What are the medical uses of peptides in treating various conditions, including growth hormone deficiency, diabetes, and cancer?

Medical Uses of Peptides

Diagnostic Applications

Peptides serve as critical biomarkers for diagnosing and monitoring neuroendocrine tumors (NETs), with specific peptide measurements guiding tumor localization and treatment response. 1

• Chromogranin A (CgA) is the primary diagnostic marker for most NETs, elevated in over 80% of gastroenteropancreatic tumors and useful for monitoring metastatic disease 1
• C-peptide and pro-insulin measurements are essential for diagnosing insulinomas, where insulin levels appear inappropriately normal relative to blood glucose during hypoglycemic episodes 1
• Pancreatic polypeptide (PP) serves as a marker for non-functioning pancreatic NETs 1
• Neurokinin A provides prognostic value in serotonin-secreting small bowel tumors 1
• Fasting specimens are required for accurate measurement of insulin, gastrin, and PP, as these peptides remain elevated for over 6 hours postprandially 1

Therapeutic Applications in Neuroendocrine Tumors

Somatostatin Analogues for Symptom Control

Somatostatin analogues (octreotide, lanreotide) are the first-line hormonal treatment for functional NETs, particularly carcinoid syndrome, providing substantial symptom relief in most patients. 2

• Initial dosing: Octreotide 50-100 mcg subcutaneously 2-3 times daily, with maximum doses up to 1500 mcg/day based on clinical response 2, 3
• Long-acting formulations (octreotide LAR, lanreotide) can be administered every 4 weeks, overcoming the short half-life of native somatostatin 4
• Carcinoid syndrome management: Controls diarrhea and flushing in midgut and lung NETs 2
• VIPomas: Effective for profuse watery diarrhea, with lanreotide doses titrated against vasoactive intestinal peptide levels 2, 3
• Acromegaly: Reduces growth hormone and IGF-1 levels in patients with inadequate surgical response 4, 3

Antiproliferative Effects

Octreotide LAR demonstrates disease-stabilizing effects in metastatic midgut NETs, with median time to progression of 14.3 months versus 6 months with placebo, particularly in patients with low hepatic tumor burden and resected primary lesions. 1

• Partial/complete tumor response occurs in fewer than 10% of pancreatic NET patients 1
• Tumor stabilization achieved in 24-57% of patients with documented progression 1

Peptide Receptor Radionuclide Therapy (PRRNT)

Radiolabeled peptides (90Y-DOTATOC, 177Lu-DOTATATE) deliver tumoricidal doses to somatostatin receptor-positive tumors, achieving partial responses in 9-29% and complete remission in 2-6% of gastroenteropancreatic NETs. 1

• 177Lu-DOTATATE is preferred for patients with massive liver metastases due to lower renal toxicity (3.8% creatinine clearance loss per year versus 7.3% with 90Y-DOTATOC) 1
• Dosing: 3-6 GBq administered at 6-8 week intervals to cumulative activity of 12-18 GBq 1
• Patient selection: Requires adequate somatostatin receptor expression on imaging, reasonable bone marrow reserve, and adequate renal function 1
• Renal protection: Amino acid co-administration (particularly D-lysine) is mandatory to minimize nephrotoxicity 1
• High somatostatin receptor tumor expression predicts significantly longer survival 1

Critical Care Applications

In perioperative settings or stress situations (anesthesia, surgery, hepatic artery embolization), patients with carcinoid syndrome require increased octreotide coverage at 50 mcg/hour intravenously to prevent carcinoid crisis. 2

Therapeutic Applications in Diabetes

GLP-1 receptor agonists (exenatide, liraglutide, semaglutide, dulaglutide, tirzepatide) stimulate glucose-dependent insulin secretion while inhibiting glucagon release, with minimal hypoglycemia risk due to their glucose-dependent mechanism. 1

• Mechanism: Activate G-protein coupled GLP-1 receptors on pancreatic β-cells, increasing intracellular calcium and insulin exocytosis 1
• Tirzepatide (dual GIP/GLP-1 receptor agonist) produces greater HbA1c and weight reductions compared to semaglutide and dulaglutide 1
• Cardiovascular benefits: Reduce rates of non-fatal myocardial infarction, stroke, and death in patients with type 2 diabetes and obesity 1
• Gastric emptying delay is the primary determinant of postprandial glycemic response 1

Cancer Treatment Applications

Peptides function as targeted cancer therapeutics through three primary mechanisms: direct cytotoxic activity, carrier molecules for chemotherapy/radioisotopes, and immune system activation via cancer vaccines. 5, 6, 7

• Targeted therapy: Peptides specifically recognize cancer cell receptors without affecting normal cells, reducing systemic toxicity 8, 9
• Drug conjugation: Peptides serve as carriers directing cytotoxic agents to cancer cells with higher receptor expression 8
• Membrane disruption: Bioactive peptides form pores in cancer cell membranes, inducing necrosis or apoptosis 9
• Combination therapy: Peptides combined with conventional chemotherapy or radiation achieve synergistic effects 5
• Advantages: Low molecular weight, high activity, minimal immunogenicity, good biocompatibility, and ease of synthesis modification 9, 7

Important Monitoring and Safety Considerations

Somatostatin Analogue Monitoring

• Monitor circulating hormone levels and urinary hormones during treatment 2
• Perform regular imaging surveillance 2
• Common adverse effects: Gallbladder abnormalities (>10%), sinus bradycardia, diarrhea, hyperglycemia, hypothyroidism 3
• Cardiac monitoring: Consider in patients receiving intravenous octreotide due to increased risk of atrioventricular blocks 3
• Glucose metabolism: Both hypoglycemia and hyperglycemia may occur; adjust anti-diabetic medications accordingly 3

PRRNT Toxicity Management

• Renal toxicity: Kidneys are dose-limiting organs; patients with hypertension or diabetes have increased risk 1
• Bone marrow toxicity: Grade 3-4 toxicity in <10-13% of 90Y-DOTATOC cycles and 2-3% of 177Lu-DOTATATE cycles 1
• Fertility considerations: Male patients should consider sperm banking; avoid pregnancy for 6 months post-treatment 1
• Reduce administered activity in patients with massive liver metastases and impaired hepatic function 1

Drug Interactions

Octreotide requires monitoring and dose adjustment when used with cyclosporine, insulin, oral hypoglycemic agents, beta-blockers, and bromocriptine. 3

• Discontinue octreotide at least 24 hours prior to lutetium Lu 177 dotatate administration 3
• Withdraw short-acting somatostatin analogues 24-48 hours before diagnostic imaging with 68Ga-peptides 1