For this episode of Karger’s The Waiting Room Podcast, we spoke again with Dr Anne-Marie Baird, who currently serves as the president of Lung Cancer Europe (LuCE). She is a Senior Research Fellow at Trinity College Dublin, Ireland, and a patient advocate. In this episode we are going to focus on non-small cell lung cancer, genetic predisposition, biomarkers and treatment.

LuCE is the voice of Europeans impacted by lung cancer. The aim of LuCE is to destigmatise the disease and ensure that those impacted by lung cancer get the care they need to achieve the best possible outcomes.

More information on lung cancer is freely available here:

• Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation
• Infographic Summary Sheets for Patients:

1. KRAS G12C in Metastatic Non-Small Cell Lung Cancer
2. When Checkpoint Inhibitor Therapy Stops Working
3. Biomarkers in Metastatic Non-Small Cell Lung Cancer

Note: The statements and opinions contained in this podcast are solely those of the speaker.

Podcast Interview

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Transcript

Hello and welcome to The Waiting Room, Anne-Marie.

Hi, Susanne. Really great to be back again.

It’s great to have you here again. Last time we met, you explained what lung cancer is and what different kinds there are. We spoke about the signs and symptoms, as well as risk factors and causes for lung cancer. We learned that there are two main subtypes: small cell lung cancer, which accounts for about 15% of cases, and non-small cell lung cancer, which accounts for about 85% of lung cancer cases. So, today, let’s concentrate on the type of lung cancer which is more frequent. My first question to you is what is non-small cell lung cancer and why is it important to differentiate small cell lung cancer and non-small cell lung cancer?

So that’s a great question to kick us off, Susanne, because there are many different types of lung cancer. And as you’ve rightly said, small cell lung cancer is responsible for the least amount of cases. And small cell lung cancer develops in small round cells in the lung called neuroendocrine cells. And they usually tend to grow very quickly and spread early on in the development, and they usually begin in the large airways of the lungs.

When we look at non-small cell lung cancer, there are a number of different types within non-small cell lung cancer. And three of the main types are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. And again, the type really depends on what type of cells that they come from, because obviously in the lungs there are many different cell types, and these all have different types of functions.

So, adenocarcinoma is one of the most common types of non-small cell, and it starts in the mucus-making glands in the linings of your lungs. Then squamous cell lung cancer: This tends to develop in the flat cells that cover the surface of your airways, and it tends to grow near the center of the lung. And then large cell carcinoma: These are a bit like what they say on the tin. They are large abnormal looking cells, and these cells can be found throughout the lung. So then a large cell carcinoma can be found throughout the lung.

So, the reason why we’ve gone into so much detail there, it’s just important to understand there are many different types of lung cancer. It can really depend on what cell they originate from. And it’s really important to know your specific type of lung cancer, because this is the best way to help determine what the best treatment option is for your specific type of disease.

Okay. So, before we come to treatment, I have another question that leads us even deeper into the topic. Can you tell us what makes cancer cells or cells abnormal or different and turns them into cancer cells? Can you ask like this?

Yes, again, that’s another great question. So, I mean, I think if you think of it in its most simplest form, cancer cells are cells that are in the body that no longer obey any rules. So, it’s kind of like you think of rules and regulations. Normal cells obey all of those things. Whereas cancer cells have worked out ways that they can bypass every rule, every regulation that you can kind of have there in the body for your sort of checks and balances, for the body to remain healthy and well.

And these rules, if we think of them like that, tend to be governed by different signals. So, cells will receive different signals and that will help them understand how they are supposed to behave. But of course, cancer cells are doing their own thing and they sometimes don’t even need to receive these signals to do whatever type of behavior they want to do. So just to give a couple of examples, if that’s okay, Susanne. So, for example, cells can receive signals to grow. And normal cells will only grow when they receive this specific signal to do so. But a cancer cell can grow and do whatever it wants in the absence of these signals. Cancer cells can also ignore signals that it gets, telling them to stop dividing, or that, you know, now is the time for those cells to die. Again, normal cells can’t ignore those signals.

And then if we look, for example, in the immune system, the immune system usually gets rid of cells that are damaged or abnormal. The cancer cells, again, have worked out ways to hide from our immune system, so the immune system doesn’t recognize them as damaged or abnormal, and they continue to do their own thing within the body. And these changes in the behavior, these changes in how they look and obey or disobey the rules is really down to changes or mutations in the DNA of our cells. And usually a cancer cell will have accumulated a number of different mutations. And then this influences that bad behavior that I’ve sort of talked about there.

So, mutation is a very, very important keyword, and I guess that this is important for treatment as well. So, you target these mutated genes to treat cancer?

Not quite. So, it really just depends. So obviously, as I’ve said, cancer in and of itself is very complex and there’s many, many different types. Sometimes within a cancer there might not be a specific mutation that’s identifiable for whatever reason. And in other cancers, there might be a mutation identified, but there’s not necessarily a treatment available to target that specific mutation, if that makes sense.

But of course, we do know that cancer cells tend to divide very rapidly because again, they’re not obeying any of those rules or regulations, they’re doing their own thing, and they tend to divide very rapidly then. So that’s why you know chemotherapies would have been used, because chemotherapies target those very rapidly dividing cells. And then in that way, chemotherapy can kill cancer cells.

But if you think about where we find specific mutations in a cancer cell, given the advances that we’ve seen, we now have treatments that can target those specific mutations. So, they’re targeting the kind of the defect or the rule that’s being disobeyed within a cancer cell. And this is referred to as targeted therapy. So, in lung cancer, this could be something like ALK ROS1, EGFR or more recently we’ve seen it in KRAS G12C. So, it really just depends on the type of cancer that you have and what mutation may have been identified within it.

So you still have chemotherapy to treat lung cancer and targeted therapies as well. If you use targeted therapies, how do you know what mutation causes this special kind of cancer? How do you know which mutation to treat?

So again, another great question. I guess to give it a very broad term and this goes by a number of different terms, but there’s something called biomarker testing or molecular tumor testing. But depending on where you are, there’s various iterations of that wording. But this is to look at different possible markers in a tumor. So, this could be looking at the genes, those mutations we talked about. It could be looking at different proteins, maybe on the surface of the cancer cell. And by looking at these biomarkers it can provide a lot of different information about an individual’s particular cancer type.

And then these biomarker tests can help to identify what type of treatment might be best for someone’s specific tumor. So, it is important to note, though, that sometimes someone can have a biomarker test done, but it may not be necessarily where they will find something. So, you can have a biomarker test, but they might not find a specific mutation or protein. But it’s always very important to talk to your doctor as to whether or not your tumor should undergo biomarker testing.

So, biomarker testing is an important part on the path to treatment. Can you tell us how a test for biomarkers is done?

So, biomarker testing can be done in different ways. Usually, it’s done with a sample of the tumor. This is where you would often hear the term “a biopsy was taken”. A biopsy would be taken to determine or not whether a cancer is present. Is it normal tissue? Is it a cancer tissue? If it’s a cancer tissue, what type is it? So, you know, we talked about adenocarcinomas, squamous cell carcinoma, all of that at the beginning of this. So, the tissue is a way in which to do that.

But you can also look much deeper as well with the biomarker testing, looking at those genes, looking at those proteins. And all of this can be done in the lab, and pathologists will look at all of those different results then to help determine what particular type of – well, in the instance I’m talking about lung cancer that might be there – and they can do this, as I said, by looking at the proteins, by looking at the genes. Sometimes they look at one gene at a time, sometimes they look at multiple genes all at one time, which is sometimes referred to as panel testing.

It really just depends what would be available within the center that you’re being treated at or where you’re having your tests, you know, it can vary a bit unfortunately. Now in more recent times, people have also been looking at blood samples. Although tissue is kind of the more traditional option. There are other options now where you can take a blood sample and you could do some tests on the blood sample to help determine whether or not someone has a biomarker on their tumor as well.

So, a biomarker is like a passport. You know a lot of about the cancer, the type of cancer then. And you touched on it briefly at the beginning of our interview: treatment. Could you tell us more? What treatment options are there for non-small cell lung cancer?

So, it really again depends. There’s not going to be a one size fits all approach; an individual’s tumor is as individual as they are, really. So, it depends on the specific type of non-small cell lung cancer you have, whether or not your tumor has one of those biomarkers we talked about. It also depends on whether do you have lung cancer that’s an early-stage disease, is it late-stage disease and how are you in and of yourself? Like, you know, how well do you feel, how/what type of treatment option might be best for you depending on your circumstances.

There’s a couple of things involved when we talk about treatment options. But realistically, when we talk about lung cancer and again, it will depend on the specific type of lung cancer you have and your stage. It could be surgery, it could be chemotherapy, it could be radiotherapy, it could be a mix of those. There could be immunotherapy, which is something we haven’t really talked about. So, this is a treatment that helps your immune cells kill a cancer.

And then obviously we talked about those biomarkers. So, there could be treatments where it’s called targeted therapies. So, those drugs that are targeted towards a specific change within your tumor and those are usually referred to as tyrosine kinase inhibitors based on the type of genes where these mutations are found. So, it really just depends on your specific type of disease. And this is why it’s so important to find out your specific type of disease, because it really then can have an impact on what type of treatment might be best for you and your tumor.

You said it before: There is no “one type fits all”. So, it is a very individual thing. Your cancer is individual, and your doctor and you, you find an individual treatment then. Can I ask you as a researcher and a patient advocate, what has been the most promising development in treatment of lung cancer in the last five years in your opinion?

So, my opinion, first off, I think just the advancements and the understanding of the biology and the complexity of lung cancer has been really, really important. Because, you know, prior to this, decades ago, it was kind of all lumped into one big thing: It was a lung cancer. Whereas now we know that there’s many, many different types. So, I think that understanding of the complexity has been so, so important. Now that obviously has been outside of the five years, so I do apologize.

I also believe the newer treatment options that have come in, again in the last decade or so and beyond, whether it’s the targeted therapies, the immunotherapies, all of these different and novel treatments, have really made a big difference in the lung cancer community. So, I hope that as we find out even more about the complexity of the disease, we’ll find out maybe more markers that can be used to personalize treatment options to individual people with this disease.

However, I would say on balance, while there has been great improvements, we also need to understand that we need equity in access as well. So, when there’s an advancement within, and again, I’m only speaking specifically to lung cancer, because that’s my background. But where there is an advancement, whether it’s testing for a marker, whether it’s a novel treatment, whatever it might be, we need to ensure equity in access for all, so that whoever it is that has been diagnosed with the condition has the best possible outcome. So, it shouldn’t depend on where they live or how much money they earn or any of those types of things. So, we have to strive for not only advancements, but equity within those advancements as well.

Thank you. That’s a very important point and I think you can’t stress it enough: equity and access. I think there’s been a lot to take in during this episode. So, we want to encourage our listeners to have a look at the various infographic summary sheets you helped preparing. Thank you very much for all the helpful information you shared with us, Anne-Marie. Again, this was a profound conversation.

Thanks so much for having me, Susanne.