Thought of by most as a silver bullet method
for the treatment of breast cancer, the field of targeted
cancer therapy is developing at a rapid rate, and may soon
become the preferred treatment method for most cancers. The
drugs used block the processes by which normal cells become
cancerous and of tumor growth by interfering with specific
Targeted Therapy: What is it?
Similarly to chemotherapy, targeted therapy is a systemic
treatment, which means that it can affect the entire body.
Usually the drugs are injected into the bloodstream, but unlike
chemotherapy drugs, which non-specifically
attack any dividing cell, targeted drugs will only affect
cells that express the specific target they are made to match.
This means that the effect of targeted drugs on healthy cells
is much less than that of chemotherapy.
Uses of Targeted Therapy
Targeted therapy drugs are designed in laboratories based
upon known genes and proteins involved in various cancers.
Cancerous cells express certain proteins differently than
healthy cells. Scientists have been able to turn these proteins
into molecular targets that can be sensed and locked onto
by the drugs they build. Most of the targets are involved
in one way or another with signaling cell growth and division.
Consequently, most targeted drugs act to block the action
of their targets, thus slowing or reversing tumor growth.
Targeted Therapy Drugs
There are several groups of targeted drugs either currently
in use (approved by the FDA) or available through clinical
research trials. These drugs fall into the categories of monoclonal
antibodies, “small molecule” drugs, and apoptosis
inducing drugs. Each category differs in the way in which
it aims at its target.
Monoclonal antibodies are a family of drugs that recognize
and fasten onto particular targets, like a key in a lock.
They then cause cell death by stimulating either certain internal
signals or an immune system reaction. Herceptin is a monoclonal
antibody used in the treatment of breast cancer. It binds
to a protein called HER-2, which can be over-expressed in
some cancerous cells. By binding, it blocks growth factors
that would lead to cell growth and division. Rituxan is an
antibody used to treat several types of cancers by binding
to CD20, a receptor protein, on the surface of immune cells
called B-cells. This makes the cells susceptible to attack
by the immune system, and may trigger a process of self-destruction
called lysis in which the cell bursts.
“Small-molecule” drugs are also sometimes called
signal transduction inhibitors because they interfere with
abnormal proteins inside cancerous cells that are involved
with cell growth and division. Some normal cells become cancerous
because certain genes that stimulate cell division get turned
on, or their off switch gets broken. Small molecule drugs
target the protein products of these broken genes. Gleevec
is a drug made to block an enzyme called tyrosine kinase that
is necessary for stimulating cell growth. Alternatively, Iressa
blocks a growth factor that would normally stimulate tyrosine
kinase to promote cell growth. These drugs go after different
small molecules in the chain of the signaling pathway that
leads to cell growth.
Apoptosis is a process otherwise known as programmed cell
suicide. Normal cells will start the process of apoptosis
when they sustain enough genetic damage to warrant it. Cancerous
cells will continue to thrive even with significant amounts
of damage to their DNA because the necessary internal controls
are broken or blocked by other signals promoting cell survival.
Apoptosis-inducing drugs act to cause cancer cells to commit
suicide. A drug called Velcade works in this manner by blocking
the actions of proteins called proteasomes, which are significant
to the growth and survival of cells. Genasense blocks the
activity of a protein called BCL-2, which promotes cell survival.
Side Effects of These Drugs
While these drugs produce fewer side effects than shotgun-type
treatments like chemotherapy
and radiation therapy,
negative side effects should still be expected since no method
is perfect and people may react differently. In fact, allergic
reactions are common for people who do experience side effects
during targeted cancer therapy. Doctors prefer to monitor
patients receiving targeted therapy closely because most drugs
available to patients are still in the clinical trial phase.
Doctors are still learning how to use them safely and in combination
with other drugs and how to identify the best patients for
each new drug. With time and experience, targeted therapy
is likely to become a preferred treatment method.
Kirsten Sanford is a science journalist
& PhD candidate in the Molecular, Cellular and Integrative
Physiology Graduate Group at the University of California,
Davis. In addition to developing patient health education
materials she also hosts a weekly science radio show (This
Week in Science) dedicated to bringing current scientific
news and research to the public.