Download to read offline
![4. Anticancer hormones & antagonists [Autosaved].pptx](https://cdn.slidesharecdn.com/ss_thumbnails/4-230509114908-c7824bc8-thumbnail.jpg?width=640&height=640&fit=bounds)
Hormones used in Cancer Management .pptx
- 1.
- 2. Hormone Therapy Use ofagents to slow or stop the growth of hormone sensitive tumours by blocking production of hormones or interfering with their effect on cancer cells
- 4. Hormone responsive cancers/symptoms Cancers/Symptoms •Cancers • Breast • Prostate • Endometrium • Symptoms • Paraneoplastic syndromes • Anorexia Hormones • Estrogen • Progesterone • Testosterone
- 6. Estrogen • Exists inthree forms • Estrone • Post menopausal • Estradiol • Premenopausal • Estriol • Pregnancy
- 8. Gruber CJ etal. N Engl J Med 2002;346:340-352. Classic Pathway of Estrogen Signal Transduction. Estrogen Action • Modulates cell growth by • Increasing stimulatory growth factors eg TGFα • Decreasing Inhibitory growth factors eg TGFβ • Growth factors initiate or prevent progression through cell cycle.
- 14. Estrogen Receptor Expression •Increases with increasing age at diagnosis • Lower expression in Africans • About 40% • Higher expression amongst Caucasians • About 60-70% • Expression determined by staining • Intensity • Proportion that stain positive
- 16. Selective Estrogen Receptor Modulators(SERM):TAMOXIFEN •Used for prevention of premenopausal breast cancer in selected individuals • Treatment of ductal carcinoma in situ • Adjuvant therapy for receptor positive breast cancer • Reduces annual rate of recurrence of breast cancer by 41% and 34% reduction in annual death rate. • Has agonist and antagonist effects in different tissues • Blocks effects of estrogen in breast • Has high therapeutic index
- 17. TAMOXIFEN • Used asadjuvant therapy in both premenopausal and post menopausal women with Estrogen Receptor positive breast cancer • Taken Per Os at 20 mg daily once a day • Recommended duration of intake is 5 years in adjuvant setting • May be taken for 10 years with additional benefit • Used in ER positive metastatic disease • Ineffective in ER negative breast cancer • Agonist effect responsible for endometrial hyperplasia and cancer in post menopausal women
- 18. TAMOXIFEN • Agonist effectresponsible for reduction in Osteoporosis in post menopausal women • Associated with increase in thromboembolic phenomenon • Hot flashes • Associated with vaginal bleeding, dryness/ increased secretions • Retinal toxicity, and cataract reported • Reduces risk of coronary heart disease • Other agents similar to Tamoxifen • Toremifen • Raloxifen
- 19. Fulvestrant • Pure agonist •Competitively binds to ER • Used in the treatment of Estrogen receptor positive metastatic breast cancer • Standard dose 500mg per month by intramuscular injection
- 20.
- 21. AI • They competewith the endogenous substrate androstenedione and testosterone for the active site of the enzyme aromatase • Steroidal molecules bind irreversibly to enzyme • Non- steroidal molecules have a reversible binding, concentration must therefore be maintained. • Reduces the incidence of breast cancer in individuals at risk • Reduces incidence of recurrence and improves survival in ER+ve breast cancer • Only used in menopausal women
- 22. AI • Increased fracturescompared to tamoxifen • Minimum thromboembolic phenomenon • Causes arthralgia and myalgia • Can be combined with LHRH agonist after inducing menopause in premenopausal women • Superior response rates compared to tamoxifen in metastatic setting • Does not have effects on steroidogenesis in the adrenal glands
- 26. LHRH AGONIST • Goserelin •Leuprorelin • Used for medical castration in the palliative management of prostate cancer • May be used to suppress estrogen production to allow use of aromatase inhibitors • Causes an initial flare, induces castrate levels of testosterone in 3-4 weeks • Given as subcutaneous injections monthly, three monthly, every six months and yearly
- 27. LHRH Agonist • Gynaecomastia, •Hot flashes • Osteoporosis • Sweating • Metabolic syndrome •LHRH Antagonist • Degarelix • Doe not cause a flare
- 30. Antiandrogens • Flutamide • Hepatoxicityrare but can be fatal • Bicalutamide • More effective than flutamide • Enzalutamide • Greater receptor affinity • Abiraterone • Hypokalaemia • Hypertension • Fluid overload • Coadministration of steroids important
- 31. Miscelaneous Diethylstilboes triol •For metatastatic breastcancer •And Castrate recurrent prostrate cancer •Associated with thromboembolic phenomenon Medroxyprogestero ne and Megestrol •Previously used for advanced breast cancer and metastatic endometrial cancer •Anorexia and cachexia •Causes adrenal suppression
- 32. Octreotide • Somatostatin analogue •Used in the treatment of carcinoid syndrome; diarrhoea and flushing • And other hormonal excess syndromes associated with pancreatic islet cell cancers and acromegaly
Editor's Notes
- #8 Figure 3. Classic Pathway of Estrogen Signal Transduction. When an estrogen molecule binds to an estrogen receptor (ER), the receptor dissociates from its cytoplasmic chaperones, the receptor-associated proteins. The hormone–receptor complex then moves to the nucleus, where it binds to DNA and initiates transcription. Transcription is catalyzed by RNA polymerase II (POL II) and requires the assembly of various proteins, including the TATA-box–binding protein (TBP) and other associated factors at a TATA box. Other transcription factors join thereafter, completing the preinitiation complex. Activated, phosphorylated (P) estrogen receptors interact with several proteins, such as the 160-kD steroid-receptor coactivator protein (P160) and p300–cyclic AMP response-element–binding protein (CBP). This complex binds to the estrogen-response element (ERE) through the DNA-binding domain (DBD) of the receptor and stimulates transcription; proposed mechanisms of stimulation include stabilization of the preinitiation complex, chromatin remodeling, and interaction with other transcription factors.