The emerging role of targeted therapies for advanced well-differentiated gastroenteropancreatic neuroendocrine tumors

ABSTRACT

Introduction: Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are unique and complex neoplasms, exhibiting a wide spectrum of diverse clinical behaviors. The contemporary management of well-differentiated GEP-NETs is marked by the availability of a wide range of targeted therapies.

Areas Covered: For patients with localized or oligometastatic disease, surgical resection remains the preferred approach and is associated with excellent long-term outcomes. For patients with unresectable but isolated liver metastases, multiple liver-directed therapies, including hepatic arterial based therapies and ablative techniques, exist. For patients with metastatic and progressive disease, a number of systemic therapies exist: molecular targeted agents, peptide receptor radionuclide therapy (PRRT), and systemic chemotherapy. Furthermore, somatostatin analogs (SSA) are an important component of therapy, both effectively controlling symptoms of hormonal overproduction and contributing to slowing tumor progression.

Expert Opinion: In the near future, advances in our understanding of tumor biology, genetics, immunology, nanotechnology, and radiation pharmacology should only continue to expand the availability of targeted therapies, improving the outcomes of patients with GEP-NETs. We herein review the management of advanced well-differentiated GEP-NETS with a particular emphasis on the role of targeted therapies.

KEYWORDS:

• Neuroendocrine
• gastroenteropancreatic
• PRRT
• targeted agents
• therapy
• treatment

Article Highlights

• Well-differentiated GEP-NETs are a unique and complex neoplasm, exhibiting a wide spectrum of diverse clinical behaviors.

• For patients with localized or oligometastatic disease, surgical resection remains the preferred approach and is associated with excellent long-term outcomes. For patients with unresectable but isolated liver metastases, multiple liver-directed therapies, including hepatic arterial based therapies and ablative techniques, exist.

• For patients with metastatic and progressive disease, a number of systemic therapies exist: molecular targeted agents, traditional systemic chemotherapy, and increasingly PRRT.

• SSAs are an important component of therapy, both effectively controlling symptoms of hormonal overproduction and contributing to slowing tumor progression.

• In the near future, advances in our understanding of tumor biology, genetics, immunology, nanotechnology, and radiation pharmacology should only continue to expand the availability of targeted therapies, improving the outcomes of patients with GEP-NETs.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.