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Lapatinib is a tyrosine kinase inhibitor primarily used in the treatment of HER2-positive breast cancer, among other cancer types. Its mechanism of action involves binding to the intracellular ATP-binding sites of the HER1 (also known as EGFR) and HER2 receptors, thereby inhibiting their autophosphorylation and subsequent activation of downstream signaling pathways. The major pathways involved include:
-PI3K/AKT/mTOR Pathway
Inhibition of this pathway leads to reduced cell survival and proliferation, as it normally promotes growth and survival signals through downstream effectors.
-RAS/RAF/MEK/ERK (MAPK) Pathway
Blocking the activation of this cascade affects cell cycle progression, proliferation, and differentiation. In many cancers, dysregulation of this pathway contributes to uncontrolled growth.
By interfering with these signaling cascades, lapatinib can reduce tumor cell proliferation, induce apoptosis (programmed cell death), and potentially increase the sensitivity of tumor cells to additional therapeutic agents.
The induction of oxidative stress is one of the ways by which lapatinib can exert cytotoxic effects on cancer cells. Elevated ROS levels can damage cellular components, such as lipids, proteins, and DNA, thereby contributing to cell death.