Anticancer Med Chem 2 Flashcards
What are the hormonal agents in cancer therapy?
- Antiestrogens
- Aromatase Inhibitors
- Antiandrogens
- LHRH (GnRH) Analogues and Antagonist
What are the antiestrogens cancer drugs?
- Tamoxifen Citrate
- Raloxifene
- Megestrol Acetate
- Fluvestrant
What are the aromatase Inhibitors?
- Anastrazole
- Letrozole
- Exemestane
What are the antiandrogen cancer therapy
- Flutamide
- Nilutamide
- Bicalutamide
- Enzalutamide
What are the LHRH (GnRH) Analogues and Antagonst?
- Goserelin
- Leuprolide
In which cancers would you use endocrine cancer therapy?
- Breast cancer
- Prostate cancer
- Endometrium cancer
Why would estrogen therapy possibly work for breast cancer?
Breast cancer cells can be Estrogen receptor +. estrogen can drive growth of the cancer.
What is Aromatase?
-a P450 enzyme. It catalyzes the last step of estrogen biosynthesis. It converts androstenedione to estrone (E1) and testosteerone to estraiol (E2)
what do aromatase inhibitors do?
-They block the aromatase, and decrease estrogen levels
What are AIs given to?
Postmeonpausal women who have a ER+ tumor.
MOA of Exemestane?
- Androgen analogue
- IRREVERSIBLY binds to aromatase
- Called Suicide inhibitor.
MOA of Anastrozole or Letrozole?
- Contains functional group that binds to heme ironn to the cytochrome P450, interfering with the hydroxylation rxns.
- Competes REVERRSIBLY for the andgrogen bindign site.
Is SERMs tissue selective?
Yes
How is CYP2D6 related to Tamoxifen?
TAM is dependent on its conversion by the hepatic drug-metabolizing enzyme cytochrome P450 2D6 to its metabolite, endoxifen.
What medications would patients on Tamoxifen need to avoid?
-Avoid CYP2D6 inhibitors, like Fluoxetine, and paroxetine
What is Raloxifene approved for?
- Prevention and treatment of osteoporosis in postmenopausal women
- Chemoprevention of invasive breast cancer in post menopausal women at high risk
What is a Fluvestrant?
-A selective ER down-regulator (SERDs)…(promotes ER degradation, reduces ER rpotein level)
Does Fulvestrant show cross-resistance with Tamoxifen?
No. Bc it is a pure ER antagonist
What is the MOA of Enzalutamide?
- 5-8 fold higher affinity to AR compared to bicalutamide.
- It competes with androgens and binds to AR ligand binding domains to reduce AR nuclear translocation and inhibits the assocation of AR to androgen response elements (ARE)
What does Abiraterone do?
-Blocks androgen biosynthesis.
What is the first line treatment for advanced/metastatin prostate cancer?
-Androgen Deprivation Therapy (ADT)
what is the leading ADT?
LHRH (GnRH) agonists
Function of Protein Kinase?
-catalyze transfer of the terminal phosphate of ATP to proteinn substrates that usually contain a serine (S), Threonine (T), or tyrosine residue (Y)
What are the three major types of kinases?
- Tyrosine Kinases
- Serine /Threonine Kinases
- Tyrosine/Serine/Threonine Kinases