– Det kommer store gjennombrudd i persontilpasset kreftbehandling

Professor Ronald DePinho leder en forskningsgruppe som har gjort en rekke store oppdagelser som hjelper oss med å utvikle bedre metoder for å oppdage kreft tidlig.

De studerer molekylære og biologiske prosesser som styrer utviklingen av kreft, slik at de kan forbedre kreftpasientbehandling og utvikling av nye medisiner. De studerer molekylære og biologiske prosesser som styrer utviklingen av kreft, slik at de kan forbedre kreftpasientbehandling og utvikling av nye medisiner.

Torsdag holdt han åpningsforedrag på Onkologisk forum på Holmenkollen i Oslo. Her møtes 400 kreftleger i to dager for å dele kunnskap om fronten i kreftbehandlingen.

Kan analysere kreftgenene

– Vi er i en spennende tid i krefthistorien, fordi vi nå har sekvensert mange av genene som er unormale i forskjellige kreftformer. Noe av det første vi lærer er at en aspirerende kreftcelle må tilegne seg spesifikke genetiske mutasjoner for å bli en kreft i utgangspunktet. Vi har nå medisiner, målrettede terapier eller smarte bomber om du vil, som kan målrettes direkte mot de spesifikke genetiske endringene, sier DePinho.

Han forklarer at det gir onkologene en mulighet til å se på genene som er unormale i den enkeltes kreft. Da kan de gi persontilpasset kreftbehandling – det vil si det riktige legemidlet til riktig pasient til rett tid.

– Det har vært en revolusjon av såkalt målrettet terapi. Men det er veldig viktig for pasienter som får diagnosen kreft å få svulstene genetisk profilert, sier han.

Forebygge kreft

– I foredraget ditt kom du også inn på hvordan vi kan forebygge kreft?

– Faktisk vil én av to menn og én av tre kvinner utvikle kreft i løpet av livet. Det som er bemerkelsesverdig er at opptil 50 prosent av krefttilfellene kan forebygges med kunnskap vi har i dag. Disse kreftskaperne inkluderer alkohol, tobakk, virus som HPV, tidlig UVA-eksponering og så videre. Faktisk er mange av disse årsakene operative i barndommen, for de fleste voksne røykere begynner som barn, sier han.

Han forteller at fedme hos barn fremmer utviklingen av visse kreftformer senere i livet. Derfor er det viktig at vi som samfunn er opptatt av å beskytte helsen deres.

– Vi må hindre dem i å bruke tobakksprodukter og sørge for at de trener og har et godt kosthold som forhindrer fedme. Vi må også passe på å beskytte dem mot solen. Tidlig UV-eksponering i barndommen, i form av solbrenthet, kan forårsake hudkreften melanomtype senere i livet. Selvfølgelig er det vaksiner som kan forhindre HPV-kreft, men de må helst gis ved 11 årsalderen, sier DePinho.

Han tror at alt dette til sammen kan ha en større innvirkning på kreftproblemet over hele verden enn den konstante utviklingen av medisiner.

– Vii vet jo at legemidlene ikke nødvendigvis behandler uten å gjøre skade. Det aller beste man kan gjøre er å leve en sunn livsstil og forhindre å få kreft i utgangspunktet, avslutter professor forskeren.

--

Nedenfor følger en transcript av intervjuet.

DePinho: We're at an exciting time in the history of cancer because we've now sequenced many of the genes that are abnormal in different cancers. And one of the first things that we're learning is that an aspiring cancer cell needs to acquire specific genetic mutations in order to become a cancer in the first place. And we now have drugs, targeted therapies, smart bombs that can be squarely directed at those specific genetic alterations.

So it gives oncologists an opportunity to look at the genes that are abnormal in that individual's cancer and provide personalized cancer therapy, the right drug for the right patient at the right time. So that's been a revolution of so-called targeted therapy. So it's very important for patients who are diagnosed with cancer to get their tumors genetically profiled. In addition, a recent Nobel Prize was given for understanding not just the cancer cell, but how the immune system works in cancer.

And what we've discovered is that cancer is able to suppress the immune system. That it puts a break on the immune system. And a whole new class of drugs have now been developed that can unleash the power of the immune system. They're drugs that target the brake and they deactivate the brake and then the immune system is able to recognize the cancer and defeat the cancer.

And indeed, many patients with advanced disease are now using immune therapy to try to elicit more durable responses and even cures in those patients. And so I'd say the combination of targeted therapy and immune therapy is very important and very important for the cancer patient and their doctor to profile the cancer so they know which targeted therapy and which immune therapy to give either alone or in combination for that cancer.

So it's really a remarkable revolution in the last ten years that has given patients and their family new hope based on science.

HT: You mentioned in your lecture the KRAS oncogene driver. What kind of drugs can you use to inhibit this type of cancer?

DePinho: Yes. So that's a great example of how decades of science have, first of all, identified KRAS as the most common oncogene driver. And now we have therapies that can deactivate the mutant KRAS. And that is a very common mutation in lung cancer and pancreas cancer and colon cancer among the most lethal and among the most common cancers in patients.

And we're seeing very excellent activity in those cancers for which there was no hope. And so seeing these responses gives us the ability to not only use those drugs in those patients, but to also then build on those responses and maybe combine cross inhibitors along with immune therapy, for example. And so you're going to start to see not just crass, but crass in combination with other drugs, as well as a very exciting example.

HT: You have a handful of these very effective, targeted therapies. Do you think science will be able to give us more of these drugs in the future?

DePinho: Yes, well, I think that first of all, just in the example of the immune therapy drugs, most of the drugs that we have deactivate the brake on a particular immune cell called a T cell. Those are the soldiers of the immune system and they are the killer cells. However, there are other cells as well, and we're learning that in those patients that don't respond to T cell therapy, that these other cells are suppressing the T cells.

And so now a whole new class of drugs are being directed at these other cells called myeloid cells. And I think over the next ten years, you're going to see more and more of these myeloid therapies come into the clinic and be used in combination with the T cells.

There's also cellular therapy where T cells that have been engineered to become professional killers, and those engineered cells are able to recognize specific proteins on cancer cells and target those cells specifically so called CAT-T or you're going to see CARs and natural killer cells. That's going to be also a very important aspect of immunotherapy, that very exciting aspect.

HT: So immunotherapy, CAR-T therapy and also targeted therapy, that's where the cancer treatment is going the next years?

DePinho: And it's also understanding what therapy to use in which patient at the right time, to apply the right targeted therapy, the right immunotherapy of the right cellular therapy, and the right combinations for that patient based on their specific disease alterations. That is Personalized cancer therapy.

HT: Also, in your lecture, you touched upon how we should avoid getting cancer? Cancer is often discovered in late stages which makes it not curable in most instances, unfortunately.

DePinho: Yes. Well, in fact, one in two men, one in three women will develop cancer in their lifetime. What is remarkable is that up to 50% of cancers can be prevented with knowledge we have in hand today. And these instigators of cancer include alcohol, tobacco, viruses like HPV, early UVA exposure and so on. In fact, many of the instigators of cancer are operative during childhood, so most adult smokers start as children.

Childhood obesity fuels the development of certain cancers later in life. Early UV exposure during childhood skin peeling sunburns can also cause melanoma, a skin cancer later in life. And of course, there are vaccines that can prevent HPV cancers, but those need to be given at age 11 optimally. So I think that we as a society have to protect the future health and well-being of our children and make sure that we're, you know, preventing them from getting using tobacco products in the first place, making sure that they exercise and they have good diet to prevent obesity, protecting them from the sun, you know, and also making sure that they're properly vaccinated.

I think all of those things together could have an even greater impact on the cancer problem worldwide than getting cancer and curing those cancers. Because those are you know, the treatments are not necessarily treatments that are without harm. So the best thing to do is to live a healthy lifestyle and prevent getting cancer in the first place.

But in the meantime, your and your colleagues in your lab in M.D. Anderson is working hard to give us new drugs.

That's correct. And I think this community as well, you know, Norwegian scholars of cancer science have contributed mightily to the development of drugs or the knowledge that has led to drugs and so on. And I think what's really special about this community is not only do you have fantastic basic researchers, but those researchers are working hand in hand with their clinical colleagues to bring the latest knowledge to impact patients and their families.

And so it's really inspiring to see that Viking's spirit of exploration be delivered, to really help patients in need. And the world owes a tremendous debt of gratitude to this community and to Norway for its outstanding science and its commitment to patients.

HT: Professor Ronald DePinho, thank you for talking to us.

DePinho: My pleasure.