Why Patients With the Same Cancer Respond Differently to Treatment

Ahead of World Cancer Research Day, an oncologist explained why cancers that look alike can respond differently to the same treatment and which areas of research could change how cancer is treated in the next five to 10 years.

Dr. Miguel Gonzales-Velez is a medical and thoracic oncologist at Hackensack University Medical Center and John Theurer Cancer Center. His research focuses on thoracic (chest) cancers, mainly non-small cell lung cancer and small cell lung cancer, as well as phase 1 clinical trials, which test the earliest medications in people before they are approved for general use. He also discussed the gaps in who can reach clinical trials and what patients most often misunderstand about joining one.

CURE: Why can two patients with similar cancers respond differently to the same treatment?

Dr. Miguel Gonzales-Velez: Each cancer is independent, and each cancer behaves in different ways. That's what we call cancer heterogeneity, an important word meaning very many differences. This happens because each cancer develops from different origins.

We're trying to get to what we call personalized or individualized medicine, where we are able to identify each specific cancer and attack them in different ways. However, this is very challenging in practice because cancer has what we call escape mechanisms. These are ways of the cancer becoming smart and changing its ways of growing or hiding from the immune system. That way, it protects itself and continues to grow and create problems.

How do biomarkers help doctors match patients with cancer to treatment?

The basic idea is that the cancer has different proteins. If you have the yellow protein, you get the yellow medication. If you have the red protein, you get the red medication. But this doesn't work all the time. Ideally, we need to find good receptors or good markers of proteins where the medications we have can attack the cancer.

What is the tumor microenvironment, and why does it matter in cancer treatment?

One of the biggest differences when we study cancer in the lab is that the cancer doesn't live isolated. The cancer lives in a little house, depending on the organ, which is called the tumor microenvironment. This neighborhood is composed of normal tissue, like the architecture or the walls of the house. Within this house, there are also parts of the immune system, which are like the plumbing and the electricity system.

Sometimes we don't only attack the cancer itself. We need to activate some sort of inflammation or activate the tumor microenvironment, to activate the neighborhood, so we can eradicate the cancer and kill it so it doesn't grow in other parts of the house or other parts of the neighborhood.

What can researchers understand about a patient's cancer today that was not possible 10 years ago?

Compared to 10 years ago, we understand better that cancer is not one single entity with a one-size-fits-all approach. Different cancers need to be attacked in different ways, with chemotherapies, immune therapies, targeted therapies, protein therapies and hormonal therapies. When we overlap or combine those in different ways, we have better effects. Right now, for most cancers, we have at least three or four different ways of attacking them to get better effects.

What areas of cancer research could change treatment in the next five to 10 years?

The two parts of cancer research that excite me the most are the new treatments that we have. We have new therapies called ADCs, which stands for antibody-drug conjugates. It is a specific type of protein that has another component, like a chemotherapy or like an immunotherapy. So it's a better, more precise way to deliver medications.

The other area is what we call cellular therapies. These are ways to activate the patient's own immune system to protect them from the cancer. There are different ways of activating the immune system. We can do it through vaccines, through proteins that boost the immune system and by boosting what I mentioned earlier, the tumor microenvironment, to protect the person from the cancer.

Why has small cell lung cancer research received less attention?

I think the one area that hasn't received enough attention in the last 30 years is small cell lung cancer. It has been so difficult to make advances in small cell lung cancer that there has been a multiyear gap of very little research. But now, finally, in the last few years and in the coming years, we will be making some advances in new therapies for small cell lung cancer, which is the most aggressive lung cancer that we have right now.

What barriers keep patients from accessing cancer clinical trials?

At a national level, we have a deployment problem in clinical trials. Unfortunately, clinical trials are focused mostly in bigger cancer centers, and they are usually in the biggest cities. There are some areas in the U.S. that we call clinical trial deserts. These are places where you live very far away from a clinical trial and very far away from a large institution.

This is a problem because we can have the best clinical trials, but if patients don't have access, there is going to be a bottleneck. We're going to have a lot of clinical trials in the cancer centers but not enough patients, and a lot of patients living far away from cancer centers. We need to improve the delivery of clinical trials in what we call smaller local community practices. We need to work collectively as a country and as cancer institutions to be able to deliver this care to patients in the community.

What do patients most often misunderstand about cancer clinical trials?

The most common misunderstanding I see is that patients think they are going to be treated as guinea pigs or that they are not going to get the best treatments available. Clinical trials are most of the time designed in ways that try to be fair to patients and give them the benefit of having a good treatment.

There are some cancer trials that use what we call placebos. These are fake medications, or sugar pills. When placebos are used, it's most of the time done in ways that help us understand if the medications really work, and patients get potential access to the real medications after the clinical trial.

How are placebos used in phase 3 cancer clinical trials?

Placebos are usually used in the most advanced trials, what we call phase 3 trials. They are usually used when we're trying to compare the new medication with what we call the standard of care [the treatment typically given for that cancer]. We need to do a real head-to-head comparison so we're able to compare apples to apples and understand the real benefits and the real toxicity, or side effects, of the medications.

How do cancer clinical trials protect patient safety?

It is very important to understand that clinical trials are designed with the patient's safety in mind. Before we go into a clinical trial, we try to ensure that the patient is getting the best care and that we're able to do it as safely as we can.

When patients go into a clinical trial, they get a full assessment to make sure their body and organs are working OK, including the kidneys, the liver, the lungs, the heart, the markers of inflammation and the markers of infection. We make sure that we do not make anything worse for the patient.

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