In a healthy state, cell growth, division, and death are precisely regulated. However, when key regulatory pathways malfunction, cells may escape this "command system," proliferating continuously and evading immune clearance, ultimately leading to disease—particularly tumors.

As one of the world's leading malignancies, lung cancer has a complex pathogenesis rooted in the imbalance of cell growth regulatory systems. These imbalances are often genetic. For instance, EGFR point mutations allow the EGFR protein to activate automatically without the need for external ligand stimulation, magnifying downstream signals and leading to uncontrolled cell proliferation.

EGFR is a receptor tyrosine kinase located on the cell membrane that regulates cell proliferation, differentiation, and survival across various tissues.

Under normal conditions, when growth factors bind to EGFR, it triggers receptor dimerization and activates its kinase activity. This initiates a series of downstream signaling pathways (primarily RAS-MAPK and PI3K-AKT), instructing the cell to grow and survive in a regulated, transient manner.

However, when mutations occur in the EGFR gene, especially within the kinase domain, this balance will be broken, which often leads to:

1. Autonomous Proliferation: The MAPK pathway is constitutively activated, driving uncontrolled cell division and rapid tumor growth.

2. Inhibition of Apoptosis: The AKT pathway is abnormally activated, suppressing programmed cell death (apoptosis) and allowing tumor cells to survive under adverse conditions.

3. Enhanced Angiogenesis: By upregulating factors like VEGF, mutations induce the formation of new blood vessels, providing oxygen and nutrients for sustained tumor growth.

4. Signal Addiction: Tumor cells become highly dependent on this abnormally activated EGFR pathway, exhibiting classic "oncogene addiction."

Typical EGFR mutations include exon 19 deletions, the L858R point mutation in exon 21, and others. These mutations are primarily concentrated in the kinase domain of EGFR, directly affecting its kinase activity and signaling patterns.

In response to the abnormal activation state caused by point mutations within the EGFR kinase domain, EGFR-tyrosine kinase inhibitors (EGFR-TKIs), which target this domain, have been progressively developed and applied.

These drugs block abnormal signal transduction by selectively inhibiting the kinase activity of mutant EGFR, cutting off the core driver pathway at the source that tumor cells rely on for survival and proliferation.

While EGFR-TKI treatment strategies have been established, research surrounding EGFR point mutations continues to deepen, currently focusing on three levels:

1. Mutation detection and typing: With the help of high-throughput sequencing and high-precision gene editing models, researchers can accurately identify different EGFR point mutations and their functional differences.

2. Functional mechanism analysis of mutations: Through cellular and animal models, researchers analyze how point mutations alter EGFR structure, kinase activity, and downstream signaling networks.

3. Research on targeting and resistance mechanisms: Developing targeting strategies based on mutant structures and continuously exploring new mechanisms related to secondary mutations and drug resistance.

The common goal of these studies is to start from "a change in a single gene" to establish a more refined and controllable understanding of the disease.

EDITGENE has launched various EGFR-related gene-edited cell line models to provide stable and reliable tools for studying disease and drug resistance mechanisms.

Point Mutation Cell Line