Once monoclonal antibodies for a given substance have been produced, they can be
used to detect the presence and quantity of this substance, such as in a:
- Western blot test (used to detect a protein on a membrane of a cell or within the cell itself).
- Immunofluorescence test (used to detect a substance inside a cell).
Different Classes of Targeted Therapies
Within the two categories of small molecules and monoclonal antibodies are different
classes of targeted therapies. The names of the major classes of targeted therapies
typically include the word "anti-" or "inhibitor", together with the name of the target
itself, which means that the drug used blocks that particular target.
It is important to realize that a single drug can have several names, including a generic
name and a brand name. This can be confusing, because the generic and brand names
are used interchangeably in the literature and by the media. We will list the brand
name first often followed by the generic name.
Tyrosine Kinase Receptor Inhibitors
A tyrosine kinase receptor is a molecular structure or site on the surface of a cell that
binds with substances such as ligands. Hormones, antigens, drugs, growth factors and neurotransmitters are examples of ligands. Ligands function as cell signaling molecules by binding to receptors on the surface of the cell. Receptors and ligands are necessary for the cells to function and interact with it's environment.
When the receptor binds with one of these ligands, a chemical reaction
occurs which, in turn, triggers a series of reactions inside the cell. These reactions ultimately influence
cell division, survival, growth, maturation, death, and migration.
These pathways are critical for normal cell activity and are very well regulated by the body. In tumor cells, regulation necessary for normal activity has been altered, the pathways become abnormally triggered which then allows tumor cells to survive, thrive,
and spread all over the body. The goal of blocking the receptor is to prevent the cascade
of reactions and, thus, prevent tumor survival.
- Gleevec (Small Molecule),
generic name - Imatinib
Gleevec, for example, is tailored to halt
the action of an abnormal, cancercausing
protein in chronic myeloid
Image and explanation courtesy of Ohio State
(1) This protein is called Bcr-Abl.
(2) It first binds with a molecule of ATP,
which transfers the energy to the cancer
(3) The activated Bcr-Abl then binds with a signaling protein, GRB-2, and transfers its
energy to that molecule.
(4) Gleevec is designed to bind with Bcr-Abl, which keeps out the ATP and inhibits the
activation of GRB-2.
Gleevec was the first member of a new class of agents that act by inhibiting particular
tyrosine kinase enzymes, instead of non-specifically inhibiting rapidly dividing cells.
Gleevec received FDA approval in May 2001. That same month, it made the cover of
TIME magazine as the "magic bullet" that could cure cancer.
EGFR (HER1/neu) inhibitors
The epidermal growth factor receptor EGFR (ErbB-1, HER1 in humans) is the cell-surface
receptor for members of the epidermal growth factor family (EGF-family) of extracellular
Mutations that lead to EGFR overexpression (known as upregulation) or overactivity have
been associated with a number of cancers, including lung, colon, anal and glioblastoma
multiforme. Mutations, amplifications or misregulations of EGFR or family members are
implicated in about 30% of all epithelial cancers.
The identification of EGFR as an oncogene has led to the development of anticancer
therapeutics directed against EGFR, including gefitinib and erlotinib for lung cancer, and
cetuximab for colon cancer.
- Iressa (Small Molecule) - generic name Gefitinib
- Tarceva (Small Molecule) - generic name Erlotinib
- Erbitux (monoclonal antibody) - generic name Cetuximab