Osimertinib, known by its brand name Tagrisso, is a targeted therapy for a specific type of lung cancer. It is primarily used in treating non-small cell lung cancer (NSCLC) with particular genetic alterations. The drug precisely interferes with the mechanisms that drive the growth of these cancer cells.
The Target of Osimertinib
The biological target of osimertinib is the Epidermal Growth Factor Receptor (EGFR) protein. Normally, EGFR sits on the surface of cells, receiving signals that tell the cell to grow and divide in a controlled manner.
However, in certain lung cancers, mutations in the EGFR gene cause the receptor to become permanently active, like a gas pedal stuck in the “on” position. This constant activation sends unchecked “grow” signals, leading to uncontrolled cell division and tumor formation. The most common sensitizing mutations are deletions in exon 19 and a point mutation called L858R in exon 21, which account for approximately 90% of mutations in NSCLC.
The Process of Inhibition
Osimertinib functions as a Tyrosine Kinase Inhibitor (TKI). Once inside the cancer cell, it specifically seeks out the mutated EGFR protein. The drug forms an irreversible bond within the ATP-binding site of the EGFR kinase domain.
This binding action physically blocks the site where adenosine triphosphate (ATP), the cell’s energy molecule, would normally attach. By occupying this site, osimertinib prevents the mutated EGFR from utilizing ATP to send continuous growth signals. This interruption effectively shuts down the signaling pathways responsible for driving cancer growth.
Overcoming Acquired Resistance
A challenge with earlier generations of TKIs was the development of acquired resistance. A frequent cause is the emergence of a secondary EGFR gene mutation, specifically T790M. This T790M mutation alters the ATP-binding pocket, reducing the ability of older drugs to bind effectively.
Osimertinib was designed to overcome this resistance. It inhibits EGFR even when the T790M resistance mutation is present. This ability makes osimertinib a therapeutic option for patients who have progressed on prior EGFR TKI therapies, and increasingly, as an initial treatment.
Unique Therapeutic Properties
Osimertinib possesses distinct properties that enhance its effectiveness in treating lung cancer. It has high selectivity for mutated EGFR over normal EGFR found in healthy cells. This selective targeting helps reduce unwanted side effects on healthy tissues, which are often observed with less selective inhibitors.
Another property is its ability to penetrate the central nervous system (CNS). Osimertinib can cross the blood-brain barrier, a protective filter that restricts many drugs from entering the brain. This capability allows the medication to reach and act on lung cancer cells that may have spread to the brain, known as brain metastases. Treating or preventing the growth of these brain metastases is a significant advantage, as brain involvement is a common and serious complication of advanced lung cancer.