Chemotherapeutic Drugs for Cancer

Anticancer drugs are classified based on two major categories depending on cell cycle action as follows.

• Cell cycle specific drugs: Anti-metabolites, drugs targeting topoisomerase and anti tubulin agents
  • S phase: Antimetabolites, epipodophyllotoxins, bleomycin, camptothecins
  • G2 phase: Epipodophyllotoxins, bleomycin
  • M phase: Taxanes, Vinca alkaloids
• Cell cycle nonspecific drugs
  • Nitrogen mustards
  • Alkyl alkane sulfonates
  • Actinomycins
  • Anthracenediones
  • Nonclassic Alkylating agents
  • Aziridines
  • Nitrosourea

I. Alkylating agents: First therapeutic agent used for the treatment of cancer is Alkylating agent. They form covalent bonds with alkyl groups. They also cross links with DNA thereby damaging DNA template and stopping DNA synthesis. They act as carcinogenic, teratogenic and cytotoxic agents. There are two types of alkylating agents as follows

• Classical alkylating agent
  • Nitrogen mustards
    • Mechlorrethamine
    • Cyclophosphamide
    • Ifosfamide
  • Aziridines
    • Thiotepa
    • Mitomycin C
  • Nitrsoureas
    • Carmustine
    • Lomustine
    • Streptozotocin
  • Alkyl alkane sulfonates
    • Busulfan
• Nonclassical alkylating agent
  • Procarbazine
  • Temozolomide
  • Hexamethyl melamine
  • Dacarbazine

II. Platinum compounds: Rosenberg and his co-workers studied anticancer compounds by inhibiting the growth of cancer cells by passing current through electrodes made of platinum. They are classified in to the following types based on platinum analogues.

• Cisplatin
• Carboplatin
• Oxaliplatin

Antitumor antibiotics: Antibiotic compounds are derived from Streptomyces species. Many antibiotics interact with DNA because of cytotoxic profile. The polymorphic structure cleaves the DNA. The following are developed antitumor antibiotics.

• Anthracycline
  • Doxorubicin
  • Epirubicin
  • Daunorubicin
  • Idarubcin
• Anthracenediones
  • Mitoxantrone
  • Bleomycin
  • Dactinomycin

III. Antimetabolites: Compounds which are similar to native compounds and acts as typical nucleotide bases are Antimetabolites. This disrupts the DNA especially during S phase of cell cycle. They are mutagenic but are cytotoxic in nature. Instance for antimetabolite drugs are as follows.

• Folate antimetabolite: Methotrexate
• Pyrimidine antimetabolite: 5 fluorouracil, capecitabine, cytosine arabinoside, gemcitabine
• Purine antimetabolite: 6 mercaptopurine, thioguanine, fludarabine, cladribine, pentostatin

IV. Microtubule targeting drugs: During metaphase, microtubules are formed. Hydrolysis of microtubule and depolymerization developed antimicrotubule drugs for cancer.

• Vinca alkaloids
  • Vincristine
  • Vinblastine
  • Vinorelbine
  • Taxanes
  • Paclitaxel
  • Docetaxel

V. Topoisomerase targeting drugs: Topoisomerase I, ubiquitous enzyme found during replication, recombination and transcription of DNA. It is expressed in mitotic and non mitotic cells. Topoisomerase II is expressed only in mammalian cell cycle.

• Topoisomerase I inhibitors
  • Camptothecin
  • Topotecan
  • Irinotecan
• Topoisomerase II inhibitors
  • Etoposide
  • Teniposide