Drug Targeting Organ-Specific Strategies

8 Strategies for Specific Drug Targeting
to Tumour Cells
Jos G. W. Kosterink, Wijnand Helfrich, Lou F. M. H. de Leij
8.1 Introduction
Cancer is the second most common cause of death among adults in most Western countries.
Great progress has been made in the treatment of selected malignancies and approximately
50% of all malignancies can be cured by current treatment strategies. The majority of these
cures are achieved by surgery, that is if the disease has not spread throughout the whole body.
Radiotherapy and chemotherapy used alone or in combination have greatly improved the
management of patients with a variety of solid and haematologic malignancies. Chemotherapy
has curative potentials in patients with various haematologic malignancies, testicular
cancer and germ cell tumours. Despite improvements in the treatment of most metastatic solid
tumours, these remain largely incurable. Reasons for this are insufficient tumour selectivity
of anti-cancer agents and poor penetration within the tumour mass [1,2]. Another problem
is that after surgical removal of the solid tumour, metastatic cells that are resistant to
conventional chemotherapy often remain. The same holds for tumours with high metastatic
capacity and high proliferation rates, even though these might be sensitive initially to chemoor
radiotherapy. Relapse may occur with therapy-resistant recurrences. New therapeutic approaches
are under investigation to address these obstacles.
The purpose of this chapter is to describe briefly the pathology of cancer, the cell types involved
in cancer disease, the currently available therapeutics and problems/hurdles to tumour-directed
drug delivery/targeting.The following will be discussed in more detail: surface
epitopes for targeting, molecular targets within the cells for therapeutic intervention, suitable
targeting devices, drugs of choice for targeting and in-vitro and in-vivo techniques which are
available to study the various approaches. Finally the current clinical experience with targeted
anti-cancer drugs will be discussed.
8.2 Cancer Pathology
8.2.1 Cell Biology of Cancer
Drug Targeting Organ-Specific Strategies. Edited by G. Molema, D. K. F. Meijer
Copyright © 2001 Wiley-VCH Verlag GmbH
ISBNs: 3-527-29989-0 (Hardcover); 3-527-60006-X (Electronic)
In the cell cycle, dividing cells undergo one mitosis (M) after another, passing through G 1,S
(DNA synthesis phase), and G 2 phases. Some cells leave the cycle temporarily, entering a G 0
state from which they can be rescued by appropriate mitogenic stimuli. Other cells leave the
cycle permanently, entering terminal differentiation.