Targeted therapy represents a significant advancement in cancer treatment. This approach focuses on specific molecules involved in cancer cell growth, aiming to disrupt their activity. The Epidermal Growth Factor Receptor (EGFR) is a common and impactful target in certain cancers. This strategy specifically attacks cancer cells while minimizing harm to healthy cells.
Understanding EGFR and Its Role in Cancer
The Epidermal Growth Factor Receptor (EGFR) is a protein on the surface of many cells. Its normal function involves receiving signals from growth factors, telling the cell to grow, divide, and survive. This process is tightly regulated in healthy cells, ensuring controlled tissue development and repair.
In certain cancers, mutations occur within the EGFR gene. These mutations alter the receptor’s structure, causing it to become constantly active, even without external growth signals. This continuous “on” signal leads to uncontrolled cell proliferation and survival, hallmarks of cancer development. Identifying these specific mutations is a foundational step in identifying suitable targets for therapy.
How EGFR Targeted Therapies Work
EGFR targeted therapies block the abnormal signaling pathway initiated by mutated EGFR proteins. These medications bind directly to the EGFR protein, preventing it from sending growth signals inside the cell. This effectively “shuts off” the faulty switch that drives uncontrolled cell division. Unlike traditional chemotherapy, which broadly attacks all rapidly dividing cells, EGFR inhibitors selectively target cells with the specific mutated receptor, leading to fewer side effects on healthy tissues.
These therapies have progressed through different generations, each designed to improve effectiveness and overcome resistance. First-generation inhibitors, such as gefitinib and erlotinib, directly block the receptor’s active site. Second-generation inhibitors, like afatinib and dacomitinib, bind more strongly and irreversibly. Third-generation drugs, including osimertinib, were developed to address common resistance mutations that can emerge during treatment with earlier generations.
Applications and Patient Selection
EGFR targeted therapy is predominantly used in non-small cell lung cancer (NSCLC). For these therapies to be effective, patients must undergo biomarker testing to determine if their tumor harbors certain EGFR gene mutations. Common activating mutations that predict a positive response include deletions in exon 19 and the L858R point mutation in exon 21. These mutations are found in about 10-15% of NSCLC patients in Western populations and up to 50% in East Asian populations.
Testing for these EGFR mutations is performed on tumor tissue obtained through a biopsy, or using a liquid biopsy, which analyzes tumor DNA circulating in the blood. Identifying these mutations ensures the therapy targets the specific molecular abnormality driving the cancer, maximizing treatment success. The presence of other mutations, such as the T790M resistance mutation or exon 20 insertions, also influences treatment decisions, often guiding the selection of different generations of EGFR inhibitors.
Managing Side Effects and Resistance
While generally better tolerated than conventional chemotherapy, EGFR targeted therapies can still cause specific side effects. Common adverse reactions include skin rash, often resembling acne, and diarrhea. Other side effects include changes to nails, such as brittleness or inflammation around the nail bed. These side effects are related to the EGFR protein’s role in healthy skin and gut cells, and their management often involves topical creams, anti-diarrheal medications, and supportive care.
Despite initial effectiveness, cancer cells can develop mechanisms of resistance over time, making the therapy less effective. A common acquired resistance mechanism is the T790M mutation, emerging during treatment with first or second-generation EGFR inhibitors. Newer, third-generation drugs like osimertinib were designed to overcome this particular resistance mutation. Other resistance mechanisms, such as MET amplification or new EGFR exon 20 insertions, can also occur, prompting ongoing research into subsequent treatment strategies.