Lung cancer is characterized by uncontrolled cell growth in the lung tissues. One specific subtype is driven by changes in a protein called the Epidermal Growth Factor Receptor (EGFR). Genetic mutations can affect this protein, leading to the development of cancer. The incidence of lung cancer with EGFR mutations is notably higher among individuals of Asian descent compared to other ethnic groups.
The EGFR Gene and Lung Cancer
The EGFR gene holds the instructions for creating the Epidermal Growth Factor Receptor protein, which sits on the surface of cells. Its normal job is to help cells grow and divide in a controlled manner when it receives specific signals. However, certain mutations can damage this gene, causing the EGFR protein to become stuck in an “on” position, leading to continuous signals for cells to multiply and resulting in uncontrolled growth.
These activating mutations are most frequently found in a type of lung cancer called non-small cell lung cancer (NSCLC), and more specifically, in a subtype known as adenocarcinoma. NSCLC accounts for the majority of lung cancer cases, and adenocarcinoma is its most common form. EGFR mutations are often identified in individuals who are non-smokers or have a history of light smoking, a fact that highlights that the biological drivers of lung cancer can vary significantly.
Prevalence in Asian Populations
A significant observation in the study of lung cancer is the differing prevalence of EGFR mutations across ethnic groups. In patients of East Asian descent with NSCLC, these mutations are found in approximately 40-50% of cases. This figure stands in contrast to the 10-15% prevalence seen in Western populations with the same type of lung cancer, pointing towards a strong ethnic predisposition.
The exact reasons for this higher frequency are still being investigated, but evidence suggests a link to inherent genetic factors, known as germline variations, that are more common within Asian populations. While environmental factors like indoor coal burning and cooking fumes have been considered as potential contributors, the primary driver is believed to be genetic susceptibility. This is supported by genome-wide association studies that show notable differences in the genetic architecture of NSCLC between Asian and non-Asian individuals.
Diagnosis and Molecular Testing
The diagnosis of EGFR-mutated lung cancer begins after an initial cancer diagnosis, typically made through imaging scans like CTs, followed by a biopsy. During a biopsy, a small sample of the tumor tissue is removed for examination. This tissue is then sent for molecular or genomic testing to look for specific genetic alterations, including mutations in the EGFR gene.
The standard method for this testing is the analysis of the tumor tissue itself. However, a less invasive method known as a liquid biopsy is also available. A liquid biopsy tests for fragments of cancer DNA, called circulating tumor DNA (ctDNA), that are shed from the tumor into the bloodstream. Identifying the presence of an EGFR mutation and determining its specific type, such as an exon 19 deletion or an L858R point mutation, provides information needed to select the most effective treatment.
Targeted Therapy Treatments
The discovery of EGFR mutations has revolutionized treatment for this type of lung cancer through an approach called targeted therapy. These treatments interfere with the specific molecules, or “targets,” involved in the growth and spread of cancer cells. For EGFR-mutated lung cancer, the primary therapy involves drugs known as EGFR inhibitors or tyrosine kinase inhibitors (TKIs), which work by blocking the signals sent by the mutated EGFR protein.
This action can be compared to turning off a light switch that is stuck in the “on” position, thereby halting or significantly slowing the cancer’s growth. This approach is different from traditional chemotherapy, which affects all rapidly dividing cells in the body. As a result, EGFR inhibitors often have a different set of side effects that can be more manageable. Common examples of these oral medications include osimertinib, gefitinib, and erlotinib.
Prognosis and Acquired Resistance
For patients with advanced EGFR-mutated lung cancer, the development of targeted therapies has led to a more favorable prognosis compared to other types of advanced lung cancer. These treatments can control the disease effectively, often for many months or even years, by targeting the cancer’s driving mechanism. This allows many patients to maintain a good quality of life.
A challenge in the long-term management of this disease is the development of acquired resistance. Over time, cancer cells can evolve and develop new mutations that allow them to evade the effects of the EGFR inhibitor. The most common of these resistance mechanisms is a secondary mutation known as T790M. When a treatment starts to become less effective, a new biopsy is often performed to identify the cause of resistance, which can then guide the next steps in treatment.