Imatinib Mesylate

UNDER REVIEW (September 2016)

Mechanism of Action:

Imatinib is a 2-phenylaminopyrimidine derivative that functions as a specific inhibitor of a number of tyrosine kinase enzymes. It occupies the TK domain, leading to a decrease in activity. There are a large number of TK enzymes in the body, including the insulin receptor. Imatinib is specific for the TK domain in abl (the Abelson proto-oncogene), c-kit and PDGF-R (platelet-derived growth factor receptor).

Lecture and CAL materials:

  • Lecture: Introduction to the Treatment of Cancer

Cisplatin

UNDER REVIEW (September 2016)

Mechanism of Action:

Cisplatin is a platinum-based alkylating agent used to treat a variety of cancers. Alkylating agents stop tumor growth by cross-linking guanine bases in DNA strands, which makes the strands unable to uncoil and separate. As this prevents DNA replication, the cells can no longer divide.

Lecture and CAL materials:

  • Lecture: Introduction to the Treatment of Cancer

Vincristine

UNDER REVIEW (September 2016)

Mechanism of Action:

All vinca alkaloids work by inhibiting the cell-cycle, halting mitosis of affected cells and causing cell death. The mechanism involves binding to the tubulin monomers and keeping the microtubules (spindle fibers) from forming. Other vinca alkaloids with a similar action include vinblastine, vindesine and vinorelbine. Other drugs that inhibit spindle formation during cell division are paclitaxel (Taxol) and docetaxel (Taxotere).

Lecture and CAL materials:

  • Lecture: Introduction to the Treatment of Cancer

Fluorouracil

UNDER REVIEW (September 2016)

Mechanism of Action:

An example of the group of anticancer drugs known as antimetabolites. Others include other pyrimidine antagonists (capecitabine and gemcitabine which are both ‘prodrugs’ that are converted into 5-FU in the body, premetrexed), folate antagonists (methotrexate), and purine antagonists (mercaptopurine, cytarabine, fludarabine).

Lecture and CAL materials:

  • Lecture: Introduction to the Treatment of Cancer

Doxorubicin

UNDER REVIEW (September 2016)

Mechanism of Action:

An example of a group of anticancer drugs known as cytotoxic antibiotics. Other examples include duanorubicin, epirubicin, bleomycin and mitomycin. Doxorubicin is an anthracycline antibiotic that exerts its effects on cancer cells via two different mechanisms: 1. Intercalation: it wedges between the bases of DNA and blocks DNA synthesis and transcription. 2. Enzyme inhibition: it inhibits the activity of an enzyme, topoisomerase type II. This leads to breaks in the genomic DNA. Both of these mechanisms result in DNA disruption that ultimately can lead to the death of the cell.

Lecture and CAL materials:

  • Lecture: Introduction to the Treatment of Cancer

Cyclophosphamide

Mechanism of Action:

The commonest example of an alkylating agent, a group of drugs which have the ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA strands, which makes the strands unable to uncoil and separate. As this prevents DNA replication, the cells can no longer divide. As for all anti-cancer drugs the same mechanism that kills the rapidly dividing malignant cells may also harm high turnover healthy cells of the gut mucosa, hair, bone marrow and reproductive organs.

Lecture and CAL materials:

  • Lecture: Introduction to the Treatment of Cancer

Methotrexate

Mechanism of Action:

Methotrexate is classified as an antimetabolite drug. It blocks DNA synthesis in proliferating cells by binding with and blocking the action of dihydrofolate reductase which enables regeneration of folate, a cofactor in the production of substrates for DNA and RNA synthesis. By this mechanism it prevents cell proliferation making it both immunosuppressant and cytotoxic.

Lecture and CAL materials:

Tamoxifen

Mechanism of Action:

Tamoxifen is an antiestrogen (blocks the effect of estrogen on tissue). Tamoxifen and several of its metabolites (particularly 4- hydroxytamoxifen) bind to nuclear oestrogen receptors in oestrogen-sensitive tissues, and also to a microsomal protein termed the ‘anti-oestrogen binding site’. Tamoxifen interferes with the physiological sequence by which oestrogen binds to its receptor, is translocated in the nucleus and then activates messenger RNA synthesis. Although the tamoxifen-receptor complex is transported in the nucleus in the same way as oestrogen-receptor complex, it fails to activate synthesis of mRNA. Tamoxifen is one of the group of drugs known as selective oestrogen receptor modulators or SERMs (others are clomifene and raloxifene) which inhibit oestrogenic effects in some tissues but augment them in others. Also stimulates FSH release.

Lecture and CAL materials: