1.2.4. The Anticancer Drug’s Targets

• (a) Enzymes - Antimetabolites

• (b)Hormones - Androgens, Oestrogens, Progestins, LHRH agonists, Antioestrogens, Antiandrogens

• (c) Nucleic Acids - Intercalating agents, alkylating agents, chain cutters

• (d) Structural proteins

• (e) Signaling pathways

1.2.5. Mechanism of Action of Anticancer Drugs

The majority of anticancer drugs affect cell division or DNA synthesis and function. Many of them also work on interacting with RNA or protein. The DNA interacting drugs can be classified as alkylating agents, antimetabolites, anticancer antibiotics, mitotic inhibitors and plant alkaloids. Some chemotherapeutics do not directly interact with DNA, but target molecular abnormality in certain types of cancer. Furthermore, some drugs are used to modulate cancer cell behavior, without directly attacking, like in the hormone treatment.

Development of new efficient anticancer drugs needs a detailed knowledge of the mechanism of drug action at the cellular and molecular levels. Since most anticancer drugs shows their activity through the interaction with DNA, extensive research efforts in this field have culminated in useful information about DNA structure, dynamics and DNA-drug interactions.  There are several ways of interaction between DNA/RNA/protein and a drug and they can be classified as follows

(a) Block nucleic acid (DNA, RNA) biosynthesis: Antimetabolites

• • Folic Acid Antagonist: inhibit dihydrofolate reductase (methotrexate)

• • Pyrimidine Antagonist: inhibit thymidylate synthetase (fluorouracil) ; inhibit DNA polymerase (cytarabine)

• • Purine Antagonist: inhibit interconversion of purine nucleotide (mercaptopurine)

• • Ribonucleoside Diphosphate Reductase Antagonist: (hydroxyurea) 

(b) Directly destroy DNA and inhibit DNA reproduction

• • Intercalating agents, alkylating agents, chain cutters-Antibiotics

(c) Interfere transcription and block RNA synthesis

• • Bind with DNA to block RNA production: doxorubicin

(d) Interfere protein synthesis and function

• • Antitubulin: vinca alkaloids and taxanes;

• • Interfere the function of ribosome: harringtonines

• • Influence amino acid supply: L-asparaginase

• • Bind tubulin, destroy spindle to produce mitotic arrest.

(e) Influence the Structure and Function of DNA

• • Alkylating Agent: mechlorethamine, cyclophosphamide and thiotepa

• • Platinum: cis-platinium

• • Antibiotic: bleomycin and mitomycin C

• • Topoismerase inhibitor: camptothecine and podophyllotoxin

(f) Influence hormone homeostasis: These drugs bind to hormone receptors to block the actions of the sex hormones which results in inhibition of tumor growth.

• • Estrogens and estrogen antagonistic drug

• • Androgens and androgen antagonistic drug

• • Progestogen drug

• • Glucocorticoid drug

• • gonadotropin-releasing hormone inhibitor: leuprolide, goserelin

• • aromatase inhibitor: aminoglutethimide, anastrazole