Several
companies offer commercial testing of the
drug- resistance of tumor cells. The
majority of them utilize the following assays
or their modifications:
- Clonogenic
Assay (Puck & Marcus, 1956): relies
on the proliferation of tumor clonogenic
cells surviving drug exposure.
- Nucleic
Acid Precursor Incorporation (Cline &
Rosenbaum, 1968): relies on the incorporation
of a radionuclide by tumor cells surviving
drug exposure.
- Differential
Staining Cytotoxicity Assay (Weisenthal
et al, 1983) (a variant of the DiSC assay
is also known as EVA™): relies on intactness
of the cell membrane of tumor cells surviving
drug exposure.
- MTT
Assay (Mossman, 1983): relies on the enzymatic
reduction of tetrazolium salt by tumor cells
surviving drug exposure.
As
a group, all these assays are referred to
as cell growth-based assays because
they measure a fraction of tumor cells surviving
exposure to a chemotherapeutic agent. Cell
growth-based assays were designed and are
being used to detect drug resistance
of tumor cells.
In order to detect drug sensitivity
of tumor cells, one must use a cell death-based
assay, i.e. an assay that would measure
a fraction of tumor cells killed by a chemotherapeutic
agent.
Chemotherapy is known to kill tumor cells
via two major mechanisms: necrosis and apoptosis.
High doses of chemotherapy induce in cells
necrotic death while mild, therapeutic doses
induce apoptotic death. Multiple studies have
demonstrated that chemotherapeutic agents
exert their therapeutic effect by inducing
apoptosis in the drug-sensitive tumor
cells.
An assay that measures a specific form
of the drug-induced cell death - APOPTOSIS
- is required to determine clinically relevant
drug sensitivity of the tumor cells.
Cell
growth-based drug resistance assays do not
measure apoptosis and, thus, cannot be used
to determine directly drug sensitivity of
the tumor cells.
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DiaTech’s
Advanced Technology
The
ultimate goal of cancer chemotherapy is killing
of tumor cells. There are two major mechanisms
by which a chemotherapeutic agent can kill
tumor cells. These mechanisms are apoptosis
and necrosis. When administered in
mild, clinically relevant doses, chemotherapeutic
agents kill drug-sensitive tumor cells
via mechanism of apoptosis.
When
a cancer patient's specimen is submitted for
the drug sensitivity study, the referring
oncologist wants to know which chemotherapeutic
agent is the most effective in inducing apoptosis
in the patient's tumor cells. This information
would tell the physician to which drug an
individual cancer patient's tumor cells are
the most sensitive.
To
establish a drug sensitivity profile
of tumor cells, DiaTech Oncology utilizes
a unique, proprietary technology called the
Microculture
Kinetic (MiCK) assay for apoptosis. The
MiCK assay is designed to automatically detect
and report drug-induced apoptotic death
of tumor cells. Based on the MiCK assay results,
DiaTech Oncology provides a physician with
clinically relevant drug sensitivity profile
of tumor cells of an individual cancer patient.
