Kevin Harrington, oncologist: ‘Conjugate drugs will forever change our ability to kill cancer cells’ | The science

Oncologist Kevin Harrington (London, 61) has spent decades facing a little-known enemy that leaves scars that are hard to hide. It is head and neck cancer, the seventh most common tumor in Spain, with approximately 12,500 new cases reported each year. It is treatable if diagnosed early, but patients spend the rest of their lives with significant physical and psychological scars.

Harrington, a radiotherapy specialist at the British Cancer Research Institute, is looking for a way to diagnose and treat these tumors as quickly as possible to prevent them from recurring…

Oncologist Kevin Harrington (London, 61) has spent decades facing a little-known enemy that leaves scars that are hard to hide. It is head and neck cancer, the seventh most common tumor in Spain, with approximately 12,500 new cases reported each year. It is treatable if diagnosed early, but patients spend the rest of their lives with significant physical and psychological scars.

Harrington, a radiotherapy specialist at Cancer Research UK, is looking for a way to diagnose and treat these tumors as quickly as possible to prevent them from recurring. Visiting Spain to attend a conference organized by the CRIS Cancer Foundation, which funds his work, the doctor speaks clearly about the future of cancer treatment, which will cost more than a million euros per patient, and the growing difficulties in reaching everyone. citizens.

Ask. You use a combination of all available cancer-fighting tools: surgery, chemotherapy, radiation therapy and immunotherapy. Are they enough to win the battle against cancer?

Reply. Very often we use the analogy of war to explain cancer. I myself talk about fighting cancer and defeating cancer. However, patients do not like this at all because it turns them into a battlefield. Sometimes this makes them think that if they haven’t recovered, it’s because they didn’t do enough.

TO. What do you tell your patients?

R. That from now on we are forming a team. Many people feel guilty about cancer, for example if they smoked and had children or a wife. It is very important to avoid this guilt. In the cancers I treat, 60% of diagnoses are due to the human papillomavirus. Most of the rest comes from tobacco. There are people who smoke all their lives and die of old age. Another smokes for five years and develops cancer. Basically, it’s bad luck. I tell patients that we will try to solve the problem with available treatments. I have seen patients apologize for not responding to treatment. In medical jargon, we even say that a patient’s chemotherapy has failed. It’s horrible. The truth is that the treatment did not help them. It’s our fault, not yours.

TO. And yet, you yourself use the metaphor of war?

R. This is a good analogy for how cancer research works. There are times when we break through the enemy line and make a breakthrough, but then the forces are redistributed and we return to a stalemate.

TO. What moment are we at now?

R. In one of the phases of paralysis and disappointment. We know that immunotherapy will be our best weapon against cancer, perhaps against most tumors, once we understand how to use it correctly. We are seeing enormous progress in the treatment of melanoma: more than half of patients survive their tumor, whereas previously the majority died within a year of diagnosis. But for head and neck cancer, the response rate is 15%. The situation is similar in other tumors. We use trial and error to find treatments that will improve these indicators. Fortunately, we can now do biopsies and blood tests, know what’s going on with the patient’s immune system, and even change treatment based on that.

TO. Head and neck cancer is not one of the tumors that people usually talk about. What challenges does it present?

R. I am a specialist in radiation oncology, and this is one of the most difficult tumors to treat with this method. This is due to the delicate anatomy of this area, as tumors differ greatly from each other. A tumor on the tongue is very different from a tumor in the larynx, although at the cellular level they are the same. The reason for the difficulty is that the operation often leaves very visible wounds. This can affect the voice, and in other cases part of the jaw may have to be cut out and replaced with bone from the arm. There are patients who stop salivating, others lose their sense of smell or taste, cannot swallow, or are left with so many scars that their young children are afraid. I have patients who avoid going outside to avoid unpleasant looks.

TO. What are your chances of survival?

R. With early diagnosis, the cure rate is 90%. But in half of the cases it is detected in advanced stages, and only 40% of patients are cured; which means that most of them will die within five years. In recent years, indicators have improved slightly, but not enough.

TO. What new treatment are you researching?

R. Immunotherapy. We already demonstrated in 2016 that it is better than chemotherapy in patients with recurrent head and neck tumors. We conducted the first trial on patients who had no choice. And for some it worked. This tells us that we could use it early on, right after diagnosis, and treat them without the tumor coming back. Now the practice has changed and it is now the first line treatment.

TO. What’s the next step?

R. May this work on more patients. Currently, in almost 80% of cases this does not work. What combination do we need to increase response rate? Immunotherapy can act like a vaccine, preventing the tumor from returning. In recent years, we have conducted several trials in which we were unable to use immunotherapy along with radiation and chemotherapy. We have now begun to design and conduct new clinical trials again.

TO. Something similar happens with other types of tumors.

R. Yes, that is why we are going through a period of disappointment. We are beginning to understand why treatments work for some patients and what characteristics make tumors more vulnerable. But despite this, there are cases when the patient has all the signs of a reaction, but it turns out that there is none. It also happens that others are cured despite everything. We really don’t know what pattern to look for. We are trying to figure out which image is a puzzle without having all the pieces. But there is a huge international effort to analyze this problem, and funding from the CRIS Foundation is helping us a lot in this. In addition, the development of artificial intelligence can help us find patterns that we do not see. That’s why I believe we are at the gates of a new revolution in therapy, a new great advance in the fight against cancer.

TO. There are tumors that do not respond to immunotherapy.

TO. Yes, pancreas, some types of colon, glioblastoma of the brain. But I’m optimistic. I believe we will see new generations of immunotherapies that can target the immune system against cancer, which in turn will be used in conjunction with drugs that directly target the cancer. And if the patient’s immune system doesn’t respond, we have CAR-T, which helps us recruit an army of anti-cancer cells in the laboratory and transfer them to the patient.

TO.Can drugs that directly target tumors be improved?

R. Yes, there will be two big achievements. Firstly, these are conjugate drugs. For example, in pancreatic cancer, there are cells that isolate the tumor so that the immune system does not detect it. In these cases, antibodies will appear that are designed to selectively bind to these cells and carry a very powerful immunotherapy drug. These new drug conjugates will forever change our ability to kill cancer cells. Another powerful weapon is antibodies, which carry radioactivity directly to tumors. This would be a type of ultra-targeted radioactivity with a precision equivalent to the diameter of a cell. The big question is how to combine these treatments and make them tolerable for the patient. Another factor is cost. This is not a cheap treatment and will only be available to health systems that can spend large sums of money.

TO. Are you afraid that only the most privileged people will have access to the best cancer treatments?

R. The truth is that we already live in this world. In our countries, the healthcare budget is limited. You can always spend more. In the UK, our healthcare system is running at full capacity. If before the next election a candidate said, “I’m going to raise taxes to get better health care,” a majority of voters would probably oppose it. These new drugs will greatly increase the stress because they really do cost a lot of money.

TO. How much does it cost?

R. More than a million euros per patient. If I spend this money, I will save the patient, but our society will have to decide whether to do it or not.

TO. Does it seem fair to you that the company charges this amount for each patient?

R. I don’t know what to answer because we don’t know how much it costs to develop these treatments. What I do know is that the level of scrutiny and analysis that companies and doctors undergo during clinical trials is enormous and very expensive. When companies claim that their bets are driven by huge R&D costs, there is some truth to it. These companies have shareholders and must generate profits and funds to continue research. Otherwise, the flow of innovation stops. I don’t necessarily like this system or its capitalist orientation, but it is an engine that drives progress in developing new cancer treatments.

TO. Can we ask for more transparency about these costs?

R. In an ideal world, yes. But this will have a negative impact on the share price of these companies, whose main goal is to serve their shareholders.

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