Question

Look up the following cancer drugs/therapyand explain how each works. In your answer include mechanism of action, drug/therapytarget (specific protein), and specific pathway targeted. Explain why this is an anti-cancer drug/therapy(what is it doing to the cancer cells?) Be sure to include references used

.a.ABT-737

b.ONYX-015

c.vinblastine

d.cyclapolin

e.TNP-470

Answer 1

ABT-737

ABT-737 is a BH3 mimetic that binds to and inhibits BCL-2, BCL-xL and BCL-w with high affinity but has a lower binding to MCL1 23. Consistent with its mechanism of action, the ability of ABT-737 to kill cells is dependent on the presence of BAK or BAX in the cell.

ABT-737 is a small-molecule BH3 mimetic that exhibits single-agent activity against lymphoma and small-cell lung cancer in preclinical studies. We here report that ABT-737 effectively kills acute myeloid leukemia blast, progenitor, and stem cells without affecting normal hematopoietic cells. ABT-737 induced the disruption of the BCL-2/BAX complex and BAK-dependent but BIM-independent activation of the intrinsic apoptotic pathway. In cells with phosphorylated BCL-2 or increased MCL-1, ABT-737 was inactive. Inhibition of BCL-2 phosphorylation and reduction of MCL-1 expression restored sensitivity to ABT-737. These data suggest that ABT-737 could be a highly effective antileukemia agent when the mechanisms of resistance identified here are considered.

ONYX-015

An E1B-55kDa-deleted adenovirus that is able to selectively replicate in and lyse TP53-deficient human tumor cells. After tumor cell lysis, released viruses infect neighboring tumor cells, tripping a chain of ONYX-015-mediated tumor cell cytotoxicity. Check for active clinical trials using this agent. (NCI Thesaurus).

Patents for the therapeutic use of ONYX-015 are held by ONYX Pharmaceuticals and it was used in combination with the standard chemotherapeutic agents cisplatin and 5-fluorouracil to combat head and neck tumours.Onyx-015 has been extensively tested in clinical trials, with the data indicating that it is safe and selective for cancer. However, limited therapeutic effect has been demonstrated following injection and systemic spread of the virus was not detected. ONYX-015 when combined with chemotherapy, however, proved reasonably effective in a proportion of cases. During these trials a plethora of reports emerged challenging the underlying p53-selectivity, with some reports showing that in some cancers with a wild-type p53 ONYX-015 actually did better than in their mutant p53 counterparts. These reports slowed the advancement through Phase III trials in the US, however recently China licensed ONYX-015 for therapeutic use as H101.Further development of Onyx-015 was abandoned in the early 2000s, the exclusive rights being licensed to the Chinese company, Shanghai Sunway Biotech. On November 17, 2005, the Chinese State Food and Drug Administration approved H101, an oncolytic adenovirus similar to Onyx-015 (E1B-55K/E3B-deleted), for use in combination with chemotherapy for the treatment of late-stage refractory nasopharyngeal cancer.Outside of China, the push to the clinic for ONYX-015 has been largely been discontinued for financial reasons and until a real mechanism can be found.

VINBLASTINE

Vinblastine is a chemical analogue of vincristine, an alkaloid derived from the Madagascar periwinkle plant Vinca rosea (Catharanthus roseus), from which it derives its name.

Vinblastine (VBL), sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small cell lung cancer, bladder cancer, brain cancer, melanoma, and testicular cancer.

Vinblastine is used in combination with other chemotherapy drugs to treat Hodgkin's lymphoma (Hodgkin's disease) and non-Hodgkin's lymphoma (types of cancer that begin in a type of white blood cell that normally fights infection), and cancer of the testicles.