Chemistry Reference
In-Depth Information
aggressiveness and metastatic capacity of tumor cells as they migrate around the
body [1] .
The difference between surface carbohydrates in normal and tumor cells pro-
vides many possible strategies that can be exploited for the treatment of cancer
and these are summarized in Table 28.1 (see also Chapter 25.2).
Therapies have been developed that use surface carbohydrates on tumor cells
as markers to generate antibodies against the tumor cells. An example of this is
provided by the study of globo-H antigen - a surface carbohydrate found on pros-
tate, colon and human breast tumor cells (see Figure 28.1 for the structure of
globo-H antigen and Chapter 1 for common structural abbreviations). The chal-
lenges associated with preparing carbohydrates of biological and therapeutic inter-
est are discussed in Info Box 1 .
Recently, mice treated with globo-H antigen bound to a protein carrier have
been shown to generate large amounts of antibodies that are capable of recogniz-
ing tumor cells [2]. Monoclonal antibodies generated against tumor-associated
carbohydrate antigens should be able to deliver anticancer drugs to their specifi c
site of action. Thus, it has been possible to increase the therapeutic indices of
anticancer drugs via ligand-mediated targeting of liposomal anticancer drugs.
These liposomes or phospholipid bilayer vesicles can be used to carry drugs that
are either trapped inside their hydrophilic aqueous interiors or associated to their
Table 28.1
Possible carbohydrate-based approaches for the treatment of cancer.
Disease pathway
Therapeutic opportunity
Examples of carbohydrate - based therapies
Biosynthesis of unnatu-
ral carbohydrates on the
tumor surface
Raise antibodies to the tumor-
associated carbohydrate anti-
gens to develop a vaccination
strategy
Carbohydrate antigens on protein carrier for
potential treatment of prostate, colon and breast
cancer; theratope (sialyl-Tn antigen conjugate
vaccine) for metastatic colorectal and breast
cancer
Biosynthesis of unnatu-
ral carbohydrates on the
tumor surface
Use antibodies generated from
the tumor - associated carbo-
hydrate antigens to deliver
agents to cancer cells
Ligand - targeted liposomal therapeutics
Biosynthesis of unnatu-
ral carbohydrates on the
tumor surface
Inhibit the carbohydrate pro-
cessing enzymes
Naturally occurring aza and imino sugars, as well
as synthetic derivatives - inhibition of metastatic
tumors and tumor growth, as well as pulmonary
and colon cancers
Biosynthesis of unnatu-
ral carbohydrates on the
tumor surface
Inhibit the interactions of the
tumor - associated carbohydra-
tes with the lectin receptors,
to minimize metastasis
Multivalent sialyl - Le
x
derivatives, as potential
antimetastatic agents
