New and emerging somatostatin therapies for neuroendocrine tumors: "what is in the pipeline".
AI interpretation is pending for this paper.
Open original publication →What the AI sees
Not AI summarized yet.
Research significance
Pending deeper interpretation.
Source abstract
INTRODUCTION: Somatostatin receptors (SSTRs) have played a central role in all aspects of the management of neuroendocrine/endocrine neoplasms (NENs). This includes in diagnosis of NENs with the widespread use of radiolabeled SSTR ligands to localize both the primary tumor location and extent of the tumors, as well as confirm its NEN nature. In NEN management non-radiolabeled SSTR agonists are the first line for control of the hormone-excess state for most functional NENs (F-NENs) as well as for the initial cytotoxic treatment of advanced tumor growth, and more recently, the use of radiolabeled SSTR ligands for the treatment of more aggressive advanced disease, as well as the assessment of tumor location, tumor extent and response to therapies. While somatostatin analogs (SSTA) have been successful in all of the above areas, there is increasing need for improvement, because not all patients respond to existing SSTAs therapies, others become resistant with time to existing SSTA treatment, current imaging with radiolabeled SSTAs is negative in some patients and ease of use/availability of ligand can be a problem and lastly, newer groups of patients are being considered for possible SSTA treatment with newer SSTA related compounds. AREAS COVERED: In this perspective, the authors briefly review recent advances which are resulting or may result in new and emerging SSTAs that show promise in future use in NEN patients. It includes identification of both new or promising non-radioactive SSTA (cold SSTA) and radiolabeled SSTAs which could replace existing SSTAs now currently used, as well as new protocols for the new/promising SSTAs, or for existing SSTAs. These new/promising SSTAs/ or new/promising uses of these SSTAs include both chemically completely new SSTAs; pharmacologically new in their actions such as nonpeptide in nature; antagonist rather than agonist; longer acting in duration; and oral rather than parenteral administration. For peptide receptor radionuclide therapy (PRRT)/ imaging with radiolabeled SSTAs new developments covered include new promising SSTAs coupled to beta-emitters, alpha emitters, administered with radio-sensitizing agents, and new, promising protocols for PRRT retreatment, personalized treatment, adjuvant treatment or treatment of pediatric patients. They also include combinations of new/promising/exiting SSTAs both radiolabeled for PRRT or non-radiolabeled for tumor cytotoxic /and/or inhibitory effects formed by administration of the SSTA with other cytotoxic agents such as mTor inhibitors, chemotherapeutic agents, Tyrosine Kinase Inhibitors (TKIs), angiogenesis inhibitors, nonradioactive-SSTAs with PRRT or with immune therapy. EXPERT OPINION: This review of new and promising SSTR therapies involving both radiolabeled and non-radiolabeled for the future treatment of NENs strongly supports the conclusion that in the future SSTR- based drugs will continue to play prominent roles in all aspects of the management of NENs. This conclusion extends to the use of SST ligands to image these tumors to establish the location of the primary, location and extent of metastatic disease and the presence of SSTRs on the tumor for possible PRRT therapy; to the control of hormonal symptoms in F-NENs such as the carcinoid syndrome, vasoactive-intestinal-peptide- secreting (VIPomas)/ Adrenocortotropin-secreting(ACTHomas), etc. and to anti-proliferative roles for the treatment of advanced disease with both non-radioactive SSTAs, as well with PRRT with radiolabeled SSTAs and likely with novel new non-radiolabeled cytotoxic SSTAs. Numerous recent studies firmly establish these conclusions, all of which are reviewed here; and they will likely be further supported by additional studies that are in progress and also cited here.