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

Prevodilac: Milica Costa Lektor: Ivana Korom

Cancer.

Rak.

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

Razarajuća bolest koja uzima ogroman emotivni danak.

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

Ne samo pacijentima, već i njihovim voljenima.

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

To je bitka koju ljudi vode vekovima.

And while we've made some advancements,

I mada ima izvesnih pomaka,

we still haven't beaten it.

još ga nismo pobedili.

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

Dvoje od petoro ljudi u SAD-u oboli od raka u toku života.

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

Od toga, 90% podlegne bolesti zbog metastaza.

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

Metastaza je širenje raka sa primarnog na distalno područje,

through the circulatory or the lymphatic system.

putem krvnog ili limfnog sistema.

For instance, a female patient with breast cancer

Na primer, pacijentkinja sa rakom dojke

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

ne podleže bolesti samo jer ima masu na dojci.

She succumbs to the disease because it spreads

Podleže bolesti jer se bolest proširila

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

na pluća, jetru, limfne čvorove, mozak, kosti,

where it becomes unresectable or untreatable.

gde se ne može operisati ili lečiti.

Metastasis is a complicated process.

Metastaza je komplikovan proces.

One that I've studied for several years now.

Proces koji izučavam već nekoliko godina.

And something that my team and I discovered recently

Moj tim i ja smo nedavno otkrili

was that cancer cells are able to communicate with each other

da ćelije raka mogu međusobno da komuniciraju

and coordinate their movement,

i koordinišu kretanja,

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

na osnovu toga koliko su zbijene u mikrosredini tumora.

They communicate with each other through two signaling molecules

Međusobno komuniciraju preko dva signalizirajuća molekula

called Interleukin-6 and Interleukin-8.

koji se zovu Interleukin-6 i Interleukin-8.

Now, like anything else in nature,

Sad, kao sve ostalo u prirodi,

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

što su međusobno bliže, signal je jači,

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

uzrokujući da kancerogene ćelije brže putuju sa primarne lokacije

and spread to a new site.

i šire se na nove.

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

Dakle, ako blokiramo ovaj signal, koristeći koktel lekova koji smo razvili,

we can stop the communication between cancer cells

možemo da zaustavimo komunikaciju između kancerogenih ćelija

and slow down the spread of cancer.

i da usporimo širenje raka.

Let me pause here for a second

Da zastanemo ovde na trenutak

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

i vratimo se u 2010. kada je sve ovo započelo,

when I was just a sophomore in college.

dok sam još bila na drugoj godini koledža.

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

Tek sam počela sa radom u laboratoriji Dr Denija Virca

at Johns Hopkins University.

na Univerzitetu Džons Hopkins.

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

Biću iskrena - bila sam mlada, naivna Šrilankanka,

(Laughter)

(Smeh)

who had no previous research experience.

bez prethodnog istraživačkog iskustva.

And I was tasked to look at how cancer cells move

Moj zadatak je bio da posmatram kretanje kancerogenih ćelija

in a 3D collagen I matrix

u 3D kolagen-1 matriksu

that recapsulated, in a dish,

koji je reprodukovao, u posudi,

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

uslove kojima su kancerogene ćelije izložene u našim telima.

This was new and exciting for me,

Ovo je za mene bilo novo i uzbudljivo,

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

jer je prethodno rađeno na 2D, ravnim, plastičnim posudama,

that really weren't representative

koje nisu verno predstavljale uslove

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

kojima su kancerogene ćelije izložene u našim telima.

Because, let's face it,

Jer, budimo realni,

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

ćelije kancera u našim telima nisu zalepljene na plastične posude.

It was during this time that I attended a seminar

Istovremeno sam pohađala seminar

conducted by Dr Bonnie Bassler from Princeton University,

koji je vodila Dr Boni Basler sa Prinston Univerziteta,

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

gde je govorila kako ćelije bakterija međusobno komuniciraju,

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

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,

U tom trenutku mi se upalila lampica, i pomislila sam,

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

"Oho, ovo vidim u mojim ćelijama kancera svakodnevno,

when it comes to their movement."

kada posmatram njihovo kretanje."

The idea for my project was thus born.

I tako je nastala ideja za moj projekat.

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

Postavila sam hipotezu da ćelije kancera mogu međusobno da komuniciraju

and coordinate their movement,

i koordinišu svoje kretanje,

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

na osnovu toga koliko su gusto zbijene u mikrosredini tumora.

I became obsessed with pursuing this hypothesis.

Postala sam opsednuta dokazivanjem ove hipoteze.

And fortunately, I work for someone

I srećom, radim za nekoga

who is open to running with my crazy ideas.

ko je otvoren da sasluša moje lude ideje.

So, I threw myself into this project.

I tako sam se bacila na ovaj projekat.

However, I couldn't do it by myself.

Ipak, nisam mogla da ga uradim sama.

I needed help.

Trebala mi je pomoć.

I definitely needed help.

Definitivno mi je trebala pomoć.

So we recruited undergraduate students, graduate students,

Te smo regrutovali redovne studente, diplomirane studente,

postdoctoral fellows and professors

doktore nauka i profesore

from different institutions and multiple disciplines

iz raznih institucija i raznovrsnih disciplina

to come together and work on this idea

da se skupe i sarađuju na ovoj ideji

that I conceived as a sophomore in college.

koju sam smislila na drugoj godini koledža.

After years of conducting experiments together

Nakon godina izvođenja eksperimenata zajedno

and merging different ideas and perspectives,

i sastavljanja različitih ideja i perspektiva,

we discovered a new signaling pathway

otkrili smo novu signalnu putanju

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

koja kontroliše kako ćelije kancera komuniciraju međusobno i kako se kreću,

based on their cell density.

na osnovu njihove ćelijske gustine.

Some of you might have heard this,

Neki među vama su možda već čuli,

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

jer je u društvenim medijima poznato kao Hasini efekat.

(Laughter)

(Smeh)

(Applause)

(Aplauz)

And we weren't done yet.

Ali mi nismo još završili.

We then decided that we wanted to block this signaling pathway

Odlučili smo potom da želimo da blokiramo ovu signalnu putanju

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

i probamo da usporimo širenje raka.

Which we did, in preclinical animal models.

Što smo i uspeli, u pretkliničkim životinjskim modelima.

We came up with a drug cocktail consisting of tocilizumab,

Smislili smo koktel lekova koji se sastoji od tocilizumaba,

which is currently used to treat rheumatoid arthritis,

koji se trenutno koristi za lečenje reumatoidnog artritisa,

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

i repariksina, koji se trenutno klinički ispituje protiv kancera dojke.

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

Zanimljivo je da smo otkrili da ovaj koktel lekova

really had no effect on tumor growth,

nije imao efekta na rast tumora,

but directly targeted metastases.

ali je direktno ciljao metastaze.

This was a significant finding,

Ovo je bilo bitno otkriće,

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

jer trenutno, ne postoji nijedna FDA odobrena terapija

that directly target the spread of cancer.

koja direktno cilja širenje raka.

In fact, the spread of cancer, metastasis,

Zapravo, širenje raka - metastaze,

is thought of as a byproduct of tumor growth.

se smatra sporednim proizvodom rasta tumora.

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

Osnovna zamisao je da, ako možemo da zaustavimo rast tumora,

we can stop the tumor from spreading.

možemo da zaustavimo širenje tumora.

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

Ipak, većina nas zna da ovo nije istina.

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

Mi smo, sa druge strane, osmislili koktel lekova

that targets metastasis not by targeting tumor growth,

koji cilja metastaze ne ciljajući rast tumora,

but by targeting the complex mechanisms that govern it,

već ciljajući kompleksne mehanizme kojim se upravlja,

through the targeting of the Hasini effect.

ciljanjem Hasini efekta.

(Laughter)

(Smeh)

This work was recently published in "Nature Communications,"

Ovaj rad je nedavno objavljen u "Komunikacijama prirode".

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

Moj tim i ja smo obasuti brojnim odgovorima sa raznih strana sveta.

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

Niko u mom timu nije mogao predvideti ovakav odgovor.

We seem to have struck a nerve.

Izgleda da smo udarili pravo u živac.

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

U retrospektivi, ekstremno sam zahvalna za pozitivne odgovore koje sam primila,

not only from academia, but also patients,

ne samo od akademika, već i od pacijenata,

and people around the world affected by this terrible disease.

i ljudi širom sveta koji su pogođeni ovom užasnom bolešću.

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

Dok razmišljam o uspehu na koji sam naišla sa Hasini efektom,

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

stalno se vraćam na ljude sa kojima sam imala sreće da sarađujem.

The undergraduate students

Redovni studenti

who demonstrated superhuman powers through their hard work and dedication.

koji su pokazali nadljudske moći kroz naporan rad i posvećenost.

The graduate students and the postdoctoral fellows,

Diplomirani studenti i doktori nauka,

my fellow Avengers, who taught me new techniques

moji partneri Osvetnici, koji su me naučili novim tehnikama

and always made sure I stayed on track.

i uvek vodili računa da ostanem na pravom putu.

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

Profesori, moje Jode i moji Obii Van Kenobii,

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

koji su svojom ekspertizom doprineli da ovaj rad postane ono što jeste.

The support staff, the friends and family,

Pomoćno osoblje, prijatelji i porodica,

people who lifted our spirits,

ljudi koji su nas bodrili,

and never let us give up on our ambitious endeavors.

i nisu nikada dozvolili da odustanemo od naših ambicioznih nastojanja.

The best kind of sidekicks we could have asked for.

Najbolja podrška koju smo mogli zamisliti.

It took a village to help me study metastasis.

Trebalo je jedno celo selo da mi pomogne u izučavanju metastaza.

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

I verujte mi, bez mog sela, ne bih bila ovde.

Today, our team has grown,

Danas, naš tim je narastao,

and we are using the Hasini effect to develop combination therapies

i koristimo Hasini efekat da razvijemo kombinovane terapije

that will effectively target tumor growth and metastases.

koje će efikasno ciljati rast tumora i metastaze.

We are engineering new anticancer therapeutics,

Stvaramo nove antikancerogene terapije,

to limit toxicity and to reduce drug resistance.

da ograničimo toksičnost i smanjimo otpornost na lekove.

And we are developing groundbreaking systems

I razvijamo revolucionarne sisteme

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

koji će pomoći u razvoju boljih kliničkih ispitivanja na ljudima.

It blows my mind to think that all this,

Ostajem bez daha kad pomislim da sve ovo,

the incredible work that I'm pursuing --

neverovatan rad kojim se bavim -

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

i činjenica da stojim ovde, govorim pred vama danas -

all came from this tiny idea

sve je nastalo iz ove malene ideje

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

koja mi je sinula u zadnjim redovima na seminaru

when I was just 20 years old.

kada mi je bilo samo 20 godina.

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

Shvatam sada da sam na neverovatnom putovanju

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

koje mi dopušta da se bavim radom za koji posedujem ogromnu strast,

and something that feeds my curiosity on a daily basis.

i koji svakodnevno pothranjuje moju radoznalost.

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

Ali moram reći, moj omiljeni deo svega ovog je -

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

sem, naravno, što sam ovde, i govorim pred vama, danas -

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

činjenica da sarađujem sa raznolikom grupom ljudi,

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

koji čine moj rad jačim, boljim i zabavnijim.

And because of this, I have to say

I zbog toga, moram da kažem da je

that collaboration is my favorite superhuman power.

saradnja moja omiljena nadljudska moć.

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

Volim što nije svojstvena samo meni.

It's within all of us.

Postoji u svima nama.

My work shows that even cancer cells

Moj rad dokazuje da čak i ćelije kancera

use collaboration to invade our bodies and spread their wrath.

koriste saradnju da napadnu naša tela i šire svoju srdžbu.

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

Za nas ljude, to je supermoć koja je stvorila neverovatna otkrića

in the medical and scientific field.

u poljima medicine i nauke.

And it is the superpower that we can all turn to

I to je supermoć kojoj se svi možemo okrenuti

to inspire us to create something bigger than ourselves,

u potrazi za inspiracijom da stvorimo nešto veće od nas samih,

that will help make the world a better place.

što će pomoći da učini svet boljim.

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

Saradnja je supermoć kojoj se priklanjam, da mi pomogne da pobedim rak.

And I am confident that with the right collaborations,

I sigurna sam da ćemo uz prave saradnje,

we will beat this terrible disease.

pobediti ovu užasnu bolest.

Thank you.

Hvala.

(Applause)

(Aplauz)