Kadcyla networks in the cell. (Barok, Joensuu, Isola 2014)

Kadcyla is a HER2- targeted
antibody drug conjugate (ADC). It works directly inside cancerous cells however
Avastin does not. When Trastuzumab emtansine (T-DM1) binds to HER2 on the
plasmas membrane, it forms a complex of HER2-TDM1 using a stable linker which inserts
itself into the cell by receptor-mediated endocytosis. Avastin however, does not
form a complex on the plasma membrane. The adopted endocytic vesicles then produce
early endosomes. These can either be reutilized and put back to the cell
membrane or they can develop to form a lysosome. Proteolytic degradation of the
antibody fragment of T-DMI in the lysosomes causes DM1 (emtansine) to be
released. To be more specific, DM1-containing catabolites are released which
inhibit microtubule assembly resulting in cell death. When DM1 binds to
tubulin, it disrupts microtubule networks in the cell. (Barok, Joensuu, Isola 2014) Consequently, cell cycle arrest at the
G2-M phase and cell apoptosis occurs. Trastuzumab emtansine inhibits HER2
receptor signalling, mediates antibody-dependent cell-mediated cytotoxicity,
and inhibits shedding of the HER2 extracellular domain in human breast cancer
cells that overexpress HER2. (Google
Books 2018) Both Kadcyla and Avastin cause cell apoptosis. Trastuzumab is
the predominant therapy used for HER2-positive breast cancer. Kadcyla is
clinically proven to be the most effective with metastatic breast cancer (MBC)
and early breast cancer (EBC). In both breast cancers, there has been
improvement in survival rate. (Dubel,
Reichert 2014)