A new superweapon in the fight against cancer | Paula Hammond

Prevodilac: Ivana Krivokuća Lektor: Tijana Mihajlović

Cancer affects all of us --

Rak pogađa sve nas,

especially the ones that come back over and over again,

naročito njegove vrste koje se vraćaju iznova i iznova,

the highly invasive and drug-resistant ones,

one koje su izuzetno invazivne i otporne na lekove,

the ones that defy medical treatment,

koje se opiru medicinskom lečenju,

even when we throw our best drugs at them.

čak i kada ih napadamo najboljim lekovima.

Engineering at the molecular level,

Inženjering na molekularnom nivou,

working at the smallest of scales,

rad na najmanjem mogućem nivou

can provide exciting new ways

može pružiti uzbudljive nove načine

to fight the most aggressive forms of cancer.

za borbu usmerenu protiv najagresivnijih oblika raka.

Cancer is a very clever disease.

Rak je vrlo snalažljiva bolest.

There are some forms of cancer,

Postoje neki oblici raka za koje smo, srećom,

which, fortunately, we've learned how to address relatively well

relativno dobro naučili kako da se postaramo

with known and established drugs and surgery.

poznatim i potvrđenim lekovima i operacijama.

But there are some forms of cancer

Međutim, postoje neke vrste raka

that don't respond to these approaches,

koje ne reaguju na te pristupe

and the tumor survives or comes back,

i tumor preživi ili se vrati,

even after an onslaught of drugs.

čak i nakon snažnog napada lekovima.

We can think of these very aggressive forms of cancer

Možemo da zamislimo te vrlo agresivne oblike raka

as kind of supervillains in a comic book.

kao superzlikovce u stripovima.

They're clever, they're adaptable,

Pametni su, prilagodljivi

and they're very good at staying alive.

i vrlo uspešni u preživljavanju.

And, like most supervillains these days,

Takođe, kao i kod većine superzlikovaca u poslednje vreme,

their superpowers come from a genetic mutation.

njihove supermoći proističu iz genetske mutacije.

The genes that are modified inside these tumor cells

Geni koji su izmenjeni unutar ćelija tumora

can enable and encode for new and unimagined modes of survival,

mogu da osposobe i pronađu ključ za nove nezamislive vidove preživljavanja,

allowing the cancer cell to live through

omogućavajući ćelijama raka da prežive

even our best chemotherapy treatments.

čak i naša najbolja lečenja hemoterapijom.

One example is a trick in which a gene allows a cell,

Jedan od primera je trik u kome gen omogućava da ćelija,

even as the drug approaches the cell,

čak i dok se lek približava ćeliji,

to push the drug out,

istisne lek,

before the drug can have any effect.

pre nego što on može ostvariti dejstvo.

Imagine -- the cell effectively spits out the drug.

Zamislite, ćelija efikasno odbacuje lek.

This is just one example of the many genetic tricks

Ovo je samo jedan primer od mnogo genetskih trikova

in the bag of our supervillain, cancer.

u vreći našeg superzlikovca, raka.

All due to mutant genes.

Sve to je zahvaljujući mutantskim genima.

So, we have a supervillain with incredible superpowers.

Dakle, imamo superzlikovca sa neverovatnim supermoćima.

And we need a new and powerful mode of attack.

Potreban nam je nov i snažan način napada.

Actually, we can turn off a gene.

Zapravo, možemo isključiti gen.

The key is a set of molecules known as siRNA.

Ključ je grupa molekula poznata kao siRNK.

siRNA are short sequences of genetic code

Ona predstavlja kratke nizove genetskog koda

that guide a cell to block a certain gene.

koji dovode do toga da ćelija blokira određeni gen.

Each siRNA molecule can turn off a specific gene

Svaki siRNK molekul može da isključi određeni gen

inside the cell.

unutar ćelije.

For many years since its discovery,

Mnogo godina od njenog otkrića,

scientists have been very excited

naučnici su bili veoma uzbuđeni

about how we can apply these gene blockers in medicine.

zbog načina na koje možemo primeniti te blokatore gena u medicini.

But, there is a problem.

Međutim, postoji problem.

siRNA works well inside the cell.

Molekul siRNK dobro funkcioniše unutar ćelije,

But if it gets exposed to the enzymes

ali kada je izložen enzimima

that reside in our bloodstream or our tissues,

koji se nalaze u našem krvotoku ili našim tkivima,

it degrades within seconds.

razgrađuje se za nekoliko sekundi.

It has to be packaged, protected through its journey through the body

Mora da se upakuje i zaštiti tokom svog putovanja kroz telo,

on its way to the final target inside the cancer cell.

na svom putu ka krajnjoj meti unutar ćelije raka.

So, here's our strategy.

Dakle, evo naše strategije.

First, we'll dose the cancer cell with siRNA, the gene blocker,

Najpre ćeliji raka damo dozu siRNK-a, blokatora gena,

i zaustavimo te gene za preživljavanje,

and silence those survival genes,

and then we'll whop it with a chemo drug.

a zatim je dotučemo hemoterapijom.

But how do we carry that out?

Kako da to sprovedemo?

Using molecular engineering,

Pomoću molekularnog inženjeringa,

we can actually design a superweapon

možemo konstruisati superoružje

that can travel through the bloodstream.

koje može da putuje kroz krvotok.

It has to be tiny enough to get through the bloodstream,

Mora da bude dovoljno malo da prođe kroz krvotok,

it's got to be small enough to penetrate the tumor tissue,

dovoljno malo da prodre u tkivo tumora

and it's got to be tiny enough to be taken up inside the cancer cell.

i mora da bude dovoljno malo da ga ćelija raka može preuzeti u sebe.

To do this job well,

Da bi dobro obavila zadatak,

it has to be about one one-hundredth the size of a human hair.

mora otprilike biti veličine stotog dela ljudske dlake.

Let's take a closer look at how we can build this nanoparticle.

Hajde da bliže pogledamo kako možemo da sačinimo ovu nanočesticu.

First, let's start with the nanoparticle core.

Prvo, započnimo jezgrom nanočestice.

It's a tiny capsule that contains the chemotherapy drug.

To je malena kapsula koja sadrži lek hemoterapije.

This is the poison that will actually end the tumor cell's life.

To je otrov koji će okončati život ćelije tumora.

Around this core, we'll wrap a very thin,

Oko tog jezgra obmotaćemo vrlo tanak,

nanometers-thin blanket of siRNA.

nekoliko nanometara tanak prekrivač molekula siRNK.

This is our gene blocker.

To je naš blokator gena.

Because siRNA is strongly negatively charged,

Zato što je siRNK jako negativno naelektrisan,

we can protect it

možemo ga zaštititi

with a nice, protective layer of positively charged polymer.

finim zaštitnim slojem pozitivno naelektrisanog polimera.

The two oppositely charged molecules stick together

Dva suprotno naelektrisana molekula se priljube zajedno

through charge attraction,

pomoću privlačenja naboja,

and that provides us with a protective layer

a to nam obezbeđuje zaštitni sloj

that prevents the siRNA from degrading in the bloodstream.

koji sprečava da se siRNK razgradi u krvotoku.

We're almost done.

Skoro da smo završili.

(Laughter)

(Smeh)

But there is one more big obstacle we have to think about.

Ipak, postoji još jedna velika prepreka o kojoj moramo da mislimo.

In fact, it may be the biggest obstacle of all.

Zapravo, to je možda najveća prepreka od svih.

How do we deploy this superweapon?

Kako da primenimo ovo superoružje?

I mean, every good weapon needs to be targeted,

Mislim, svako dobro oružje mora da ima metu,

we have to target this superweapon to the supervillain cells

moramo da naciljamo to superoružje ka ćelijama superzlikovca

that reside in the tumor.

koje se nalaze u tumoru.

But our bodies have a natural immune-defense system:

Međutim, naše telo ima prirodni imuni sistem za obranu,

cells that reside in the bloodstream

ćelije koje postoje u krvotoku

and pick out things that don't belong,

i prepoznaju šta tu ne pripada,

so that it can destroy or eliminate them.

tako da to mogu da unište ili uklone.

And guess what? Our nanoparticle is considered a foreign object.

Pogodite šta? Naša nanočestica se smatra stranim telom.

We have to sneak our nanoparticle past the tumor defense system.

Moramo da prokrijumčarimo nanočesticu pored sistema odbrane tumora.

We have to get it past this mechanism of getting rid of the foreign object

Moramo da je dovedemo krišom od ovog mehanizma uklanjanja stranih tela

by disguising it.

tako što ćemo je maskirati.

So we add one more negatively charged layer

Zato dodajemo još jedan sloj negativnog naboja

around this nanoparticle,

oko te nanočestice,

which serves two purposes.

što ima dve svrhe.

First, this outer layer is one of the naturally charged,

Prvo, taj spoljašnji sloj je jedan od prirodno naelektrisanih,

highly hydrated polysaccharides that resides in our body.

visoko hidriranih polisaharida koji postoje u našem telu.

It creates a cloud of water molecules around the nanoparticle

On stvara oblak molekula vode oko nanočestice,

that gives us an invisibility cloaking effect.

što nam daje efekat nevidljivog zastora.

This invisibility cloak allows the nanoparticle

Nevidljivi zastor omogućava nanočestici

to travel through the bloodstream

da putuje kroz krvotok

long and far enough to reach the tumor,

dovoljno dugo i daleko da stigne do tumora,

without getting eliminated by the body.

a da je telo ne ukloni.

Second, this layer contains molecules

Drugo, ovaj sloj sadrži molekule

which bind specifically to our tumor cell.

koji se posebno vezuju za ćeliju tumora.

Once bound, the cancer cell takes up the nanoparticle,

Kada se jednom vežu, ćelija raka preuzima nanočesticu

and now we have our nanoparticle inside the cancer cell

i sada imamo nanočesticu unutar ćelije raka

and ready to deploy.

i spremnu da se aktivira.

Alright! I feel the same way. Let's go!

To! I ja se isto tako osećam. Hajdemo!

(Applause)

(Aplauz)

The siRNA is deployed first.

Molekul siRNK nastupa prvi.

It acts for hours,

Deluje satima,

giving enough time to silence and block those survival genes.

dajući dovoljno vremena da se zaustave i blokiraju ti geni za preživljavanje.

We have now disabled those genetic superpowers.

Sada smo onesposobili te genetske supermoći.

What remains is a cancer cell with no special defenses.

Ono što ostaje je ćelija raka bez naročitih odbrana.

Then, the chemotherapy drug comes out of the core

Tada hemoterapijski lek izlazi iz jezgra

and destroys the tumor cell cleanly and efficiently.

i uništava ćeliju tumora čisto i efikasno.

With sufficient gene blockers,

Sa dovoljno blokatora gena,

we can address many different kinds of mutations,

možemo se pobrinuti za mnogo različitih vrsta mutacija,

allowing the chance to sweep out tumors,

što bi dalo šansu da oteramo tumore,

without leaving behind any bad guys.

bez ostavljanja negativaca.

So, how does our strategy work?

Pa, kako naša strategija funkcioniše?

We've tested these nanostructure particles in animals

Testirali smo na životinjama ove nanočestice

using a highly aggressive form of triple-negative breast cancer.

koristeći izrazito agresivnu vrstu trostruko negativnog raka dojke.

This triple-negative breast cancer exhibits the gene

Trostruko negativni rak dojke pokazuje gen

that spits out cancer drug as soon as it is delivered.

koji izbacuje lek protiv raka čim se on unese.

Usually, doxorubicin -- let's call it "dox" -- is the cancer drug

Obično je doksorubicin - zvaćemo ga doks -

lek protiv raka koji čini prvu liniju lečenja kod raka dojke.

that is the first line of treatment for breast cancer.

So, we first treated our animals with a dox core, dox only.

Dakle, prvo smo lečili životinje jezgrom doksa, samo doksom.

The tumor slowed their rate of growth,

Tempo rasta tumora je usporio,

but they still grew rapidly,

ali i dalje su brzo rasli,

doubling in size over a period of two weeks.

udvostručivši se tokom perioda od dve nedelje.

Then, we tried our combination superweapon.

Zatim smo probali naše kombinovano superoružje.

A nanolayer particle with siRNA against the chemo pump,

Čestica nanosloja sa siRNK-om naspram pumpe za hemoterapiju,

plus, we have the dox in the core.

a pored toga imamo i doks u jezgru.

And look -- we found that not only did the tumors stop growing,

Pogledajte, otkrili smo ne samo da su tumori prestali da rastu,

they actually decreased in size

već su se zapravo smanjili

and were eliminated in some cases.

i bili uklonjeni u nekim slučajevima.

The tumors were actually regressing.

Tumori su se zaista povlačili.

(Applause)

(Aplauz)

What's great about this approach is that it can be personalized.

Sjajna stvar u vezi sa ovim pristupom jeste to da može biti personalizovan.

We can add many different layers of siRNA

Možemo dodati više različitih slojeva siRNK-a

to address different mutations and tumor defense mechanisms.

da bismo se usmerili na različite mutacije i mehanizme odbrane tumora.

And we can put different drugs into the nanoparticle core.

Možemo staviti i različite lekove u središte nanočestice.

As doctors learn how to test patients

Kako doktori budu saznavali kako da testiraju pacijente

and understand certain tumor genetic types,

i shvatali određene genetske tipove tumora,

they can help us determine which patients can benefit from this strategy

mogu nam pomoći da odredimo

kojim pacijentima može koristiti ova strategija

and which gene blockers we can use.

i koje blokatore gena možemo da koristimo.

Ovarian cancer strikes a special chord with me.

Rak jajnika me posebno dira u žicu.

It is a very aggressive cancer,

To je vrlo agresivan rak,

in part because it's discovered at very late stages,

delom zato što se otkriva u vrlo kasnim fazama,

when it's highly advanced

kada je dosta napredovao

and there are a number of genetic mutations.

i postoji veliki broj genetskih mutacija.

After the first round of chemotherapy,

Nakon prve ture hemoterapije,

this cancer comes back for 75 percent of patients.

rak se vraća kod 75 odsto pacijenata

And it usually comes back in a drug-resistant form.

i obično se vraća u obliku koji je otporan na lekove.

High-grade ovarian cancer

Rak jajnika visokog stepena

is one of the biggest supervillains out there.

je jedan od najvećih superzlikovaca.

And we're now directing our superweapon

Sada usmeravamo naše superoružje

toward its defeat.

ka njegovom porazu.

As a researcher,

Kao istraživač,

I usually don't get to work with patients.

obično nemam priliku da radim sa pacijentima.

But I recently met a mother

Ipak, nedavno sam upoznala majku

who is an ovarian cancer survivor, Mimi, and her daughter, Paige.

koja je preživela rak jajnika, Mimi, kao i njenu ćerku Pejdž.

I was deeply inspired by the optimism and strength

Duboko me je inspirisao optimizam i snaga

that both mother and daughter displayed

koje su ispoljile majka i ćerka,

and by their story of courage and support.

kao i njihova priča hrabrosti i podrške.

At this event, we spoke about the different technologies

Na tom događaju smo govorili o različitim tehnologijama

directed at cancer.

usmerenim protiv raka.

And Mimi was in tears

Mimi je bila u suzama

as she explained how learning about these efforts

dok je objašnjavala kako joj saznanje o ovim nastojanjima

gives her hope for future generations,

daje nadu za buduće generacije,

including her own daughter.

uključujući njenu ćerku.

This really touched me.

To me je zaista dirnulo.

It's not just about building really elegant science.

Ne radi se samo o izgradnji veoma elegantne nauke.

It's about changing people's lives.

Radi se o menjanju života ljudi.

It's about understanding the power of engineering

Radi se o razumevanju moći inženjeringa

on the scale of molecules.

na molekularnom nivou.

I know that as students like Paige move forward in their careers,

Znam da će, dok studenti poput Pejdž budu napredovali u svojim karijerama,

they'll open new possibilities

otvoriti nove mogućnosti za bavljenje

in addressing some of the big health problems in the world --

nekim od velikih svetskih problema u oblasti zdravlja,

including ovarian cancer, neurological disorders, infectious disease --

uključujući rak jajnika, neurološka oboljenja, infektivne bolesti,

just as chemical engineering has found a way to open doors for me,

baš kao što je hemijski inženjering našao način da meni otvori vrata

and has provided a way of engineering

i pružio način inženjeringa

on the tiniest scale, that of molecules,

na najsitnijem, molekularnom nivou,

to heal on the human scale.

da bi doneo isceljenje na ljudskom nivou.

Thank you.

Hvala.

(Applause)

(Aplauz)