već i njihovim voljenima. To je bitka koju ljudi vode vekovima. I mada ima izvesnih pomaka, još ga nismo pobedili. Dvoje od petoro ljudi u SAD-u oboli od raka u toku života. Od toga, 90% podlegne bolesti zbog metastaza.
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.
Metastaza je širenje raka sa primarnog na distalno područje, putem krvnog ili limfnog sistema. Na primer, pacijentkinja sa rakom dojke ne podleže bolesti samo jer ima masu na dojci. Podleže bolesti jer se bolest proširila na pluća, jetru, limfne čvorove, mozak, kosti, gde se ne može operisati ili lečiti. Metastaza je komplikovan proces. Proces koji izučavam već nekoliko godina. Moj tim i ja smo nedavno otkrili da ćelije raka mogu međusobno da komuniciraju i koordinišu kretanja, na osnovu toga koliko su zbijene u mikrosredini tumora. Međusobno komuniciraju preko dva signalizirajuća molekula koji se zovu Interleukin-6 i Interleukin-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,
Sad, kao sve ostalo u prirodi, što su međusobno bliže, signal je jači, uzrokujući da kancerogene ćelije brže putuju sa primarne lokacije i šire se na nove. Dakle, ako blokiramo ovaj signal, koristeći koktel lekova koji smo razvili, možemo da zaustavimo komunikaciju između kancerogenih ćelija i da usporimo širenje raka. Da zastanemo ovde na trenutak i vratimo se u 2010. kada je sve ovo započelo, dok sam još bila na drugoj godini koledža. Tek sam počela sa radom u laboratoriji Dr Denija Virca na Univerzitetu Džons Hopkins. Biću iskrena - bila sam mlada, naivna Šrilankanka,
(Laughter)
(Smeh)
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.
bez prethodnog istraživačkog iskustva. Moj zadatak je bio da posmatram kretanje kancerogenih ćelija u 3D kolagen-1 matriksu koji je reprodukovao, u posudi, uslove kojima su kancerogene ćelije izložene u našim telima. Ovo je za mene bilo novo i uzbudljivo, jer je prethodno rađeno na 2D, ravnim, plastičnim posudama, koje nisu verno predstavljale uslove kojima su kancerogene ćelije izložene u našim telima. Jer, budimo realni, ćelije kancera u našim telima nisu zalepljene na plastične posude. Istovremeno sam pohađala seminar koji je vodila Dr Boni Basler sa Prinston Univerziteta, gde je govorila kako ćelije bakterija međusobno komuniciraju, na osnovu gustine populacije, i izvode izvesne radnje.
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.
U tom trenutku mi se upalila lampica, i pomislila sam, "Oho, ovo vidim u mojim ćelijama kancera svakodnevno, kada posmatram njihovo kretanje." I tako je nastala ideja za moj projekat. Postavila sam hipotezu da ćelije kancera mogu međusobno da komuniciraju i koordinišu svoje kretanje, na osnovu toga koliko su gusto zbijene u mikrosredini tumora. Postala sam opsednuta dokazivanjem ove hipoteze. I srećom, radim za nekoga ko je otvoren da sasluša moje lude ideje. I tako sam se bacila na ovaj projekat.
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.
Ipak, nisam mogla da ga uradim sama. Trebala mi je pomoć. Definitivno mi je trebala pomoć. Te smo regrutovali redovne studente, diplomirane studente, doktore nauka i profesore iz raznih institucija i raznovrsnih disciplina da se skupe i sarađuju na ovoj ideji koju sam smislila na drugoj godini koledža.
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.
Nakon godina izvođenja eksperimenata zajedno i sastavljanja različitih ideja i perspektiva, otkrili smo novu signalnu putanju koja kontroliše kako ćelije kancera komuniciraju međusobno i kako se kreću, na osnovu njihove ćelijske gustine. Neki među vama su možda već čuli, jer je u društvenim medijima poznato kao Hasini efekat.
(Laughter)
(Smeh)
(Applause)
(Aplauz)
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.
Ali mi nismo još završili. Odlučili smo potom da želimo da blokiramo ovu signalnu putanju i probamo da usporimo širenje raka. Što smo i uspeli, u pretkliničkim životinjskim modelima. Smislili smo koktel lekova koji se sastoji od tocilizumaba, koji se trenutno koristi za lečenje reumatoidnog artritisa, i repariksina, koji se trenutno klinički ispituje protiv kancera dojke. Zanimljivo je da smo otkrili da ovaj koktel lekova nije imao efekta na rast tumora, ali je direktno ciljao metastaze. Ovo je bilo bitno otkriće, jer trenutno, ne postoji nijedna FDA odobrena terapija koja direktno cilja širenje raka.
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.
Zapravo, širenje raka - metastaze, se smatra sporednim proizvodom rasta tumora. Osnovna zamisao je da, ako možemo da zaustavimo rast tumora, možemo da zaustavimo širenje tumora. Ipak, većina nas zna da ovo nije istina. Mi smo, sa druge strane, osmislili koktel lekova koji cilja metastaze ne ciljajući rast tumora, već ciljajući kompleksne mehanizme kojim se upravlja, ciljanjem Hasini efekta.
(Laughter)
(Smeh)
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.
Ovaj rad je nedavno objavljen u "Komunikacijama prirode". Moj tim i ja smo obasuti brojnim odgovorima sa raznih strana sveta. Niko u mom timu nije mogao predvideti ovakav odgovor. Izgleda da smo udarili pravo u živac. U retrospektivi, ekstremno sam zahvalna za pozitivne odgovore koje sam primila, ne samo od akademika, već i od pacijenata, i ljudi širom sveta koji su pogođeni ovom užasnom bolešću.
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.
Dok razmišljam o uspehu na koji sam naišla sa Hasini efektom, stalno se vraćam na ljude sa kojima sam imala sreće da sarađujem. Redovni studenti koji su pokazali nadljudske moći kroz naporan rad i posvećenost. Diplomirani studenti i doktori nauka, moji partneri Osvetnici, koji su me naučili novim tehnikama i uvek vodili računa da ostanem na pravom putu. Profesori, moje Jode i moji Obii Van Kenobii, koji su svojom ekspertizom doprineli da ovaj rad postane ono što jeste. Pomoćno osoblje, prijatelji i porodica, ljudi koji su nas bodrili, i nisu nikada dozvolili da odustanemo od naših ambicioznih nastojanja. Najbolja podrška koju smo mogli zamisliti. Trebalo je jedno celo selo da mi pomogne u izučavanju metastaza. I verujte mi, bez mog sela, ne bih bila ovde.
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.
Danas, naš tim je narastao, i koristimo Hasini efekat da razvijemo kombinovane terapije koje će efikasno ciljati rast tumora i metastaze. Stvaramo nove antikancerogene terapije, da ograničimo toksičnost i smanjimo otpornost na lekove. I razvijamo revolucionarne sisteme koji će pomoći u razvoju boljih kliničkih ispitivanja na ljudima. Ostajem bez daha kad pomislim da sve ovo, neverovatan rad kojim se bavim - i činjenica da stojim ovde, govorim pred vama danas - sve je nastalo iz ove malene ideje koja mi je sinula u zadnjim redovima na seminaru kada mi je bilo samo 20 godina.
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.
Shvatam sada da sam na neverovatnom putovanju koje mi dopušta da se bavim radom za koji posedujem ogromnu strast, i koji svakodnevno pothranjuje moju radoznalost. Ali moram reći, moj omiljeni deo svega ovog je - sem, naravno, što sam ovde, i govorim pred vama, danas - činjenica da sarađujem sa raznolikom grupom ljudi, koji čine moj rad jačim, boljim i zabavnijim. I zbog toga, moram da kažem da je saradnja moja omiljena nadljudska moć. Volim što nije svojstvena samo meni. Postoji u svima nama.
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.
Moj rad dokazuje da čak i ćelije kancera koriste saradnju da napadnu naša tela i šire svoju srdžbu. Za nas ljude, to je supermoć koja je stvorila neverovatna otkrića u poljima medicine i nauke. I to je supermoć kojoj se svi možemo okrenuti u potrazi za inspiracijom da stvorimo nešto veće od nas samih, što će pomoći da učini svet boljim. Saradnja je supermoć kojoj se priklanjam, da mi pomogne da pobedim rak. I sigurna sam da ćemo uz prave saradnje, pobediti ovu užasnu bolest.
Thank you.
Hvala.
(Applause)
(Aplauz)