186
Cancer Chemotherapy, Theoretical Foundations of
through which the inhibitor regulates can-
cer cell growth and the expression of these
targets in the particular cancer type. In
this respect, we have already discussed the
different properties of Hsp90 inhibitors
in apoptosis and cell cycle arrest, and
how these properties could impact on the
clinical regimen and perhaps require pa-
tient stratiFcation for maximum clinical
beneFt.
The
possibility
of
resistance
to
mechanism-based agents remains to be
determined. Tumor cells are adept at
acquiring
drug
resistance
phenotypes
through diverse mechanisms, and we
have
already
seen
clinical
resistance
to
Gleevec,
but
we
await
further
information before this becomes clinically
exempliFed for other new agents. Of
course, if drug resistance does appear
as a clinical hurdle, then it may be
possible
to
modulate
its
progression
by
altering
drug
concentration
and
exposure through a combination therapy
approach.
It is clear that many questions remain
to be answered. Nevertheless, we are wit-
nessing an exciting era in cancer drug
discovery in which newer drugs are be-
ginning to replace conventional cytotoxic
approaches. Our views and anticipations,
which are shared by many others, reflect
the gathering momentum that translat-
ing research knowledge about the cancer
cell will yield improved and more ef-
Fcacious drugs for treating the cancer
patient.
Acknowledgment
We thank Marie Caldwell for help in
preparing the manuscript. Work in our
laboratory was supported by the MRC,
CRUK, LR±, AICR and EC.
See
also
Bioorganic
Chemistry;
Drug Bioavailability, Distribution
and Clearance Prediction; Medic-
inal Chemistry.
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