Cancer. Many of us have lost family, friends or loved ones to this horrible disease. I know there are some of you in the audience who are cancer survivors, or who are fighting cancer at this moment. My heart goes out to you. While this word often conjures up emotions of sadness and anger and fear, I bring you good news from the front lines of cancer research. The fact is, we are starting to win the war on cancer. In fact, we lie at the intersection of the three of the most exciting developments within cancer research.
Rak. Mnogi od nas izgubili su obitelj, prijatelje ili voljene osobe od ove užasne bolesti. Znam da su neki od vas u publici preživjeli rak, ili se bore s rakom u ovom trenutku. Suosjećam s vama. Iako ova riječ često priziva osjećaje tuge, ljutnje i straha, donosim vam dobre vijesti s prve crte istraživanja raka. Činjenica je da počinjemo pobjeđivati u ratu protiv raka. Zapravo, na raskrižju smo tri najuzbudljivija razvoja unutar istraživanja raka.
The first is cancer genomics. The genome is a composition of all the genetic information encoded by DNA in an organism. In cancers, changes in the DNA called mutations are what drive these cancers to go out of control. Around 10 years ago, I was part of the team at Johns Hopkins that first mapped the mutations of cancers. We did this first for colorectal, breast, pancreatic and brain cancers. And since then, there have been over 90 projects in 70 countries all over the world, working to understand the genetic basis of these diseases. Today, tens of thousands of cancers are understood down to exquisite molecular detail.
Prvi je genomika raka. Genom je sklop svih genetskih informacija kodiranih od strane DNK u organizmu. Kod raka, mutacije u DNK su ono što tjera rak da nekontrolirano raste. Prije 10 godina bio sam dio tima u bolnici Johns Hopkins koji je prvi mapirao mutacije raka. Radili smo prvo s rektalnim, rakom dojke, gušterače i mozga. I od onda bilo je preko 90 projekata u sedamdeset zemalja diljem svijeta, koji rade na tome da razumiju genetske osnove ovih bolesti. Danas razumijemo desetke tisuća pojava raka do nevjerojatnih molekularnih detalja.
The second revolution is precision medicine, also known as "personalized medicine." Instead of one-size-fits-all methods to be able to treat cancers, there is a whole new class of drugs that are able to target cancers based on their unique genetic profile. Today, there are a host of these tailor-made drugs, called targeted therapies, available to physicians even today to be able to personalize their therapy for their patients, and many others are in development.
Druga revolucija je precizna medicina, poznata i kao "personalizirana medicina." Umjesto jedne metode liječenja za sve tipove raka, postoji potpuno nova serija lijekova kojom možemo ciljano liječiti rak, na temelju jedinstvenog genetskog profila. Danas, postoji mnoštvo ovih specijaliziranih lijekova nazvanih ciljane terapije, dostupne liječnicima već danas, kako bi mogli stvoriti osobnu terapiju za svoje pacijente, a mnoge druge se još razvijaju.
The third exciting revolution is immunotherapy, and this is really exciting. Scientists have been able to leverage the immune system in the fight against cancer. For example, there have been ways where we find the off switches of cancer, and new drugs have been able to turn the immune system back on, to be able to fight cancer. In addition, there are ways where you can take away immune cells from the body, train them, engineer them and put them back into the body to fight cancer. Almost sounds like science fiction, doesn't it?
Treća uzbudljiva revolucija je imunoterapija, i to je zaista uzbudljivo. Znanstvenici su uspjeli iskoristiti imunosni sustav u borbi protiv raka. Na primjer, postojali su slučajevi gdje smo našli prekidače za gašenje raka, a novi lijekovi mogli su ponovno aktivirati imunosni sustav, kako bi se borio protiv raka. Kao dodatak, postoje metode kojima možete uzeti imunosne stanice iz tijela, trenirati ih, podesiti i vratiti u tijelo kako bi se borile protiv raka. Gotovo zvuči kao znanstvena fantastika, zar ne?
While I was a researcher at the National Cancer Institute, I had the privilege of working with some of the pioneers of this field and watched the development firsthand. It's been pretty amazing. Today, over 600 clinical trials are open, actively recruiting patients to explore all aspects in immunotherapy.
Dok sam istraživao pri Nacionalnom Institutu za rak, imao sam čast raditi s nekima od pionira na ovom polju i gledao sam razvoj iz prve ruke. Bilo je zadivljujuće. Danas je otvoreno preko 600 kliničkih testiranja i aktivno traže pacijente za istraživanje svih vidova imunoterapije.
While these three exciting revolutions are ongoing, unfortunately, this is only the beginning, and there are still many, many challenges. Let me illustrate with a patient. Here is a patient with a skin cancer called melanoma. It's horrible; the cancer has gone everywhere. However, scientists were able to map the mutations of this cancer and give a specific treatment that targets one of the mutations. And the result is almost miraculous. Tumors almost seem to melt away. Unfortunately, this is not the end of the story. A few months later, this picture is taken. The tumor has come back. The question is: Why? The answer is tumor heterogeneity. Let me explain.
Dok se ove tri uzbudljive revolucije događaju, nažalost, ovo je tek početak, i još postoji puno, puno izazova. Predočit ću vam ovo s pacijentom. Ovaj pacijent ima rak kože, melanom. Užasno je, rak se proširio posvuda. No ipak, znanstvenici su mapirali mutacije ovog raka i dali specifično liječenje koje cilja jednu od mutacija. I rezultat je gotovo čudotvoran. Tumori su gotovo nestali. Nažalost, ovo nije kraj priče. Nekoliko mjeseci kasnije, ponovo je slikano. Tumor se vratio. Pitanje je: Zašto? Odgovor je u tumorskoj heterogenezi. Dozvolite da objasnim.
Even a cancer as small as one centimeter in diameter harbors over a hundred million different cells. While genetically similar, there are small differences in these different cancers that make them differently prone to different drugs. So even if you have a drug that's highly effective, that kills almost all the cells, there is a chance that there's a small population that's resistant to the drug. This ultimately is the population that comes back, and takes over the patient.
Čak i rak promjera jednog centimetra sadrži stotine milijuna različitih stanica. Iako su genetski slične, postoje male razlike u tim stanicama koje ih čine različito podložnima na različite lijekove. Čak i ako imate lijek koji je izrazito učinkovit i koji uništi gotovo sve stanice, moguće je da postoji mala populacija koja je otporna na lijek. To je na kraju populacija koja se vrati i preuzme pacijenta.
So then the question is: What do we do with this information? Well, the key, then, is to apply all these exciting advancements in cancer therapy earlier, as soon as we can, before these resistance clones emerge. The key to cancer and curing cancer is early detection. And we intuitively know this. Finding cancer early results in better outcomes, and the numbers show this as well. For example, in ovarian cancer, if you detect cancer in stage four, only 17 percent of the women survive at five years. However, if you are able to detect this cancer as early as stage one, over 92 percent of women will survive. But the sad fact is, only 15 percent of women are detected at stage one, whereas the vast majority, 70 percent, are detected in stages three and four.
Onda je pitanje sljedeće: Što radimo s ovim informacijama? Pa, tada je ključno primjeniti sve ove uzbudljive napretke u terapiji raka ranije, što je prije moguće, prije nego se ovi otporni klonovi pojave. Ključ raka i liječenja raka je u ranom otkrivanju. I intuitivno znamo ovo. Kada rak pronađemo ranije, dobijemo bolje rezultate i brojke to također pokazuju. Na primjer, rak jajnika, ako ga otkrijete u četvrtom stadiju, samo 17 posto žena preživi pet godina. Ako ga otkrijete u prvom stadiju, oko 92 posto žena će preživjeti. Ali tužna činjenica je da samo 15 posto žena dijagnosticiramo u prvom stadiju, a većini, oko 70 posto, bude dijagnosticirano u trećem i četvrtom.
We desperately need better detection mechanisms for cancers. The current best ways to screen cancer fall into one of three categories. First is medical procedures, which is like colonoscopy for colon cancer. Second is protein biomarkers, like PSA for prostate cancer. Or third, imaging techniques, such as mammography for breast cancer. Medical procedures are the gold standard; however, they are highly invasive and require a large infrastructure to implement. Protein markers, while effective in some populations, are not very specific in some circumstances, resulting in high numbers of false positives, which then results in unnecessary work-ups and unnecessary procedures. Imaging methods, while useful in some populations, expose patients to harmful radiation. In addition, it is not applicable to all patients. For example, mammography has problems in women with dense breasts.
Očajnički trebamo bolji mehanizam za otkrivanje raka. Najbolji načini za pronalazak raka spadaju u jednu od ove tri kategorije. Prvo su medicinski postupci, kao kolonoskopija za rak debelog crijeva. Drugo su proteinski biomarkeri, kao za rak prostate. Ili treće, tehnike snimanja, kao mamografija za rak dojke. Medicinski postupci su zlatni standard; no, oni su jako invazivni i traže veliku infrastrukturu za primjenu. Proteinski markeri, iako učinkoviti kod nekih populacija, nisu dovoljno specifični u određenim okolnostima, rezultirajući s mnogo lažnih pozitivnih rezultata, koji potom rezultiraju nepotrebnim pretragama i liječenjima. Metode snimanja, iako korisne kod nekih populacija, izlažu pacijente štetnom zračenju. I dodatno, nisu primjenjive na sve pacijente. Na primjer, mamografija ima problema kod žena koje imaju gusto tkivo dojki.
So what we need is a method that is noninvasive, that is light in infrastructure, that is highly specific, that also does not have false positives, does not use any radiation and is applicable to large populations. Even more importantly, we need a method to be able to detect cancers before they're 100 million cells in size. Does such a technology exist? Well, I wouldn't be up here giving a talk if it didn't.
Tako da trebamo metodu koja nije invazivna, koja nema veliku infrastrukturu, koja je vrlo specifična, da nema lažne pozitivne rezultate, ne koristi zračenje i primjenjiva je na širokoj populaciji. Još važnije, trebamo metodu koja može uočiti rak prije nego zahvati sto milijuna stanica. Postoji li takva tehnologija? Pa, ne bih bio ovdje i pričao, da ne postoji.
I'm excited to tell you about this latest technology we've developed. Central to our technology is a simple blood test. The blood circulatory system, while seemingly mundane, is essential for you to survive, providing oxygen and nutrients to your cells, and removing waste and carbon dioxide. Here's a key biological insight: Cancer cells grow and die faster than normal cells, and when they die, DNA is shed into the blood system. Since we know the signatures of these cancer cells from all the different cancer genome sequencing projects, we can look for those signals in the blood to be able to detect these cancers early. So instead of waiting for cancers to be large enough to cause symptoms, or for them to be dense enough to show up on imaging, or for them to be prominent enough for you to be able to visualize on medical procedures, we can start looking for cancers while they are relatively pretty small, by looking for these small amounts of DNA in the blood.
Uzbuđen sam s vama podijeliti informacije o najnovijoj tehnologiji. Osnova naše tehnologije je jednostavan test krvi. Sustav protoka krvi, iako se čini vrlo običan, osnova je našeg preživljavanja, dajući kisik i hranjive tvari stanicama i uklanjajući otpad i ugljični dioksid. Ovo je ključna biološka stvar: Stanice raka rastu i umiru brže od normalnih stanica i kada umru, DNK se odbacuje u krvotok. Pošto znamo potpise ovih stanica raka, iz svih različitih projekata sekvenciranja genoma raka, možemo tražiti ove signale u krvi kako bismo rano otkrili rak. Umjesto čekanja da rak bude dovoljno uznapredovao i izazove simptome, ili da bude dovoljno gust kako bi se vidio na slikama, ili da bude dovoljno uznapredovao te ga možete vizualizirati medicinskim procedurama, možemo početi tražiti rak dok je još relativno malen, tražeći ove male količine DNK u krvi.
So let me tell you how we do this. First, like I said, we start off with a simple blood test -- no radiation, no complicated equipment -- a simple blood test. Then the blood is shipped to us, and what we do is extract the DNA out of it. While your body is mostly healthy cells, most of the DNA that's detected will be from healthy cells. However, there will be a small amount, less than one percent, that comes from the cancer cells. Then we use molecular biology methods to be able to enrich this DNA for areas of the genome which are known to be associated with cancer, based on the information from the cancer genomics projects. We're able to then put this DNA into DNA-sequencing machines and are able to digitize the DNA into A's, C's, T's and G's and have this final readout. Ultimately, we have information of billions of letters that output from this run. We then apply statistical and computational methods to be able to find the small signal that's present, indicative of the small amount of cancer DNA in the blood.
Dozvolite da vam kažem kako to činimo. Prvo, kako sam rekao, počinjemo testiranjem krvi, bez zračenja, bez složene opreme, jednostavan test krvi. Onda nam dopreme krv i iz nje izvlačimo DNK. Dok su u vašem tijelu većinom zdrave stanice, većina DNK će biti iz zdravih stanica. Ali, postojat će mala količina, manje od 1 posto, koja dolazi iz stanica raka. Zatim, kako bismo obogatili DNK, koristimo metode molekularne biologije, za područja genoma za koja se zna da su povezani s rakom, prema informacijama iz projekata koji su se bavili genomikom raka. Možemo onda uzeti tu DNK i staviti je u sekvencer te možemo digitalizirati DNK u A, C, T i G i dobiti iščitanje. Na kraju, imamo informacije o milijardama slova koja proizlaze iz ovoga. Potom primjenjujemo statističke i računalne metode kako bismo pronašli mali signal koji je prisutan, indicirajući malu količinu DNK raka u krvi.
So does this actually work in patients? Well, because there's no way of really predicting right now which patients will get cancer, we use the next best population: cancers in remission; specifically, lung cancer. The sad fact is, even with the best drugs that we have today, most lung cancers come back. The key, then, is to see whether we're able to detect these recurrences of cancers earlier than with standard methods.
Radi li ovo zaista na pacijentima? Pa, budući još ne postoji način da zaista predvidimo koji pacijenti će dobiti rak, koristimo sljedeću najbolju populaciju: rak u remisiji; konkretno, rak pluća. Tužna činjenica je, i uz najbolje lijekove danas, većina raka pluća se vrati. Ključ je, onda, vidjeti možemo li detektirati povratak raka ranije nego standardnim metodama.
We just finished a major trial with Professor Charles Swanton at University College London, examining this. Let me walk you through an example of one patient. Here's an example of one patient who undergoes surgery at time point zero, and then undergoes chemotherapy. Then the patient is under remission. He is monitored using clinical exams and imaging methods. Around day 450, unfortunately, the cancer comes back. The question is: Are we able to catch this earlier? During this whole time, we've been collecting blood serially to be able to measure the amount of ctDNA in the blood. So at the initial time point, as expected, there's a high level of cancer DNA in the blood. However, this goes away to zero in subsequent time points and remains negligible after subsequent points. However, around day 340, we see the rise of cancer DNA in the blood, and eventually, it goes up higher for days 400 and 450.
Upravo smo završili veliko testiranje s profesorom Charlesom Swantonom sa Sveučilišta u Londonu, proučavajući ovo. Proći ćemo zajedno primjer jednog pacijenta. Ovo je primjer pacijenta koji odlazi na operaciju u nultoj vremenskoj točci, potom ide na kemoterapiju. Zatim je pacijent u remisiji. Prati ga se koristeći klinička testiranja i metode vizualizacije, odnosno slikanja. Nažalost, oko 450. dana, rak se vraća. Pitanje je: Jesmo li ga mogli uočiti ranije? Cijelo ovo vrijeme serijski smo skupljali krv, kako bismo mjerili količinu ctDNK u krvi. Na početnoj vremenskoj točci, kako smo i očekivali, postoji visoka razina DNK raka u krvi. No, to nestaje u kasnijim vremenskim točkama i ostaje zanemarivo u budućnosti. No, 340. dana uočavamo skok DNK raka u krvi i s vremenom, penje se oko 400. i 450. dana.
Here's the key, if you've missed it: At day 340, we see the rise in the cancer DNA in the blood. That means we are catching this cancer over a hundred days earlier than traditional methods. This is a hundred days earlier where we can give therapies, a hundred days earlier where we can do surgical interventions, or even a hundred days less for the cancer to grow or a hundred days less for resistance to occur. For some patients, this hundred days means the matter of life and death. We're really excited about this information.
Ovdje je ključ, ako ste ga propustili. 340. dana vidimo podizanje DNK raka u krvi. To znači da smo primjetili rak stotinu dana ranije od tradicionalnih metoda. Ovo je stotinu dana više u kojima možemo liječiti, stotinu dana više gdje možemo obaviti operaciju, ili čak sto dana manje da rak raste, ili stotinu dana manje da se stvori otpornost. Za neke pacijente, stotinu dana znači razliku između života i smrti. Zaista smo uzbuđeni zbog ovih informacija.
Because of this assignment, we've done additional studies now in other cancers, including breast cancer, lung cancer and ovarian cancer, and I can't wait to see how much earlier we can find these cancers.
Zbog ovog zadatka, odradili smo dodatne studije kod drugih tipova raka, uključujući rak dojke, rak pluća i rak jajnika, i ne mogu dočekati da vidim koliko ranije ćemo uočiti ove vrste raka.
Ultimately, I have a dream, a dream of two vials of blood, and that, in the future, as part of all of our standard physical exams, we'll have two vials of blood drawn. And from these two vials of blood we will be able to compare the DNA from all known signatures of cancer, and hopefully then detect cancers months to even years earlier. Even with the therapies we have currently, this could mean that millions of lives could be saved. And if you add on to that recent advancements in immunotherapy and targeted therapies, the end of cancer is in sight.
U konačnici imam san, sanjam dvije epruvete krvi i da ćemo u budućnosti, kao dio svakog liječničkog pregleda, dati dvije epruvete krvi. I iz te dvije epruvete moći ćemo napraviti usporedbu DNK za sve poznate vrste raka i moći uočiti rak mjesecima, pa čak i godinama ranije. Čak i pomoću terapija koje imamo trenutno, to znači da bi se milijuni života mogli spasiti. I ako tome dodate nedavne napretke u imunoterapiji i ciljane terapije, kraj raka se bliži.
The next time you hear the word "cancer," I want you to add to the emotions: hope. Hold on. Cancer researchers all around the world are working feverishly to beat this disease, and tremendous progress is being made.
Sljedećeg puta kada čujete riječ "rak", želim da dodate emociju: nada. Izdržite. Istraživači raka diljem svijeta vrlo aktivno rade da pobijede ovu bolest i ogromni pomaci su napravljeni.
This is the beginning of the end. We will win the war on cancer. And to me, this is amazing news.
Ovo je početak kraja. Pobijedit ćemo u ratu protiv raka. A za mene, to su odlične vijesti.
Thank you.
Hvala vam.
(Applause)
(Pljesak)