Study Finds Small Cell Lung Cancer Cells Evolve, Highlighting Why Recurrence Occurs

While small cell lung cancer is often resistant to chemotherapy, researchers at The University of Texas MD Anderson Cancer Center in Houston, Texas, found that these tumors evolve with many new and different types of cells appear.

“Our main finding was that small cell lung cancer that was more resistant to chemotherapy were much more complex,” Dr. Lauren Averett Byers, associate professor of thoracic/head and neck medical oncology at MD Anderson, said in an interview with CURE. “If you looked at the individual cells that were making up these tumors, we saw that there were different populations of cancer cells within the same tumor, and one group of cells might have one type of resistance and another group of cells might have another type of resistance.”

While chemotherapy remains the standard of care for these patients, relapse still occurs within weeks to months of treatment. In this study, published in Nature Cancer, the researchers observed that new and different types of cells can occur within small cell lung cancer tumors — something they termed “intratumoral heterogeneity.”

In this interview, Byers discussed their study findings and what this means for patients with small cell lung cancer.

CURE^®: Why is there a particular concern when it comes to chemotherapy resistance in small cell lung cancer?

Byers: One of the major challenges that we face in treating small cell lung cancer is that most patients initially respond very well to chemotherapy…which is essentially all cisplatin- or carboplatin-based treatment, and we get these really good responses initially, but then often, in a very short period of time, the cancer becomes resistant to the treatment and it starts to grow again. In many patients, when that happens, we try other types of treatments like other types of chemotherapy or approved immunotherapies, but most patients don't respond to therapy.

So, this is sort of a unique feature of small cell lung cancer and there's been a lot of questions in the field about why this resistance develops and what's driving it. So that was why we were really particularly interested in trying to learn more about why this was happening in small cell lung cancer, especially after cancer had been exposed to chemotherapy.

You mentioned there’s challenges, what are some examples?

Small cell lung cancer is often very aggressive and grows quickly when it recurs, and it's sort of expected that, in the majority of patients, it will recur. If a scan shows there's been some progression of the cancer, then generally speaking, it's less common for patients to undergo a biopsy to confirm it. And if patients do have a biopsy, the biopsies tend to be very small samples. So, we've had this real challenging situation where we (don’t have enough biopsy samples of small cell lung cancer that has relapsed) after previous chemotherapy in order to try to study why this was happening or what was contributing to it.

What were your main findings?

Because the tumor was very diverse, we think that is a major reason that if you've been receiving one type of treatment or even two types of treatments together, that it didn't seem to be able to hit all of the different cancer cells that had emerged after the prior chemotherapy. That's the most important (part because) we knew that this is a challenging type of cancer to treat because the resistance develops quickly.

Now, we understand better what this looks like and that we need to be able to do two things. One is that we need to bring our most effective new treatments that are being developed as early as possible into the treatment with the goal of trying to prevent the cancer from evolving and adapting. The other thing is that we are also looking at the future. One of the things we want to do is look at whether there are ways to prevent the cancer from being able to evolve and adapt and what's letting (the small cell lung cancer to) become resistant to treatment. And so, there may be ways to prevent it from turning on new signals that help it to escape treatment.

Are there any next steps or future studies being conducted?

There are plans to bring some of the (novel) treatments that look promising for small cell lung cancer — for example, new targeted therapies – to clinical trials to evaluate immediately in a patient after they have finished their initial chemotherapy rather than waiting until the cancer starts to come back. That is very promising.

And then the other thing is, in addition to targeting the cancer cells, we're also trying to understand if there are changes that happen also in the immune cells. We we want to understand if there ways to improve upon the current available therapies or if there are ways to enhance their effect. Again, it is the idea of trying to get our most effective treatments to patients with small cell lung cancer as early as possible.

Is there anything we haven’t touched upon that our audience should know more about?

One of the exciting things from the study is that it shows us why treating small cell lung cancer has been a real challenge and one of the reasons that some of these treatment approaches have not been effective enough.