Anticancer Agents - Drug Design and Discovery - page 391

i nding is now routinely used in diagnostics and in the classii cation of patients into groups ame-
nable to Herceptin treatment, which signii cantly benei ts this well-dei ned subpopulation. Today
Herceptin is often part of chemotherapeutic regimens also containing topoisomerase II targeting
anthracyclines, or microtubule targeting paclitaxel in patient populations with highly elevated levels
of HER2 expression, although Herceptin has also been applied as monotherapy, with encouraging
results.

23.3 CONCLUDING REMARKS
In this chapter, we have briel y touched on the molecular and cellular background underlying the
development of cancer. Furthermore, we have focused on some anticancer agents in current clini-
cal use. The six anticancer agents reviewed represent a continuum in cancer drug development
beginning with the antimetabolites used in cancer therapy for more than half a century (Alimta and
Xeloda) over therapy targeting the structural function of the cancer cell (Taxol) as well as its epige-
netics (Zolinza) to novel highly targeted small molecule (Gleevec) and antibody-based (Herceptin)
therapies.
This continuum not only represents a developmental time scale, but also rel ects today's clini-
cal practice, attesting to the fact that in the i eld of cancer treatment old drugs continue to be
used alongside much newer ones. This is because the older anticancer drugs, the cytotoxics, are
generally highly effective although they show their well-known side effects. On the other hand,
while being more cancer specii c, the new targeted therapies are often hampered by their rather
restricted applications (with regard to indication) or lack of efi cacy when administered as single
agents. It is therefore often advantageous to combine the classic cytotoxics with new targeted
molecules. Here, numerous preclinical and clinical research projects are beginning to indicate the
directions toward effective combination regimens including both old and new drugs. We believe
these approaches will be further developed in coming years and several new principles, e.g. in gene
therapy, cancer immune therapy, and stem cell research will i nd their way to the patient, possibly
even as individually tailored personalized medications, but certainly also as traditional add on to
existing therapy.

ABBREVIATIONS
Topo topoisomerase

GRAFT glycinamide ribonucleotide formyltransferase

DHFR dihydrofolic reductase

TS thymidylate synthase

MoAb monoclonal antibody

EGFR epidermal growth factor receptor

VEGF vascular endothelial growth factor

VEGFR vascular endothelial growth factor receptor

FGF i broblast growth factor

TGF transforming growth factor

CD20 nonglycosylated phosphoprotein expressed on the surface of all mature B-cells

MAPK mitogen activated protein kinase

AML acute myeloid leukemia

APL acute promyelocytic leukemia

CTCL cutaneous T-Cell lymphoma

MDS myelodysplastic syndromes

ATAR all trans -retinoic acid