For
instance, a clinical study shows that
agent A helps 60 leukemia patients out
of 100 to keep their disease in check,
or, as it is usually said, to achieve
complete remission. With agent B, complete
remission is seen in 35 patients while
with agent C complete remission is achieved
in 5 patients. Thus, oncologists selecting
between agent A, agent B, and agent C,
would rather use agent A because agent
A is expected to be effective in 60% of
leukemia patients. What about the remaining
40% of patients who are statistically
not expected to respond to agent A, but
would better benefit from agent B or agent
C? For them, the use of agent A will result
in treatment failure. In other words,
their tumor cells will not be killed effectively
enough, complete remission will not be
achieved and the disease will progress.
It may be reasonable for patients in this
group to utilize agent B or agent C after
agent A fails. Unfortunately, it is not
always possible to use another treatment
protocol with the same patient. First,
all chemotherapeutic agents are highly
toxic substances and patients may not
survive another round of treatment. Besides,
time is lost and the disease may progress
beyond its treatable phase. To complicate
the picture, it is unclear whether the
patient’s tumor cells would be
more sensitive to agent B or agent C.
The
American Cancer Society estimates that
approximately 1.22 million new cancer
cases are diagnosed every year. For more
than 700,000 of these patients, some form
of chemotherapy will be used in the treatment
plan.
The
treatment outcome for cancer patients
could be dramatically improved if oncologists
would include agents that are effective
against tumor cells of a specific patient
in the first line of therapy.
The
Microculture Kinetics (MiCK) assay for
apoptosis helps oncologist discriminate
between effective and ineffective chemotherapeutic
agents prior to their use in a patient’s
treatment. MiCK assay helps oncologists
to create an individual treatment protocol
that includes a drug or drug combination
that is most effective in killing tumor
cells of an individual patient.
How
does MiCK assay work? Over the last 10
years it has been shown in multiple studies
that chemotherapeutic agents exert their
antitumor activity by triggering apoptosis,
a distinct mode of cell death that is
accompanied by dramatic changes in the
appearance of tumor cells.
The
figure above is a photomicrograph of a
“healthy” tumor cell (at
left) and three other tumor cells at various
stages of apoptotic death cased by exposure
to a chemotherapeutic agent. The photo
demonstrates that cells dying by apoptosis
form big blebs on the outer surface of
the cell. Formation of these blebs results
in a change in the cells’ light
scattering properties. A sophisticated
device called a spectrophotometer can
detect the resulting change in the optical
properties of apoptotic cells.
Tumor
cells undergoing apoptosis manifest an
increased side light scattering as compared
to “healthy” tumor cells.
The MiCK assay of apoptosis is based on
frequent measurements of the optical density
of tumor cells exposed to multiple chemotherapeutic
agents. If a chemotherapeutic agent kills
tumor cells by apoptosis, the spectrophotometer
will “see” and report accumulation
of apoptotic tumor cells as a steep increase
in the optical density. On the computer
screen, this steep increase in the optical
density appears as a so called “apoptotic
curve”. Data generated by the
spectrophotometer are fed to the computer
and automatically analyzed in order to
determine the extent of the tumor cells’
apoptosis. This allows for the identification
of a chemotherapeutic agent which causes
the most extensive apoptosis in tumor
cells. If a patient has no medical contraindications,
this agent may be included in the patient’s
treatment protocol.
In
no way can MiCK assay’s results
substitute for the medical judgment of
an oncologist. The MiCK assay is a powerful
tool arming oncologists with valuable
information on the drug sensitivity profile
of a specific cancer patient. However,
the final decision on whether a specific
agent should or should not be included
in the patient’s treatment protocol,
is always made by the patient’s
physician.