scholarly journals Targeted Cancer Therapy: What’s New in the Field of Neuroendocrine Neoplasms?

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1701
Author(s):  
Anna La Salvia ◽  
Paula Espinosa-Olarte ◽  
Maria Del Carmen Riesco-Martinez ◽  
Beatriz Anton-Pascual ◽  
Rocío Garcia-Carbonero
Keyword(s):  
Treatment Options ◽  
Somatostatin Receptors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Somatostatin Analogues ◽  
Neuroendocrine Neoplasms ◽  
Antiangiogenic Agents ◽  
Drug Conjugates ◽  
Therapeutic Drugs ◽  
Anatomic Distribution ◽  
Pancreatic Origin

Neuroendocrine tumors (NETs) are a heterogeneous family of neoplasms of increasing incidence and high prevalence due to their relatively indolent nature. Their wide anatomic distribution and their characteristic ability to secrete hormonally active substances pose unique challenges for clinical management. They are also characterized by the common expression of somatostatin receptors, a target that has been extremely useful for diagnosis and treatment (i.e., somatostatin analogues (SSAs) and peptide-receptor radionuclide therapy (PRRT)). Chemotherapy is of limited use for NETs of non-pancreatic origin, and the only approved targeted agents for advanced progressive NETs are sunitinib for those of pancreatic origin, and everolimus for lung, gastrointestinal and pancreatic primaries. Despite recent therapeutic achievements, thus, systemic treatment options remain limited. In this review we will discuss the state-of-the-art targeted therapies in the field of NETs, and also future perspectives of novel therapeutic drugs or strategies in clinical development, including recently presented results from randomized trials of yet unapproved antiangiogenic agents (i.e., pazopanib, surufatinib and axitinib), PRRT including both approved radiopharmaceuticals (177Lu-Oxodotreotide) and others in development (177Lu-Edotreotide, 177Lu-Satoreotide Tetraxetan), immunotherapy and other innovative targeted strategies (antibody-drug conjugates, bites,…) that shall soon improve the landscape of personalized treatment options in NET patients.

scholarly journals Neuroendocrine Carcinoma of the Uterine Cervix: A Clinicopathologic and Immunohistochemical Study with Focus on Novel Markers (Sst2–Sst5)

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1211
Author(s):  
Frediano Inzani ◽  
Angela Santoro ◽  
Giuseppe Angelico ◽  
Angela Feraco ◽  
Saveria Spadola ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Target Therapy ◽  
Somatostatin Receptors ◽  
Neuroendocrine Differentiation ◽  
Large Cell ◽  
Cell Types ◽  
Somatostatin Analogues ◽  
Small Cell ◽  
Neuroendocrine Neoplasms ◽  
Neuroendocrine Carcinomas

Background. Gynecological neuroendocrine neoplasms (NENs) are extremely rare, accounting for 1.2–2.4% of the NENs. The aim of this study was to test cervical NENs for novel markers of potential utility for differential diagnosis and target therapy. Methods. All cases of our center (n = 16) were retrieved and tested by immunohistochemistry (IHC) for 12 markers including markers of neuroendocrine differentiation (chromogranin A, synaptophysin, CD56), transcription factors (CDX2 and TTF1), proteins p40, p63, p16INK4a, and p53, somatostatin receptors subtypes (SST2-SST5) and the proliferation marker Ki67 (MIB1). Results. All cases were poorly differentiated neuroendocrine carcinomas (NECs), 10 small cell types (small cell–neuroendocrine carcinomas, SCNECs) and 6 large cell types (large cell–neuroendocrine carcinomas, LCNECs); in 3 cases a predominant associated adenocarcinoma component was observed. Neuroendocrine cancer cells expressed at least 2 of the 3 tested neuroendocrine markers; p16 was intensely expressed in 14 (87.5%) cases; SST5 in 11 (56.25%, score 2–3, in 9 cases); SST2 in 8 (50%, score 2–3 in 8), CDX2 in 8 (50%), TTF1 in 5 (31.25%), and p53 in 1 case (0.06%). P63 and p40 expressions were negative, with the exception of one case that showed moderate expression for p63. Conclusions. P40 is a more useful marker for the differential diagnosis compared to squamous cell carcinoma. Neither CDX2 nor TTF1 expression may help the differential diagnosis versus potential cervical metastasis. P16 expression may suggest a cervical origin of NEC; however, it must be always integrated by clinical and instrumental data. The expression of SST2 and SST5 could support a role for SSAs (Somatostatin Analogues) in the diagnosis and therapy of patients with cervical NECs.

scholarly journals Somatostatin and Somatostatin Receptors: From Signaling to Clinical Applications in Neuroendocrine Neoplasms

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1810
Author(s):  
Maria Isabel del Olmo-Garcia ◽  
Stefan Prado-Wohlwend ◽  
Alexia Andres ◽  
Jose M. Soriano ◽  
Pilar Bello ◽  
...  
Keyword(s):  
Cell Surface ◽  
Treatment Options ◽  
Somatostatin Receptors ◽  
Clinical Applications ◽  
The Body ◽  
Neuroendocrine Cells ◽  
Molecular Characteristics ◽  
Neuroendocrine Neoplasms ◽  
Near Future ◽  
Potential Biomarkers

Neuroendocrine neoplasms (NENs) are heterogeneous neoplasms which arise from neuroendocrine cells that are distributed widely throughout the body. Although heterogenous, many of them share their ability to overexpress somatostatin receptors (SSTR) on their cell surface. Due to this, SSTR and somatostatin have been a large subject of interest in the discovery of potential biomarkers and treatment options for the disease. The aim of this review is to describe the molecular characteristics of somatostatin and somatostatin receptors and its application in diagnosis and therapy on patients with NENs as well as the use in the near future of somatostatin antagonists.

scholarly journals GEP–NETs UPDATE: Biotherapy for neuroendocrine tumours

2015 ◽  
Vol 172 (1) ◽  
pp. R31-R46 ◽  
Author(s):  
T Alonso-Gordoa ◽  
J Capdevila ◽  
E Grande
Keyword(s):  
Neuroendocrine Tumours ◽  
Symptomatic Relief ◽  
Somatostatin Receptors ◽  
Treatment Strategies ◽  
Mtor Inhibitors ◽  
Somatostatin Analogues ◽  
Antiangiogenic Agents ◽  
Tumour Control ◽  
Control Growth ◽  
Long Time

Neuroendocrine tumours (NETs) represent a less frequent and heterogeneous group of tumours, which has experienced, in recent years, a significant increase in effective therapeutic possibilities overcoming the disappointing results from chemotherapy. Initial improvements in treatment strategies came from somatostatin analogues (SSAs) that have widely demonstrated a significant improvement in symptomatic relief and tumour control growth by a complex mechanism of action over cell survival, angiogenesis and immunomodulation. Recent investigations have pointed out novel SSAs with a wider binding profile (pasireotide), chimeric molecules against somatostatin receptors and dopamine receptors and the combination with targeted agents, such as mTOR inhibitors or antiangiogenic agents. Immunotherapy is the second cornerstone in NET treatment and has been represented with interferon alpha for a long time, with a demonstrated activity on tumour and clinical response. Its less manageable adverse events have limited its usage. However, different checkpoints in immune system regulation have been effectively targeted in different solid tumours, and novel approaches are currently arising in NETs. In conclusion, biotherapy remains an active treatment strategy for initial approach in patients with NETs. Further investigation on patients' selection, molecular profiles, treatment sequence or combination and optimisation of current and novel biotherapy agents is required.

Systemic Therapy for Neuroendocrine Neoplasms

2019 ◽  
Vol 03 (01) ◽  
pp. 063-070
Author(s):  
David Chan ◽  
Simron Singh
Keyword(s):  
Carcinoid Syndrome ◽  
Systemic Treatment ◽  
Histological Grade ◽  
Delayed Diagnosis ◽  
Peptide Receptor Radionuclide Therapy ◽  
Somatostatin Analogues ◽  
Neuroendocrine Neoplasms ◽  
Ongoing Research ◽  
Disease Characteristics ◽  
Grade 3

AbstractNeuroendocrine neoplasms (NENs) are heterogeneous malignancies which are becoming more common. Systemic treatment is considered for patients with advanced disease, and treatment decisions are often driven by the histological grade of the tumor and the site of primary. Somatostatin analogues are the first-line option of choice for gastroenteropancreatic NENs but subsequent options may include the targeted agents everolimus and sunitinib as well as peptide receptor radionuclide therapy. Telotristat is a new option for the treatment of refractory carcinoid syndrome diarrhea. Chemotherapy is infrequently used for Grade 1 to 2 NENs (except for the combination of capecitabine and temozolomide) but is the mainstay of therapy for Grade 3 neuroendocrine carcinomas. Bronchial NENs are graded differently and there are few proven options for systemic treatment. Optimal integration of available systemic therapies, the timely recognition of tumor heterogeneity, and the use of nuclear medicine are areas of ongoing research. Finally, the patient experience is impacted by factors such as delayed diagnosis and symptoms of carcinoid syndrome. Clinicians need to account for patient priorities and disease characteristics to individualize therapy choices for patients with advanced NEN.

scholarly journals Advances in the Management of Medullary Thyroid Carcinoma: Focus on Peptide Receptor Radionuclide Therapy

2020 ◽  
Vol 9 (11) ◽  
pp. 3507
Author(s):  
Erika Grossrubatscher ◽  
Giuseppe Fanciulli ◽  
Luca Pes ◽  
Franz Sesti ◽  
Carlotta Dolci ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Radionuclide Therapy ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Peptide Receptor Radionuclide Therapy ◽  
Neuroendocrine Neoplasms ◽  
Medullary Thyroid ◽  
Peptide Receptor

Effective treatment options in advanced/progressive/metastatic medullary thyroid carcinoma (MTC) are currently limited. As in other neuroendocrine neoplasms (NENs), peptide receptor radionuclide therapy (PRRT) has been used as a therapeutic option in MTC. To date, however, there are no published reviews dealing with PRRT approaches. We performed an in-depth narrative review on the studies published in this field and collected information on registered clinical trials related to this topic. We identified 19 published studies, collectively involving more than 200 patients with MTC, and four registered clinical trials. Most cases of MTC were treated with PRRT with somatostatin analogues (SSAs) radiolabelled with 90 yttrium (90Y) and 177 lutetium (177Lu). These radiopharmaceuticals show efficacy in the treatment of patients with MTC, with a favourable radiological response (stable disease, partial response or complete response) in more than 60% of cases, coupled with low toxicity. As MTC specifically also expresses cholecystokinin receptors (CCK2Rs), PRRT with this target has also been tried, and some randomised trials are ongoing. Overall, PRRT seems to have an effective role and might be considered in the therapeutic strategy of advanced/progressive/metastatic MTC.

scholarly journals Somatostatin receptor endoradiotherapy of neuroendocrine tumors: experience in Hungarian patients

2011 ◽  
Vol 152 (10) ◽  
pp. 392-397 ◽  
Author(s):  
Péter Reismann ◽  
Zoltán Kender ◽  
Gabriella Dabasi ◽  
Lídia Sréter ◽  
Károly Rácz ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Somatostatin Analogues ◽  
Theoretical Background ◽  
Neuroendocrine Cells ◽  
Peptide Receptor ◽  
The University

Beside conventional therapies for the treatment of neuroendocrine tumors, a new therapeutical approach, peptide receptor radionuclide therapy has been developed recently. There are two important features which make this therapy feasible: somatostatin receptors are strongly over-expressed in most neuroendocrine tumors resulting in a high tumor-to-background ratio and internalization of the somatostatin-receptor complex in neuroendocrine cells. Due to these features, neuroendocrine tumors can be treated with radiolabelled somatostatin analogues. For peptide receptor radionuclide therapy, somatostatin analogues are conjugated to a chelator that can bind a radionuclide. The most frequently used radionuclides for neuroendocrine tumor treatment are the β-emitter Yttrium-90 (90Y) and the β+γ emitter Lutetium-177 (177Lu). Candidates for somatostatin receptor endoradiotherapy are patients with progressive, metastatic, somatostatin-receptor positive neuroendocrine tumors. Many patients have been successively treated with this approach: according to international results major remission can be achieved in 25% of the cases. Although this therapy is still unavailable in Hungary, Hungarian patients can be treated with somatostatin receptor endoradiotherapy with financial support from the National Health Fund in a co-operation with the University of Basel since 2005. During the past 5 years, 51 Hungarian patients have been treated with this therapy. This review briefly summarizes the theoretical background, indications, effectiveness and side effects of somatostatin receptor endoradiotherapy and the authors present the first data obtained from Hungarian patients. Orv. Hetil., 2011, 152, 392–397.

Gamma Emitters in Pancreatic Endocrine Tumors Imaging in the PET Era: Is there a Clinical Space for 99mTc-peptides?

2019 ◽  
Vol 12 (2) ◽  
pp. 156-170 ◽  
Author(s):  
Vittorio Briganti ◽  
Vincenzo Cuccurullo ◽  
Giuseppe Danilo Di Stasio ◽  
Luigi Mansi
Keyword(s):  
Somatostatin Receptors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Cost Effective ◽  
Daily Practice ◽  
Cell Types ◽  
Somatostatin Analogues ◽  
Neoplastic Cell ◽  
Endocrine Tumors ◽  
Clinical Role ◽  
Pancreatic Endocrine Tumors

Background: Pancreatic Neuroendocrine Tumors (PNETs) are rare neoplasms, sporadic or familial, even being part of a syndrome. Their diagnosis is based on symptoms, hormonal disorders or may be fortuitous. The role of Nuclear Medicine is important, mainly because of the possibility of a theranostic strategy. This approach is allowed by the availability of biochemical agents, which may be labeled with radionuclides suitable for diagnostic or therapeutic purposes, showing almost identical pharmacokinetics. The major role for radiopharmaceuticals is connected with radiolabeled Somatostatin Analogues (SSA), since somatostatin receptors are highly expressed on some of the neoplastic cell types. Discussion: Nowadays, in the category of radiolabeled SSA, although 111In-pentetreotide, firstly commercially proposed, is still used, the best choice for diagnosis is related to the so called DOTAPET radiotracers labeled with 68-Gallium (Ga), such as 68Ga-DOTATATE, 68Ga-DOTANOC, and 68Ga-DOTATOC. More recently, labeling with 64-Copper (Cu) (64Cu-DOTATATE) has also been proposed. In this review, we discuss the clinical interest of a SAA (Tektrotyd©) radiolabeled with 99mTc, a gamma emitter with better characteristics, with respect to 111Indium, radiolabeling Octreoscan ©. By comparing both pharmacokinetics and pharmacodynamics of Octreoscan©, Tektrotyd© and PET DOTA-peptides, on the basis of literature data and of our own experience, we tried to highlight these topics to stimulate further studies, individuating actual clinical indications for all of these radiotracers. Conclusion: In our opinion, Tektrotyd© could already find its applicative dimension in the daily practice of NETs, either pancreatic or not, at least in centers without a PET/CT or a 68Ga generator. Because of wider availability, a lower cost, and a longer decay, compared with respect to peptides labeled with 68Ga, it could be also proposed, in a theranostic context, for a dosimetry evaluation of patients undergoing Peptide Receptor Radionuclide Therapy (PRRT), and for non-oncologic indications of radiolabelled SSA. In this direction, and for a more rigorous cost/effective evaluation, more precisely individuating its clinical role, further studies are needed.

scholarly journals WOMEN IN CANCER THEMATIC REVIEW: Systemic therapies in neuroendocrine tumors and novel approaches toward personalized medicine

2016 ◽  
Vol 23 (11) ◽  
pp. T135-T154 ◽  
Author(s):  
Marianne E Pavel ◽  
Christine Sers
Keyword(s):  
Personalized Medicine ◽  
Neuroendocrine Tumors ◽  
Kinase Inhibitor ◽  
Treatment Options ◽  
Objective Response ◽  
Peptide Receptor Radionuclide Therapy ◽  
Response Duration ◽  
Somatostatin Analogues ◽  
Molecular Alterations ◽  
Therapeutic Decision Making

Neuroendocrine tumors (NETs) are a group of heterogenous neoplasms. Evidence-based treatment options for antiproliferative therapy include somatostatin analogues, the mTOR inhibitor everolimus, the multiple tyrosine kinase inhibitor sunitinib and peptide receptor radionuclide therapy with 177-Lu-octreotate. In the absence of definite predictive markers, therapeutic decision making follows clinical and pathological criteria. As objective response rates with targeted drugs are rather low, and response duration is limited in most patients, numerous combination therapies targeting multiple pathways have been explored in the field. Upfront combination of drugs, however, is associated with increasing toxicity and has shown little benefit. Major advancements in the molecular understanding of NET based on genomic, epigenomic and transcriptomic analysis have been achieved with prognostic and therapeutic impact. New insight into molecular alterations has paved the way to biomarker-driven clinical trials and may facilitate treatment stratification toward personalized medicine in the near future. However, an improved understanding of the complexity of pathway interactions is required for successful treatment. A systems biology approach is one of the tools that may help to achieve this endeavor.

scholarly journals Chemotherapy in NEN: still has a role?

2021 ◽  
Author(s):  
Paula Espinosa-Olarte ◽  
Anna La Salvia ◽  
Maria C. Riesco-Martinez ◽  
Beatriz Anton-Pascual ◽  
Rocio Garcia-Carbonero
Keyword(s):  
Therapeutic Strategy ◽  
Treatment Options ◽  
Somatostatin Receptor ◽  
Treatment Algorithm ◽  
Somatostatin Analogues ◽  
Neuroendocrine Neoplasms ◽  
Primary Tumor Site ◽  
Novel Drugs ◽  
Well Differentiated ◽  
Extent Of Disease

AbstractNeuroendocrine neoplasms (NENs) comprise a broad spectrum of tumors with widely variable biological and clinical behavior. Primary tumor site, extent of disease, tumor differentiation and expression of so matostatin receptors, proliferation and growth rates are the major prognostic factors that determine the therapeutic strategy. Treatment options for advanced disease have considerably expanded in recent years, particularly for well differentiated tumors (NETs). Novel drugs approved over the past decade in this context include somatostatin analogues and 177Lu-oxodotreotide for somatostatin-receptor-positive gastroenteropancreatic (GEP) NETs, sunitinib for pancreatic NETs (P-NETs), and everolimus for P-NETs and non-functioning lung or gastrointestinal NETs. Nevertheless, chemotherapy remains an essential component of the treatment armamentarium of patients with NENs, particularly of patients with P-NETs or those with bulky, symptomatic or rapidly progressive tumors (generally G3 or high-G2 NENs). In this manuscript we will comprehensively review available evidence related to the use of chemotherapy in lung and GEP NENs and will critically discuss its role in the treatment algorithm of this family of neoplasms.

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