«Cancer will never be eradicated, because it is inherent to human beings.» Statements like this one by Mariano Barbacid (Madrid, 1949) will come as a blow for many. But that does not make this eminent biochemist and oncologist stop talking with great frankness when he refers to the disease. And no wonder. According to the World Health Organization, it affects one in three men and one in four women at some point in their lives. «Society has to know the truth. Cancer is very complex and we will never find a cure, but we are going to use every available weapon against it», adds this scientist, head of the experimental oncology group at the Spanish National Cancer Research Centre (CNIO).
Member of the prestigious National Academy of Sciences of the United States, Barbacid focused on the study of cancer after completing his doctorate in biochemistry, which happened, in a way, by chance. To explain this situation, this oncologist likes paraphrasing something mountaineers often say when asked why climbing this or that mountain. «They usually say that just because it was there. And something similar happened to me with this disease.»
In 1982, the USA National Cancer Institute, managed to isolate an oncogene in a human tumour for the first time, a gene that can cause cancer while mutating. In 1998 he returned to Spain after twenty years researching in the United States and came back with the assignment of creating CNIO, which has become one of the top research centres in the world in over a decade. He ran it until 2011, when he decided to devote his time to research only. Professor Barbacid activated a pioneering network of tumour banks and designed an oncochip that enables us to unravel molecular alterations that cause a single cell to become cancerous. A few months ago he was awarded an honorary PhD by the University of Barcelona, another distinction to include on his extensive list of awards and recognitions.
Society perceives that lately we are immersed in a cancer pandemic. More people are dying from the disease. Is it only a perception or is it a reality?
But young people also get cancer.
Thanks to advances in biomedicine in the past thirty years, oncologists claim that two in three cancers are either cured or become chronic.
It increases survival rates, but mortality figures have hardly changed in the last half of a century. How can this paradox be explained?
What factors increase the chances of having cancer?
And if we got rid of these three factors?
Why is it so difficult to treat these mutations?
|«Society needs to understand that cancer is inherent to our existence»
«There are more cancers than infectious diseases. Nobody confuses cholera with AIDS. And yet, people talk about lung cancer in a generic sense»
«I am not trying to give bad news, but nonsmokers, people who do not sunbath and with no chronic damage can also develop cancer»
«Chemotherapy is very effective. But now we are seeing that even drugs that have shown very good results in the treatment of tumours become ineffective after some time»
Despite advances in understanding the disease, chemotherapy, radiotherapy and surgery remain the most standardised treatments.
Yes, good old chemotherapy is very effective. But now we are seeing that even drugs that have shown very good results in the treatment of tumours become ineffective after some time, because people eventually develop a resistance. Tumour cells are evolving entities that change rapidly. Furthermore, the tumour itself is not a single tumour, but many. A cell begins to add up mutations and at a given moment different clones start mutating differently. When we do a biopsy of the tumour in a cancer patient, we extract a piece of the tumour and then we sequence its DNA. We are going to find a mutation in it, but it may well only be present in 30% of that tumour. Cancer is much more complex than we thought. We should, and in fact the possibility already exists thanks to new ultra-sequencing techniques, sequence the human genome of each patient and tumour, because then we would know all the mutations it has. Do you know how many mutations does a lung adenocarcinoma have on average?100? 200? 500?
Around 30,000 in its genome. The four types of cancer that have more mutations are melanoma, lung adenocarcinoma and lung and bladder squamous carcinoma. And all four of them have an external mutational component: tobacco and sun exposure. And it is not a hypothesis, it is already documented. We have a very complex enemy, as if we had a different infection and a hundred viruses at a time. And it is important to make society aware of it. Hiding it would be like the current crisis: we lived happily because we did not know we were in the middle of one. We have to diffuse the enormous complexity of cancer, both scientists and the media.
Ultra- sequencing techniques enable us to know which mutations each tumour has. It is a first step.
Of course, that is basic. Now, it is only part of the equation. The fact that there is a mutation does not tell us how it works, let alone how to inhibit the mutated protein. I will use an analogy. It is as if I told you that there is a terrorist cell in Barcelona that will cause a problem and I give you the ID number of all people living in Barcelona. Among these numbers there are the terrorists’, but how do we identify them? We do not know where they live, or how they look like, when they are going to act … Regarding our work, the Ras signalling pathway has about fifteen or twenty kinases, which are molecules against which it is relatively non-complex to make an inhibitor. A selective inhibitor is more difficult, though. The problem is we do not know which of these kinases are crucial. The complexity of a cell is infinitely superior to sending a man to the moon. Intervening when the function of a cell is altered without affecting healthy cells is a very difficult challenge. I am a researcher, I do not see the cancer patient’s everyday life, but what I am sure of is that if a pancreatic tumour has at least twelve mutated pathways, if we attack it with one or two drugs we will get but a small profit. If we really want to cure the tumour, we have to tackle it from the twelve mutated pathways. But what is the problem, then? Drugs are toxic. If you add a drug that is well tolerated to another drug that is very well tolerated and yet another one, there will come a time when they are no longer tolerated. We will have to make an effort to design more specific drugs, and that is not going to be easy.
Not very good news for those suffering the disease…
In order to do this your experimental oncology group at CNIO have developed a new kind of mouse.
You were elected member of the National Academy of Sciences of the United States, a privilege only a few Spaniards have had access to.
«It may seem there is no room for hope, but the problem is that cancer is very complex and won’t be solved in coming years»
«Both scientists and the mass media have to communicate the great complexity of cancer»
© Mètode 2014 - 83. Online only. The Digits of Science - Autumn 2014