Chapter 27 — Quiz

Peptides in Oncology: Hormone-Axis Blockade, Somatostatin Analogs, and Radioligand Therapy

22 questions. Answer all of them before opening the key.

1. Approximately how long have peptide drugs been the standard backbone of androgen deprivation therapy in prostate cancer?

a) Since about 2015 b) Since the mid-1980s c) Since 2005 d) They are not; androgen deprivation uses small molecules

2. A GnRH agonist produces suppression of the axis because:

a) It blocks the GnRH receptor b) It destroys pituitary gonadotroph cells c) Continuous, non-pulsatile receptor stimulation causes desensitization and downregulation d) It is metabolized into an antagonist

3. The "flare" is best described as:

a) An allergic reaction to the peptide b) A contaminant effect from poor manufacturing c) The transient testosterone rise produced by the agonist's own stimulating action, before desensitization takes hold d) An immune response to a foreign protein

4. The flare is clinically managed by:

a) Reducing the depot interval b) Concurrent antiandrogen cover during the surge window c) Switching to a different agonist d) Pretreatment with corticosteroids

5. From the name alone, which of these blocks its receptor rather than stimulating it?

a) Triptorelin b) Sermorelin c) Degarelix d) Tesamorelin

6. Why did GnRH antagonists reach the clinic later than GnRH agonists?

a) The receptor was not identified until the 2000s b) Designing a peptide antagonist was harder than exploiting agonist-induced desensitization, and early candidates had histamine-release problems c) Regulators refused to approve antagonists for cancer d) Antagonists were less effective at suppressing testosterone

7. Relugolix is an oral option for androgen deprivation. Which statement about it is correct?

a) It is a peptide that survives digestion because it is cyclic b) It is a peptide delivered with an absorption-enhancing excipient c) It is a small molecule — a nonpeptide antagonist of the GnRH receptor d) It is a prodrug that becomes a peptide after absorption

8. Octreotide is:

a) An 8-residue cyclic analog of somatostatin containing D-amino acids b) A 14-residue linear copy of native somatostatin c) A monoclonal antibody against the somatostatin receptor d) A 28-residue recombinant protein

9. Which of these is not one of the stabilization strategies used in octreotide?

a) Cyclization via a disulfide bond b) D-amino acid substitution c) Truncation to the active core d) PEGylation of the N-terminus

10. Somatostatin analogs are used in acromegaly because:

a) They stimulate growth hormone release b) They supply, pharmacologically, the axis's own inhibitory brake on GH secretion c) They shrink the pituitary gland directly d) They block the growth hormone receptor in peripheral tissue

11. The claims "somatostatin analogs control carcinoid symptoms" and "somatostatin analogs delay tumor progression" require separate ratings because:

a) They apply to different molecules b) One is supported and the other is not c) They involve different populations and endpoints and were established separately by different trials d) One is an approved indication and the other is illegal to state

12. PROMID and CLARINET are:

a) Two randomized placebo-controlled trials supporting an antiproliferative effect of somatostatin analogs b) Two PRRT trials c) Two prostate cancer trials of GnRH antagonists d) Two observational registries of neuroendocrine tumor patients

13. In peptide receptor radionuclide therapy, the therapeutic agent is:

a) The peptide b) The chelator c) The radionuclide d) The linker

14. The peptide's role in PRRT is best summarized as:

a) A receptor agonist producing an antitumor signal b) A delivery address that determines where the payload ends up c) An immunomodulator d) A protease inhibitor protecting the payload

15. Lutetium-177 is useful in therapy partly because, alongside its therapeutic emissions, it:

a) Has a half-life of several years b) Emits gamma photons that can be imaged, allowing post-treatment verification of delivery c) Crosses the blood-brain barrier d) Is orally bioavailable

16. NETTER-1 enrolled patients with tumors that were:

a) Any grade, any primary site, treatment-naive b) Midgut, well-differentiated, somatostatin-receptor-positive, and progressive on octreotide c) Pancreatic and high-grade d) Selected only by symptom burden

17. NETTER-1's primary endpoint was:

a) Overall survival b) Quality of life c) Progression-free survival d) Objective response rate

18. "Theranostic" refers to:

a) A drug that treats two diseases b) A targeting system that can carry either a diagnostic or a therapeutic radionuclide, allowing the target to be imaged before treatment c) A combination of chemotherapy and radiotherapy d) A companion blood test

19. Which statement about PSMA-targeting ligands is accurate?

a) They are all peptides b) Most clinically important PSMA ligands are small molecules or peptidomimetics, not peptides c) They are monoclonal antibodies d) They are somatostatin analogs

20. Compared with an antibody-drug conjugate, a peptide-drug conjugate typically has:

a) Better tissue penetration, shorter half-life, cheaper manufacture, lower payload capacity b) Worse tissue penetration and longer half-life c) Identical properties at lower cost d) Higher payload capacity and longer half-life

21. According to §27.8, every successful oncology peptide does one of three things. Which is not one of them?

a) Shuts down a hormone axis b) Replaces or mimics an inhibitory hormone c) Delivers something to an address d) Broadly supports and optimizes healthy cellular function

22. Why does the chapter argue that oncology is the field where this pattern is most visible?

a) Oncologists are unusually skeptical of peptides b) Oncology has hard, scheduled endpoints and little tolerance for unfalsifiable claims c) Oncology drugs are cheaper to test d) Oncology approvals are easier to obtain

Answer key **1. (b)** Since the mid-1980s. Leuprolide and its relatives have been the dominant route to androgen deprivation for about four decades — one of the chapter's central and most surprising facts. **2. (c)** Continuous, non-pulsatile stimulation desensitizes and downregulates the receptor. This is Chapter 3 §3.5's pulsatility principle applied deliberately: a stimulator becomes a suppressor because the axis reads pattern, not presence. **3. (c)** The flare is the agonist's own stimulating action observed before desensitization takes hold. It is not an allergic, immune, or contaminant effect — it is the intended mechanism in its first phase, which is why the chapter treats it as the best teaching moment available. **4. (b)** Concurrent antiandrogen cover. An androgen receptor blocker is started before or alongside the agonist so that a transient testosterone rise cannot reach the receptor that matters. **5. (c)** Degarelix. `-relix` = antagonist; `-relin` = agonist. Triptorelin, sermorelin, and tesamorelin all carry the agonist stem. **6. (b)** Antagonist design was the harder chemistry problem, and early candidates ran into histamine-release reactions. Abarelix reached US approval in 2003 and was withdrawn within a couple of years. The general lesson: the order in which drug classes appear reflects tractability at least as much as merit. **7. (c)** Relugolix is a small molecule. That is precisely why it can be swallowed — a direct application of Chapter 1's point that peptides are digested. The oral option is oral because it stopped being a peptide. **8. (a)** An 8-residue cyclic analog containing D-amino acids. Shorter than native somatostatin, and far more stable. **9. (d)** PEGylation is a real half-life-extension strategy (Chapter 33) but is not among the three used in octreotide, which are truncation, cyclization, and D-amino acid substitution — plus a C-terminal alcohol modification. **10. (b)** They supply the axis's own brake pharmacologically. This is the direct link back to Chapter 14, and a reminder that the same molecule can be an endocrinology drug and an oncology drug because a pituitary adenoma is a tumor. **11. (c)** Different populations, different endpoints, established separately. This is Rule 6 of the rating system — one molecule, many ratings — in its cleanest form. A single rating for "octreotide" would compress away exactly the information you need. **12. (a)** Two randomized placebo-controlled trials supporting the antiproliferative claim: PROMID (octreotide LAR, midgut) and CLARINET (lanreotide, enteropancreatic). **13. (c)** The radionuclide. The peptide is not the drug. **14. (b)** A delivery address. This is the chapter's most striking inversion of what the rest of the book trains you to look for. **15. (b)** Its imageable gamma emissions allow post-treatment verification of where the therapy went — which becomes the basis of the theranostic loop in §27.6. **16. (b)** Midgut, well-differentiated, somatostatin-receptor-positive, progressive on octreotide. Every clause is load-bearing, and dropping them is the most common way an accurate oncology finding becomes an inaccurate public claim. **17. (c)** Progression-free survival. Note that longer follow-up did not demonstrate a statistically significant overall survival benefit — so "helps patients live longer" goes beyond the trial. **18. (b)** A targeting system usable for both imaging and therapy by exchanging the radionuclide. Its clinical value is that you can confirm the target is present in the individual patient before treating. **19. (b)** Most clinically important PSMA ligands are small molecules or peptidomimetics. The chapter insists on this precision: PRRT is the peptide case, PSMA radioligand therapy is the same idea executed with a nonpeptide ligand. **20. (a)** Better penetration, shorter half-life, cheaper manufacture, lower payload capacity. Read that as a genuine trade, not an upgrade. **21. (d)** There is no fourth box. No approved oncology peptide has the job of broadly supporting or optimizing a healthy system — because that is not a job, it is a description with no endpoint attached. **22. (b)** Hard endpoints arriving on schedule. Patients progress or they do not; they are alive at the data cutoff or they are not. A field with endpoints like that develops an immune system against unfalsifiable claims.