Biology of Disease

Drug Examples of clinical use

5-FU breast and GIT cancers

Ara-C acute leukemia

6-MP acute myeloid leukemia

acute lymphoblastic leukemia.

6-TG acute myeloid leukemia

acute lymphoblastic leukemia.

Table 17.8Purine and pyrimidine analogs in cancer treatment

Figure 17.28Structures of (A) paclitaxel (taxol) and (B) docetaxel (taxotere).

Pt

NH 3

Cl NH 3

Cl

Cisplatin

Pt

NH 3

O NH 3

O

O

O

C

C

Carboplatin

Pt

NH 2

O NH 2

O

O

O

C

C

Oxaliplatin

A)

Figure 17.29(A) Structures of the platinum-

based anticancer drugs, cisplatin, carboplatin and

oxaliplatin. (B) A molecular model of cisplatin

bound to DNA. Note how the double helical

structure has been bent and distorted by the

binding of the drug. PDB file 1A84.

X]VeiZg&,/ CANCER

).+ W^dad\nd[Y^hZVhZ

Cisplatin (cis-diamminedichloroplatinum) was first discovered in experiments

that showed that the growth of bacteria was inhibited by an electric current

delivered by platinum electrodes. This drug is now used in combination

therapy to treat testicular cancer. It is also used in treating lung cancer. Other

platinum-based drugs include carboplatin and oxaliplatin and all function

by binding to DNA, cross-linking the strands and distorting its double helical

shape (Figure 17.29 (A) and (B)). This facilitates the binding of other proteins

to the DNA molecule that mediate toxicity of the drug.

Tumor-specific molecules, on the surfaces of cancer cells may be targeted

with monoclonal antibodies (Chapter 4). In this way treatment should be

more directed at the tumor and general toxicity reduced. Over the years,

several approaches have been made to producing targeted therapy using these

(H 3 C) 3 C

N

O

O

O

O

O

O

O

O

O

OH

OH

O OH

H

H

O

CH 3

CH 3

CH 3

CH 3

CH 3

CH 3

A)

N

O

O

O

OH

O

O

O

O

O

OH

OH

OH

O

O

H

H

CH 3

CH 3

CH 3

CH 3

CH 3

B)