Anti-neoplastic drugs

Anticancer drugs: Anticancer drugs can be divided into classes based on similar mechanisms of action.

Alkylating agents: Alkylating agents act directly on DNA. They cause DNA strand cross-linking, abnormal base pairing, or DNA strand breaks, which prevents the cell from dividing. Alkylating agents are generally considered cell cycle phase nonspecific, meaning they can kill cells in multiple phases of the cell cycle. They’re effective for treating slow-growing cancers.

They include chlorambucil, cyclophosphamide, thiotepa, ifosfamide, nitrosoureas (carmustine), melphalan, and busulfan.

Platinum-containing alkylating agents include cisplatin, carboplatin, and oxaliplatin. In addition to DNA damage, platinum-containing agents also disrupt cell membrane transport and suppress mitochondrial function.
Antimetabolites: Antimetabolites replace natural substances used as building blocks for DNA, which disrupts metabolism and protein synthesis. Antimetabolites are cell cycle specific and are most effective during the S phase, when cells are synthesizing new DNA. Toxicities are most apparent in tissues with rapidly dividing cells (for example, the GI tract and bone marrow).

Examples of antimetabolites include purine and pyrimidine antagonists such as 5FU (fluorouracil) and cytosine arabinoside, and folate antagonists such as methotrexate. Hypomethylating agents such as 5-azacytidine and decitabine act as antimetabolites by affecting cytokine signalling.

Methotrexate inhibits dihydrofolate reductase, which decreases the synthesis of thymidylate and purines. This inhibits DNA synthesis and protein metabolism.

Purine antimetabolite mercaptopurine is a prodrug activated by HGPRT (hypoxanthine guanine phosphoribosyltransferase) into toxic nucleotides. It’s inactivated by xanthine oxidase. If a xanthine oxidase inhibitor such as allopurinol is used concomitantly, the dose of mercaptopurine must be lowered.

5 FU inhibits thymidylate synthase.
Plant alkaloids and antitumor agents: These plant-derived drugs block cell division by binding to microtubule proteins. They are most effective during the S and M phases of the cell cycle. They include vinca alkaloids (derived from the periwinkle plant) such as vincristine and vinblastine; taxanes such as paclitaxel and docetaxel; podophyllotoxins such as etoposide and teniposide; and camptothecans such as irinotecan and topotecan. Podophyllotoxins and camptothecins are also called topoisomerase inhibitors.

Topotecan and irinotecan inhibit topoisomerase I.

Etoposide and teniposide inhibit topoisomerase II.
Antitumor antibiotics (anthracyclines): These drugs bind DNA by intercalating between base pairs, which prevents RNA synthesis. They also cause uncoiling of DNA strands. Examples include doxorubicin, daunorubicin, mitoxantrone, and bleomycin.
Miscellaneous: This is a mixed group and includes drugs such as imatinib, trastuzumab, and tamoxifen.

Anticancer drugs: Anticancer drugs can be divided into classes based on similar mechanisms of action.

Alkylating agents: Alkylating agents act directly on DNA. They cause DNA strand cross-linking, abnormal base pairing, or DNA strand breaks, which prevents the cell from dividing. Alkylating agents are generally considered cell cycle phase nonspecific, meaning they can kill cells in multiple phases of the cell cycle. They’re effective for treating slow-growing cancers.

They include chlorambucil, cyclophosphamide, thiotepa, ifosfamide, nitrosoureas (carmustine), melphalan, and busulfan.

Platinum-containing alkylating agents include cisplatin, carboplatin, and oxaliplatin. In addition to DNA damage, platinum-containing agents also disrupt cell membrane transport and suppress mitochondrial function.
Antimetabolites: Antimetabolites replace natural substances used as building blocks for DNA, which disrupts metabolism and protein synthesis. Antimetabolites are cell cycle specific and are most effective during the S phase, when cells are synthesizing new DNA. Toxicities are most apparent in tissues with rapidly dividing cells (for example, the GI tract and bone marrow).

Examples of antimetabolites include purine and pyrimidine antagonists such as 5FU (fluorouracil) and cytosine arabinoside, and folate antagonists such as methotrexate. Hypomethylating agents such as 5-azacytidine and decitabine act as antimetabolites by affecting cytokine signalling.

Methotrexate inhibits dihydrofolate reductase, which decreases the synthesis of thymidylate and purines. This inhibits DNA synthesis and protein metabolism.

Purine antimetabolite mercaptopurine is a prodrug activated by HGPRT (hypoxanthine guanine phosphoribosyltransferase) into toxic nucleotides. It’s inactivated by xanthine oxidase. If a xanthine oxidase inhibitor such as allopurinol is used concomitantly, the dose of mercaptopurine must be lowered.

5 FU inhibits thymidylate synthase.
Plant alkaloids and antitumor agents: These plant-derived drugs block cell division by binding to microtubule proteins. They are most effective during the S and M phases of the cell cycle. They include vinca alkaloids (derived from the periwinkle plant) such as vincristine and vinblastine; taxanes such as paclitaxel and docetaxel; podophyllotoxins such as etoposide and teniposide; and camptothecans such as irinotecan and topotecan. Podophyllotoxins and camptothecins are also called topoisomerase inhibitors.

Topotecan and irinotecan inhibit topoisomerase I.

Etoposide and teniposide inhibit topoisomerase II.
Antitumor antibiotics (anthracyclines): These drugs bind DNA by intercalating between base pairs, which prevents RNA synthesis. They also cause uncoiling of DNA strands. Examples include doxorubicin, daunorubicin, mitoxantrone, and bleomycin.
Miscellaneous: This is a mixed group and includes drugs such as imatinib, trastuzumab, and tamoxifen.