Understanding Lung Cancer Part 2: Driver Mutations and Tumor Growth

By Matthew Reiss, MSE, PhD, Manager, Precision Medicine & Navigation, GO2 for Lung Cancer

This is the second blog post of our ongoing “Understanding Lung Cancer” series, which aims to simplify the science behind lung cancer and help provide a deeper understanding of the disease. In the first blog post of our series, we introduced the basics of cells, DNA, and how damage to DNA can lead to cancer. This time, we’ll take a closer look at the specific changes or mutations that cause lung cancer to grow, and explore how tumors form and spread over time. 

What are “driver mutations”? 

Not all mutations are harmful or lead to cancer. Often, cells catch and fix small mistakes in their DNA before they cause problems. Other times, if the damage is too great, the cell will self-destruct to prevent the mistake from causing problems. But when a mistake slips past the cell’s defenses and affects certain important genes, the cell may keep dividing and pass the change on to new cells. Over time, this leads to cancer.   

These changes in important genes are called driver mutations because they “drive” the development and growth of cancer. Think of it like a car with a stuck gas pedal or brakes that don’t work—driver mutations make cells grow and divide when they should stop. 

Common driver mutations in lung cancer 

There are many different kinds of driver mutations in lung cancer. Some of the most common ones happen in genes like: 

• ALK (Anaplastic Lymphoma receptor tyrosine Kinase)  

• BRAF (Rapidly Accelerated murine Fibrosarcoma viral oncogene homolog B)  

• EGFR (Epidermal Growth Factor Receptor)  

• KRAS (Kirsten RAt Sarcoma viral oncogene homolog)  

Normally, these genes help control cell growth. But if the DNA that makes these genes become damaged, it can send the wrong signals—telling the cell to grow out of control. 

How tumors grow 

When a cell has a driver mutation, it may begin to act differently and divide more than it should. In healthy cells, “stop and go” signals tell cells when to grow and when to stop, but in cancer cells, these signals are ignored. 

As abnormal cells keep dividing, they form a lump of tissue called a tumor. In lung cancer, tumors often start forming in the lining of the airways. As they continue to grow, the tumor may: 

• Grow large enough to press on the nearby structures of the lung 

• Damage healthy lung tissue 

• Cause symptoms like coughing or shortness of breath 

Over time, some cancer cells may begin to break away from the original tumor and travel through the bloodstream or lymphatic system to other parts of the body—like the brain, bones, or liver— and start growing new tumors. When cancer has spread like this, it’s called metastasis, and it can make treatment more difficult. 

Why do cancer cells keep growing? 

Cancer cells are sneaky. They find ways to keep growing, even when the body tries to stop them. Some of the ways that cancer cells can keep growing include: 

• Making their own growth signals 

• Blocking signals that would normally cause them to self-destruct 

• Growing new blood vessels to bring in more oxygen and nutrients 

• Developing ways to reduce or hide from the immune system, which would normally destroy the cancer cells 

• Developing new mutations that help them resist treatment 

One size doesn’t fit all

One of the most important things we’ve learned is that not all lung cancers are the same. There are many different types, each with its own set of driver mutations. Even people with changes in the same gene may respond differently to treatment. That’s why learning what is driving a person’s cancer is so important, especially for people with non-small cell lung cancer (NSCLC).  

This is where biomarker testing comes in. Biomarker testing looks for changes in or on cancer cells that make them different from healthy cells. For some people, finding the driver mutation may help their healthcare team choose a treatment that works best for their specific cancer. 

Coming up next: treatment and the immune system 

In the next part of this series, we’ll look at the basics of the new and exciting ways researchers are working to treat lung cancer. We’ll also explore how the immune system helps fight lung cancer.