Lecture 8 Flashcards
Prostate Cancer
What is the primary function of the prostate gland?
A: To produce seminal fluid and control urine flow.
What role do androgens play in the prostate?
A: Androgens (like testosterone) regulate the growth, differentiation, and function of the prostate.
What is the major source of testosterone in the male body?
A: The testes, producing 90-95% of circulating testosterone.
What hormone from the hypothalamus stimulates the production of testosterone?
A: Luteinizing Hormone-Releasing Hormone (LHRH).
What is the role of the CYP17 enzyme in androgen production?
A: CYP17 is critical for converting pregnenolone/progesterone into androgens or cortisol in the biosynthesis pathway.
What happens to Prostate-Specific Antigen (PSA) levels when androgens stimulate prostate cancer growth?
A: PSA levels increase as a result
Q: What effect does Dihydrotestosterone (DHT) have on prostate cells?
A: DHT binds to androgen receptors, signaling prostate cell growth and proliferation while preventing apoptosis.
How does prostate cancer depend on androgens for growth?
A: Androgens, particularly testosterone, are converted to Dihydrotestosterone (DHT), which binds to androgen receptors in prostate cancer cells to promote cell growth and prevent apoptosis.
When should PSA screening be stopped in men?
A: Screening should be considered for discontinuation at age 70 or when life expectancy is less than 10 years, or if PSA levels remain <1 ng/mL at age 60.
In which populations is prostate cancer screening more likely to be considered?
A: Screening is more likely in men with higher risk, such as those of African ancestry or with a family history of prostate cancer before age 65.
Q: At what age should men begin discussing prostate cancer screening with their healthcare provider?
A: Men should begin discussing screening at age 50, or age 45 if they are at higher risk (e.g., family history, African ancestry).
Why is bone health important in prostate cancer patients receiving Androgen Deprivation Therapy (ADT)?
A: ADT increases the risk of osteoporosis and fractures due to reduced testosterone levels, which decrease bone mineral density.
What is the primary treatment for metastatic castration-sensitive prostate cancer (mCSPC)?
A: The backbone treatment is Androgen Deprivation Therapy (ADT), often combined with Abiraterone + prednisone, docetaxel,( if pt is feeling well) or novel antiandrogens like enzalutamide or apalutamide.
How is metastatic castration-resistant prostate cancer (mCRPC) treated?
A: Treatment includes Abiraterone + prednisone, enzalutamide, or chemotherapy (docetaxel, cabazitaxel) for those who progress despite ADT.
What is the difference between castrate-sensitive and castrate-resistant prostate cancer?
A: Castrate-sensitive cancer responds to testosterone deprivation via ADT, while castrate-resistant cancer continues to progress despite low testosterone levels.
Q: What therapies are available for non-metastatic castrate-resistant prostate cancer (nmCRPC)?
A: Novel antiandrogens like enzalutamide, apalutamide, or darolutamide are used in combination with ADT.
Q: What are the two main types of ADT in prostate cancer treatment?
A: LHRH agonists (e.g., leuprolide, goserelin) and LHRH antagonists (e.g., degarelix).
Q: What is the mechanism of action of LHRH agonists in prostate cancer?
A: LHRH agonists initially increase luteinizing hormone (LH), causing a testosterone flare, but with chronic administration, they downregulate LHRH receptors, decreasing testosterone production.
Q: What is the benefit of using an LHRH antagonist like degarelix over an LHRH agonist?
A: LHRH antagonists directly reduce testosterone without causing a flare in testosterone levels.
Q: What is the flare response in ADT, and how can it be managed?
A: The flare is a temporary increase in testosterone at the start of LHRH agonist therapy, which can be managed with antiandrogens like bicalutamide for the first month of treatment.
Q: What are the common side effects of ADT?
A: Hot flashes, decreased libido, erectile dysfunction, osteoporosis, fatigue, and metabolic changes (e.g., hyperlipidemia, insulin resistance).
What is the mechanism of action of Abiraterone in prostate cancer treatment?
A: Abiraterone is a CYP17 inhibitor that reduces androgen production in the testes, adrenal glands, and prostate cancer cells.
Why is prednisone administered with Abiraterone?
A: Prednisone compensates for the mineralocorticoid side effects of abiraterone, such as hypertension, hypokalemia, and fluid retention, caused by increased ACTH levels.
Why is darolutamide preferred in patients at risk for CNS side effects?
A: Darolutamide has minimal penetration through the blood-brain barrier, reducing the risk of CNS side effects like seizures.
What is the mechanism of action of enzalutamide, apalutamide, and darolutamide?
A: These novel antiandrogens inhibit androgen receptor signaling by blocking androgen binding, receptor translocation, and DNA binding in prostate cancer cells.
More affinity with LHRH agonist action , inhibits nuclear AR translocation
Which CYP enzyme does Abiraterone strongly inhibit, and what are the clinical implications?
A: Abiraterone strongly inhibits CYP2D6, which can increase the plasma concentrations of drugs metabolized by CYP2D6, such as beta-blockers and antidepressants.
What are the drug interactions associated with enzalutamide and apalutamide?
A: Both are strong inducers of CYP3A4, CYP2C9, and CYP2C19, potentially reducing the effectiveness of drugs metabolized by these enzymes (e.g., warfarin, anticonvulsants).
What precautions should be taken when using darolutamide in patients on other medications?
A: Darolutamide is a weak inducer of CYP3A4 and a substrate of PGP; caution should be used with drugs that affect these pathways, but it has fewer drug interactions compared to enzalutamide and apalutamide.
Which of the new ADT has longer 1/2 lives ?
Enzalutimide
Apalutimide
