Pancreatic endocrine disorders and multiple endocrine neoplasia

2020 ◽  
pp. 2449-2463
Author(s):  
B. Khoo ◽  
T.M. Tan ◽  
S.R. Bloom
Keyword(s):  
Kinase Inhibitors ◽  
Neuroendocrine Tumours ◽  
Mammalian Target Of Rapamycin ◽  
Peptide Receptor Radionuclide Therapy ◽  
Mtor Inhibitors ◽  
Somatostatin Analogues ◽  
Endocrine Disorders ◽  
Pancreatic Neuroendocrine Tumours ◽  
Islet Cell Tumours ◽  
Cancer Syndromes

Pancreatic neuroendocrine tumours (islet-cell tumours) are rare and usually sporadic, but they may be associated with complex familial endocrine cancer syndromes. Recognized types of pancreatic neuroendocrine tumours are those that are non-functioning (often advanced at diagnosis and presenting with mass effects due to the absence of symptoms attributable to hormone hypersecretion), insulinoma (the most frequent type), and others including gastrinoma, VIPoma, and glucagonoma. The following should be considered in addition to the symptomatic treatments: surgical resection—the only curative treatment, but not possible in many cases; tyrosine kinase inhibitors which inhibit specific kinases involved in tumour cell proliferation, growth, and angiogenesis; mammalian Target of Rapamycin (mTOR) inhibitors; peptide-receptor radionuclide therapy (radiolabelled somatostatin analogues).

Pancreatic endocrine disorders and multiple endocrine neoplasia

2010 ◽  
pp. 1976-1986
Author(s):  
N.M. Martin ◽  
S.R. Bloom
Keyword(s):  
Islet Cell ◽  
Multiple Endocrine Neoplasia ◽  
Neuroendocrine Tumours ◽  
Endocrine Disorders ◽  
Frequent Type ◽  
Endocrine Neoplasia ◽  
Pancreatic Neuroendocrine Tumours ◽  
Islet Cell Tumours ◽  
Cancer Syndromes

Pancreatic neuroendocrine tumours (islet cell tumours) are rare and usually sporadic, but they may be associated with complex familial endocrine cancer syndromes. Recognized types of pancreatic neuroendocrine tumours are those that are nonfunctioning (often advanced at diagnosis due to the absence of symptoms attributable to hormone hypersecretion), insulinoma (the most frequent type, see ...

Peptide Receptor Radionuclide Therapy for Pancreatic Neuroendocrine Tumours

2019 ◽  
Vol 12 (2) ◽  
pp. 126-134 ◽  
Author(s):  
Shahad Alsadik ◽  
Siraj Yusuf ◽  
Adil AL-Nahhas
Keyword(s):  
Side Effects ◽  
Effective Treatment ◽  
Radionuclide Therapy ◽  
Neuroendocrine Tumours ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Treatment Modalities ◽  
Effective Treatment Option ◽  
Peptide Receptor ◽  
Pancreatic Neuroendocrine Tumours

Background: The incidence of pancreatic Neuroendocrine Tumours (pNETs) has increased considerably in the last few decades. The characteristic features of this tumour and the development of new investigative and therapeutic methods had a great impact on its management. Objective: The aim of this review is to investigate the outcome of Peptide Receptor Radionuclide Therapy (PRRT) in the treatment of pancreatic neuroendocrine tumours. Methods: A comprehensive literature search strategy was used based on two databases (SCOPUS, and PubMed). We considered all studies published in English, evaluating the use of PRRT (177Luteciuim- DOTA-conjugated peptides and 90Yetrium- DOTA- conjugated peptides) in the treatment of pancreatic neuroendocrine tumours as a standalone entity or as a subgroup within the wider category of Gastroenteropancreatic Neuroendocrine Tumours (GEP NETs). Results: PRRT was found to be an effective treatment modality as a monotherapy or in combination with other therapies in the treatment of non-operable and metastatic pNETs where other options are limited. Complete response was reported to be between 2-6% while partial response was achieved in up to 60% of cases. Survival analysis was also impressive. Progression Free Survival (PFS) reached a mean of 34 months and Overall Survival (OS) of 53 months. PRRT also proved to improve patients’ Quality of Life (QoL). Acute and sub-acute side effects like nephrotoxicity and haematotoxicity are usually mild and reversible. Conclusion: PRRT is well tolerated and effective treatment option for non-operable and/or metastatic pNETs. Side effects are usually mild and reversible. Larger randomized controlled trails need to be done to compare PRRT with other treatment modalities and to provide more detailed guidelines regarding patient selections, the choice of PRRT, follow up and response assessment to maximum potential benefit.

scholarly journals mTOR-targeted cancer therapy: great target but disappointing clinical outcomes, why?

2020 ◽  
Author(s):  
Shi-Yong Sun
Keyword(s):  
Cancer Therapy ◽  
Kinase Inhibitors ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Inhibitors ◽  
Targeted Cancer Therapy ◽  
Biological Functions ◽  
New Findings ◽  
Survival Signaling ◽  
Mtor Complex 1

Abstract The mammalian target of rapamycin (mTOR) critically regulates several essential biological functions, such as cell growth, metabolism, survival, and immune response by forming two important complexes, namely, mTOR complex 1 (mTORC1) and complex 2 (mTORC2). mTOR signaling is often dysregulated in cancers and has been considered an attractive cancer therapeutic target. Great efforts have been made to develop efficacious mTOR inhibitors, particularly mTOR kinase inhibitors, which suppress mTORC1 and mTORC2; however, major success has not been achieved. With the strong scientific rationale, the intriguing question is why cancers are insensitive or not responsive to mTOR-targeted cancer therapy in clinics. Beyond early findings on induced activation of PI3K/Akt, MEK/ERK, and Mnk/eIF4E survival signaling pathways that compromise the efficacy of rapalog-based cancer therapy, recent findings on the essential role of GSK3 in mediating cancer cell response to mTOR inhibitors and mTORC1 inhibition-induced upregulation of PD-L1 in cancer cells may provide some explanations. These new findings may also offer us the opportunity to rationally utilize mTOR inhibitors in cancer therapy. Further elucidation of the biology of complicated mTOR networks may bring us the hope to develop effective therapeutic strategies with mTOR inhibitors against cancer.

New Frontiers in Mucositis

2012 ◽  
pp. 545-551 ◽  
Author(s):  
Douglas E. Peterson ◽  
Dorothy M. Keefe ◽  
Stephen T. Sonis
Keyword(s):  
Kinase Inhibitors ◽  
Management Strategies ◽  
Mammalian Target Of Rapamycin ◽  
Cancer Therapeutics ◽  
Mtor Inhibitors ◽  
Mucosal Injury ◽  
Mucosal Damage ◽  
Nucleotide Polymorphisms ◽  
Oncology Patient ◽  
Novel Technologies

Overview: Mucositis is among the most debilitating side effects of radiotherapy, chemotherapy, and targeted anticancer therapy. Research continues to escalate regarding key issues such as etiopathology, incidence and severity across different mucosae, relationships between mucosal and nonmucosal toxicities, and risk factors. This approach is being translated into enhanced management strategies. Recent technology advances provide an important foundation for this continuum. For example, evolution of applied genomics is fostering development of new algorithms to rapidly screen genomewide single-nucleotide polymorphisms (SNPs) for patient-associated risk prediction. This modeling will permit individual tailoring of the most effective, least toxic treatment in the future. The evolution of novel cancer therapeutics is changing the mucositis toxicity profile. These agents can be associated with unique mechanisms of mucosal damage. Additional research is needed to optimally manage toxicity caused by agents such as mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors, without reducing antitumor effect. There has similarly been heightened attention across the health professions regarding clinical practice guidelines for mucositis management in the years following the first published guidelines in 2004. New opportunities exist to more effectively interface this collective guideline portfolio by capitalizing upon novel technologies such as an Internet-based Wiki platform. Substantive progress thus continues across many domains associated with mucosal injury in oncology patients. In addition to enhancing oncology patient care, these advances are being integrated into high-impact educational and scientific venues including the National Cancer Institute Physician Data Query (PDQ) portfolio as well as a new Gordon Research Conference on mucosal health and disease scheduled for June 2013.

scholarly journals Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs)

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1988
Author(s):  
Vera G. Megdanova-Chipeva ◽  
Angela Lamarca ◽  
Alison Backen ◽  
Mairéad G. McNamara ◽  
Jorge Barriuso ◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Systemic Treatment ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
Peptide Receptor Radionuclide Therapy ◽  
Treatment Selection ◽  
Phase Iii ◽  
Current Evidence ◽  
Rare Tumours ◽  
Pancreatic Neuroendocrine Tumours

Pancreatic neuroendocrine tumours (PanNETs) are rare diseases and a good example of how research is not only feasible, but also of crucial importance in the scenario of rare tumours. Many clinical trials have been performed over the past two decades expanding therapeutic options for patients with advanced PanNETs. Adequate management relies on optimal selection of treatment, which may be challenging for clinicians due to the fact that multiple options of therapy are currently available. A number of therapies already exist, which are supported by data from phase III studies, including somatostatin analogues and targeted therapies (sunitinib and everolimus). In addition, chemotherapy remains an option, with temozolomide and capecitabine being one of the most popular doublets to use. Peptide receptor radionuclide therapy was successfully implemented in patients with well-differentiated gastro-entero-pancreatic neuroendocrine tumours, but with certain questions waiting to be solved for the management of PanNETs. Finally, the role of immunotherapy is still poorly understood. In this review, the data supporting current systemic treatment options for locally advanced or metastatic PanNETs are summarized. Strategies for treatment selection in patients with PanNETs based on patient, disease, or drug characteristics is provided, as well as a summary of current evidence on prognostic and predictive biomarkers. Future perspectives are discussed, focusing on current and forthcoming challenges and unmet needs of patients with these rare tumours.

scholarly journals Dopamine agonist resistant prolactinomas: any alternative medical treatment?

Pituitary ◽  
2019 ◽  
Vol 23 (1) ◽  
pp. 27-37 ◽  
Author(s):  
P. Souteiro ◽  
N. Karavitaki
Keyword(s):  
Kinase Inhibitors ◽  
Mammalian Target Of Rapamycin ◽  
Somatostatin Analogues ◽  
Cytotoxic Agents ◽  
Tumor Control ◽  
Medical Treatments ◽  
Secondary Resistance ◽  
Optimal Outcomes ◽  
Clinical Scenarios

Abstract Consensus guidelines recommend dopamine agonists (DAs) as the mainstay treatment for prolactinomas. In most patients, DAs achieve tumor shrinkage and normoprolactinemia at well tolerated doses. However, primary or, less often, secondary resistance to DAs may be also encountered representing challenging clinical scenarios. This is particularly true for aggressive prolactinomas in which surgery and radiotherapy may not achieve tumor control. In these cases, alternative medical treatments have been considered but data on their efficacy should be interpreted within the constraints of publication bias and of lack of relevant clinical trials. The limited reports on somatostatin analogues have shown conflicting results, but cases with optimal outcomes have been documented. Data on estrogen modulators and metformin are scarce and their usefulness remains to be evaluated. In many aggressive lactotroph tumors, temozolomide has demonstrated optimal outcomes, whereas for other cytotoxic agents, tyrosine kinase inhibitors and for inhibitors of mammalian target of rapamycin (mTOR), higher quality evidence is needed. Finally, promising preliminary results from in vitro and animal reports need to be further assessed and, if appropriate, translated in human studies.

scholarly journals Sequence of therapy and survival in patients with advanced pancreatic neuroendocrine tumours

2020 ◽  
Vol 27 (4) ◽  
Author(s):  
E. S. Tsang ◽  
J.M. Loree ◽  
C. Speers ◽  
H.F. Kennecke
Keyword(s):  
Neuroendocrine Tumours ◽  
Progression Free Survival ◽  
Somatostatin Analogues ◽  
Treatment Modalities ◽  
Primary Role ◽  
First Line ◽  
Optimal Sequence ◽  
Systemic Treatments ◽  
Pancreatic Neuroendocrine Tumours ◽  
Line Of Therapy

Background Pancreatic neuroendocrine tumours (pnets) often present as advanced disease. The optimal sequence of therapy is unknown. Methods Sequential patients with advanced pnets referred to BC Cancer between 2000 and 2013 who received 1 or more treatment modalities were reviewed, and treatment patterns, progression-free survival (pfs), and overall survival (os) were characterized. Systemic treatments included chemotherapy, small-molecule therapy, and peptide receptor radiotherapy. Results In 66 cases of advanced pnets, median patient age was 61.2 years (25%–75% interquartile range: 50.8–66.2 years), and men constituted 47% of the group. First-line therapies were surgery (36%), chemotherapy (33%), and somatostatin analogues (32%). Compared with first-line systemic therapy, surgery in the first line was associated with increased pfs and os (20.6 months vs. 6.3 months and 100.3 months vs. 30.5 months respectively, p < 0.05). In 42 patients (64%) who received more than 1 line of therapy, no difference in os or pfs between second-line therapies was observed. Conclusions Our results confirm the primary role of surgery for advanced pnets. New systemic treatments will further increase options.

scholarly journals Immunotherapy in Metastatic Renal Cell Carcinoma: A Comprehensive Review

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Rachna Raman ◽  
Daniel Vaena
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Mammalian Target Of Rapamycin ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Immune Therapies ◽  
Localized Renal Cell Carcinoma ◽  
Metastatic Rcc

Localized renal cell carcinoma (RCC) is often curable by surgery alone. However, metastatic RCC is generally incurable. In the 1990s, immunotherapy in the form of cytokines was the mainstay of treatment for metastatic RCC. However, responses were seen in only a minority of highly selected patients with substantial treatment-related toxicities. The advent of targeted agents such as vascular endothelial growth factor tyrosine kinase inhibitors VEGF-TKIs and mammalian target of rapamycin (mTOR) inhibitors led to a change in this paradigm due to improved response rates and progression-free survival, a better safety profile, and the convenience of oral administration. However, most patients ultimately progress with about 12% being alive at 5 years. In contrast, durable responses lasting 10 years or more are noted in a minority of those treated with cytokines. More recently, an improved overall survival with newer forms of immunotherapy in other malignancies (such as melanoma and prostate cancer) has led to a resurgence of interest in immune therapies in metastatic RCC. In this review we discuss the rationale for immunotherapy and recent developments in immunotherapeutic strategies for treating metastatic RCC.

scholarly journals Predictive factors of response to mTOR inhibitors in neuroendocrine tumours

2015 ◽  
Vol 23 (3) ◽  
pp. R173-R183 ◽  
Author(s):  
Maria Chiara Zatelli ◽  
Giuseppe Fanciulli ◽  
Pasqualino Malandrino ◽  
Valeria Ramundo ◽  
Antongiulio Faggiano ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Neuroendocrine Tumours ◽  
Somatostatin Analogs ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Free Survival ◽  
Development Of Resistance ◽  
Imaging Markers ◽  
Intensive Investigation ◽  
Recent Demonstration

Medical treatment of neuroendocrine tumours (NETs) has drawn a lot of attention due to the recent demonstration of efficacy of several drugs on progression-free survival, including somatostatin analogs, small tyrosine kinase inhibitors and mTOR inhibitors (or rapalogs). The latter are approved as therapeutic agents in advanced pancreatic NETs and have been demonstrated to be effective in different types of NETs, with variable efficacy due to the development of resistance to treatment. Early detection of patients that may benefit from rapalogs treatment is of paramount importance in order to select the better treatment and avoid ineffective and expensive treatments. Predictive markers for therapeutic response are under intensive investigation, aiming at a tailored patient management and more appropriate resource utilization. This review summarizes the available data on the tissue, circulating and imaging markers that are potentially predictive of rapalog efficacy in NETs.

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