Pancreatic neuroendocrine tumors (PNETs) are a rare cancer originating from hormone-producing cells within the pancreas. Recent advancements in treatment offer new possibilities and improved outcomes for individuals diagnosed with this condition. The evolution in therapeutic options has transformed PNET management, providing more tailored and effective strategies.
Targeted Therapies
Targeted therapies interfere with molecules involved in cancer cell growth and spread, inhibiting proliferation while minimizing harm to healthy tissues. Everolimus, an oral medication, inhibits the mammalian target of rapamycin (mTOR) pathway. This pathway plays a significant role in cell growth and survival, and its inhibition helps slow tumor progression in advanced PNETs.
Another agent is sunitinib, a multi-targeted receptor tyrosine kinase (RTK) inhibitor. Sunitinib blocks RTKs involved in tumor cell proliferation and angiogenesis, impeding tumor growth and reducing blood supply. Both everolimus and sunitinib are considered for patients with advanced or metastatic PNETs that are progressing. Common side effects include fatigue, diarrhea, and mouth sores.
Peptide Receptor Radionuclide Therapy
Peptide Receptor Radionuclide Therapy (PRRT) is a specialized internal radiation treatment that delivers high doses of radiation directly to neuroendocrine tumor cells. It uses a radioactive substance (radionuclide) linked to a peptide that binds to somatostatin receptors, often highly expressed on tumor cells. Lutathera (Lutetium Lu 177 dotatate) is the most recognized PRRT agent.
Administered intravenously, Lutathera’s dotatate component attaches to somatostatin receptors on PNET cells. Lutetium-177 then emits beta radiation, traveling a short distance to damage tumor cell DNA. This localized radiation minimizes healthy tissue exposure, making it a targeted treatment for somatostatin receptor-positive PNETs. Clinical trials show Lutathera improves progression-free and overall survival in advanced PNETs. Side effects can include temporary bone marrow suppression and kidney function changes.
Immunotherapy and Emerging Treatments
Immunotherapy aims to enhance the body’s immune system to recognize and destroy cancer cells. While successful in other cancers, its role in pancreatic neuroendocrine tumors is still being explored. Research continues to investigate its full potential in PNETs, often focusing on specific patient subgroups.
Immune checkpoint inhibitors, like those targeting the PD-1/PD-L1 pathway, “release the brakes” on immune cells, allowing them to attack cancer. Though single-agent checkpoint inhibitors have limited effectiveness in PNETs, clinical trials explore their use in combination or in responsive patient subgroups. Other investigational treatments include novel small molecules, targeted agents, and combination strategies. Access to these therapies is primarily through clinical trials, which advance treatment knowledge.
Tailoring Treatment to the Individual
Selecting PNET treatment involves a comprehensive, individualized approach. A multidisciplinary team, including medical oncologists, surgeons, radiologists, and pathologists, collaborates to develop a personalized plan. Decisions are based on factors specific to each patient and their tumor.
Key considerations include tumor characteristics like grade, stage, and proliferation index. Somatostatin receptor presence and density on tumor cells determine PRRT eligibility. Patient-specific factors, including overall health, comorbidities, and previous treatments, are important. Treatment goals—controlling symptoms, shrinking the tumor, or slowing progression—guide the therapeutic path.
References
1. National Cancer Institute. Targeted Therapy for Cancer. [Online]. Available: https://www.cancer.gov/about-cancer/treatment/types/targeted-therapy. [Accessed: 25 July 2025].
2. Lutathera (lutetium Lu 177 dotatate) prescribing information. Saint-Genis-Pouilly, France: Advanced Accelerator Applications; 2024. [Accessed: 25 July 2025].
3. American Cancer Society. Immunotherapy for Pancreatic Neuroendocrine Tumors. [Online]. Available: https://www.cancer.org/cancer/types/pancreatic-neuroendocrine-tumor/treating/immunotherapy.html. [Accessed: 25 July 2025].
4. National Comprehensive Cancer Network (NCCN). NCCN Guidelines® for Neuroendocrine Tumors, Version 1.2025. [Online]. Available: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1432. [Accessed: 25 July 2025].