# An Update on Novel Pharmacotherapies for the Treatment of Neuroendocrine Tumors

**Authors:** Khalil Choucair, Roupen Odabashian, Sushmita Nanja Reddy, Asfar Sohail Azmi, Muhammad Wasif Saif

PMC · DOI: 10.3390/ijms262211095 · International Journal of Molecular Sciences · 2025-11-16

## TL;DR

This paper reviews new treatments for neuroendocrine tumors and highlights the need for better biomarkers and treatment strategies.

## Contribution

The paper proposes a stepwise management approach and emphasizes the potential role of artificial intelligence in future pharmacotherapy.

## Key findings

- Current therapies include somatostatin analogs, tyrosine kinase inhibitors, and mTOR inhibitors.
- Biomarkers may improve diagnosis and post-treatment monitoring for GEP-NETs.
- Optimal therapy timing and sequencing remain unresolved clinical questions.

## Abstract

Neuroendocrine tumors (NETs) are heterogeneous neoplasms with different molecular characteristics and prognosis. Although slow-growing, NETs are often diagnosed at an advanced stage. The treatment choice depends on primary site, extent, grade, growth rate, somatostatin receptor status, functional status, performance status, and comorbidities. Precise knowledge of the biological and molecular features of NETs has led to the development of novel therapies. Therapeutic options include somatostatin analogs, multi-targeted tyrosine kinase inhibitors (e.g., sunitinib), or mammalian targets of rapamycin (mTOR) inhibitors (e.g., everolimus), telotristat ethyl, chemotherapy, and peptide-receptor radionuclide therapy. Pivotal studies that led to approval, treatment-related adverse events, and safety concerns, as demonstrated in clinical trials and real-world clinical practice. Questions, such as the optimal timing, selection, and sequence of therapies, and biomarkers that predict response to the novel agents in an individual patient, remain to be answered. We propose a stepwise approach for the management of advanced Gastro-entero-pancreatic (GEP)-NETs that utilizes a multidisciplinary team of experts. Biomarkers may assist in both the diagnosis and post-treatment follow-up in patients with GEP-NETs. The next decade of research on GEP-NETs is promising and should provide new insights into the molecular underpinnings of this disease, therapy selection, and the sequencing of the available therapies, along with the potential role of AL in NET pharmacotherapy.

## Linked entities

- **Chemicals:** sunitinib (PubChem CID 5329102), everolimus (PubChem CID 6442177), telotristat ethyl (PubChem CID 25181577)

## Full-text entities

- **Genes:** SST (somatostatin) [NCBI Gene 6750] {aka SMST, SST1}, TXK (TXK tyrosine kinase) [NCBI Gene 7294] {aka BTKL, PSCTK5, PTK4, RLK, TKL}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}
- **Diseases:** GEP-NETs (MESH:D018358), neoplasms (MESH:D009369)
- **Chemicals:** telotristat (MESH:C000592493), AL (MESH:D000535), sunitinib (MESH:D000077210), everolimus (MESH:D000068338)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12652171/full.md

## References

148 references — full list in the complete paper: https://tomesphere.com/paper/PMC12652171/full.md

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Source: https://tomesphere.com/paper/PMC12652171