How genes and genetic biomarkers affect lung cancer

Genetic Biomarker Testing for Lung Cancer: What You Should Know

When you find out you have non-small cell lung cancer, it’s important to know if your type of lung cancer has certain genetic markers. It could affect your treatment options.

Some lung cancer gene mutations can help doctors determine a treatment plan. Doctors call these mutations “biomarkers.”

Certain lung cancer biomarkers are important to understand and treat differently, says Heather Wakelee, MD, a thoracic oncologist, professor, and chief of the Division of Medical Oncology at Stanford University Medical Center.

EGFR (epidermal growth factor receptor) is probably the most common. About 10 to 15% of non-small cell lung cancers are EGFR positive, meaning they have a cancerous mutation of the EGFR gene.

It’s what doctors call a “driver mutation,” meaning it’s the reason cancer exists. This mutation is often found in certain people with lung cancer, such as:

• no smokers
• Women
• People of Asian or East Asian descent
• Those who have lung adenocarcinoma (a type of lung cancer)
• Young adults with lung cancer

Genes and lung cancer

When you hear the word “genes,” you might think of the ones you inherit from your parents. But while the genes and lung cancer are linked, very few known genes can transfer an increased chance of lung cancer from parent to child.

There are some exceptions. When several members of a family have lung cancer without an obvious external cause (such as of smoking), you may want to see a genetic counselor, says Kerry Kingham, senior counselor in cancer genetics at Stanford Health Care.

“But even in those [people]we don’t often find the cause,” says Kingham.

Only about 1% of lung cancer cases come from inherited mutations.

“And when we find the inherited mutations and can test other family members, there’s no really good guide that tells us exactly what to do for them other than more careful testing,” says Kingham.

What’s far more important, he says, is analyzing cancer cells after diagnosis.

Small pieces of genetic material (which your doctor may call “proteins”) inside previously healthy lung tissue cells can change or “mutate” to form cancer cells. As cells divide, they continue to pass on these changes, or “mutations,” to new cells, which form tumors.

Doctors don’t know what causes these mutations. But you don’t inherit them from your parents and you can’t pass them on to your children. It’s also not your fault if you get them. These mutations “just happen,” says Kingham. “Sometimes cells make mistakes when they divide.”

When Genetic Testing Matters Most

The reason these genetic marker tests are so critical for people with NSCLC is that scientists have designed targeted cancer therapies for tumors with these particular gene mutations.

“If we find a tumor mutation, we can treat it with better medication,” Wakelee says. “That’s true now for eight different genes, so it’s very important that tumors are tested before treatment starts, whenever possible.”

In simple terms, these drugs target a protein that is stuck in the “on” position and turn it “off.”

You can take most specific medicines in pill form at home instead of chemotherapy by IV in the hospital. And not only are they more effective, but they’re generally much easier on your system than other cancer treatments, Wakelee says.

When there is a viable gene to target, these therapies shrink tumors more than chemotherapy or immunotherapyand treatment often works longer.

For people with early-stage NSCLC whose tumors are EGFR mutation-positive, treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) afatinib (Gilotrif), erlotinib (Tarceva), gefitinib ( Iressa) and osimertinib (Tagrisso), is generally preferred over standard chemotherapy and immunotherapy.

However, small cell lung cancer has no approved targeted therapies yet. clinical trials continue to explore the possibility.

before deciding

It’s important to wait until you get all the results before making any decisions, Wakelee says.

Along with your panel of genetic tests (sometimes called “molecular tests”), your doctor should test for another biomarker called PD-L1. Levels of this protein suggest whether you are more likely to respond to treatment with immunotherapy drugs

That can make things more complicated, Wakelee says, because the PD-L1 results usually come in much earlier than the mutation results.

A high PD-L1 often means immunotherapy can be successful.

“And it’s tempting to just act on it,” Wakelee says. But that’s not always the best route. If you have certain mutations, such as EGFR, immunotherapy could do more harm than good. And it could make future targeted therapies more toxic to your system.

That is just one example of the possible complications. In some cases, there are so many complex tumor factors that your health care team will meet with a group called a molecular tumor board made up of a combination of:

• expert doctors
• medical oncologists
• surgeons
• Radiation therapists
• researchers
• geneticists
• pathologists

“For someone newly diagnosed with stage IV lung cancer, waiting can be incredibly stressful,” says Wakelee. “Most people want to start treatment right away. But it’s really important to wait to get the full story about the tumor to understand the best option.”

It’s not just about smoking

There can be an ugly stigma that if you get lung cancer, it must have been caused by smoking. That’s unfortunate and untrue, says Yasir Y. Elamin, MD, a chest physician. medical oncologist and assistant professor of thoracic medical oncology at the University of Texas MD Anderson Cancer Center.

Smoking remains the biggest risk factor for the disease (outside of age). But up to 1 in 5 people who die of lung cancer each year have never smoked. That puts lung cancer near the top of the list of the most fatal cancers in the US in people who have never smoked.

“I don’t think anyone deserves to get lung cancer, whether they are a smoker or a non-smoker. But I think we need to understand more and more that lung cancer is not a disease exclusively related to smoking,” says Elamin.

That’s particularly true for lung cancers that respond to targeted therapy.

“For the most part, they’re not related to smoking.” says Elamin. “I think it’s a very painful reminder that lung cancer isn’t just related to smoking. So hopefully it will help us remove some of the stigma around that.”

The future of targeted therapies

Targeted therapies can improve quality of life with fewer side effects and better results. But there are frustrations with these treatments. One of them is that people tend to develop a resistance to them.

“It’s one of the sad realities of targeted therapy,” says Elamin.

It may take 2 or 3 years, but eventually, virtually all people taking targeted therapies develop resistance, especially those who start treatment late in the disease. Much new research is concentrating on how to overcome this problem.

“We are focusing on how and why resistance develops,” says Elamin.

The hope is to find ways to delay or overcome resistance, or better yet, prevent it.

Overall though, Elamin has high hopes. He points to a study of the drug alectinib (alecensa), a targeted therapy for the ALK biomarker. The research found that more than 60% of people with late-stage NSCLC who took the treatment lived for at least 5 more years.

“Imagine the difference,” he says. “When I was doing my training, the 5-year survival for the same group was 5-6%. Is incredible.”

Of course, 60% is not the goal, but Elamin remains encouraged.

“We hope to have it at 90% or 100% one day. But I think we have made progress and, in this case, the numbers speak for themselves.”