c-MET inhibition: novel treatment for sporadic and MEN1-associated GEP NETs

Lee, Maya Elena; Tepede, Aisha; Mandl, Adel; Weinstein, Lee S.; Rivero, Jaydira Del; Agarwal, Sunita K.; Blau, Jenny

doi:10.1530/jme-20-0020

Cited by 5 publications

(4 citation statements)

References 92 publications

(102 reference statements)

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“…c-MET is a tyrosine kinase receptor for hepatocyte growth factor found to be overexpressed in Pan-NETs, especially as consequence of menin loss [207]. The TKI cabozantinib, a c-MET and VEGFR2 inhibitor, was recently used in a clinical trial (NCT01466036) in patients with advanced neuroendocrine tumors showing improved PFS [208], supporting c-MET inhibition as a therapeutic target for GEP-NETs [209]. Finally, the IGF-1 receptor is usually overexpressed in NETs, especially in functioning ones.…”

Section: Novel Therapeutic Approaches and Future Directionsmentioning

confidence: 99%

Molecular Pathology of Well-Differentiated Gastro-entero-pancreatic Neuroendocrine Tumors

et al. 2021

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Well differentiated neuroendocrine tumors (NETs) arising in the gastrointestinal and pancreaticobiliary system are the most common neuroendocrine neoplasms. Studies of the molecular basis of these lesions have identified genetic mutations that predispose to familial endocrine neoplasia syndromes and occur both as germline events and in sporadic tumors. The mutations often involve epigenetic regulators rather than the oncogenes and tumor suppressors that are affected in other malignancies. Somatic copy number alterations and miRNAs have also been implicated in the development and progression of some of these tumors. The molecular profiles differ by location, but many are shared by tumors in other sites, including those outside the gastroenteropancreatic system. The approach to therapy relies on both the neuroendocrine nature of these tumors and the identification of specific alterations that can serve as targets for precision oncologic approaches.

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Section: Novel Therapeutic Approaches and Future Directionsmentioning

confidence: 99%

Molecular Pathology of Well-Differentiated Gastro-entero-pancreatic Neuroendocrine Tumors

et al. 2021

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“…In particular, up to 40% of somatic pNETs have mutations in either the apoptotic regulator DAXX (death-domain-associated protein) or the chromatin modifier ATRX (a thalassemia/intellectual disability syndrome X-linked) where they promote ALT and chromosomal instability (40,42,43). These alternations in MEN1, DAXX and ATRX have led to the hypothesis of molecular subtypes, which may confer both therapeutic interventions and possible survival benefit (40,44).…”

Section: Multiple Endocrine Neoplasia Type 1 Syndrome (Men1)mentioning

confidence: 99%

Familial Hyperparathyroidism

Blau

Simonds

2021

Front. Endocrinol.

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Regulation of the serum calcium level in humans is achieved by the endocrine action of parathyroid glands working in concert with vitamin D and a set of critical target cells and tissues including osteoblasts, osteoclasts, the renal tubules, and the small intestine. The parathyroid glands, small highly vascularized endocrine organs located behind the thyroid gland, secrete parathyroid hormone (PTH) into the systemic circulation as is needed to keep the serum free calcium concentration within a tight physiologic range. Primary hyperparathyroidism (HPT), a disorder of mineral metabolism usually associated with abnormally elevated serum calcium, results from the uncontrolled release of PTH from one or several abnormal parathyroid glands. Although in the vast majority of cases HPT is a sporadic disease, it can also present as a manifestation of a familial syndrome. Many benign and malignant sporadic parathyroid neoplasms are caused by loss-of-function mutations in tumor suppressor genes that were initially identified by the study of genomic DNA from patients who developed HPT as a manifestation of an inherited syndrome. Somatic and inherited mutations in certain proto-oncogenes can also result in the development of parathyroid tumors. The clinical and genetic investigation of familial HPT in kindreds found to lack germline variants in the already known HPT-predisposition genes represents a promising future direction for the discovery of novel genes relevant to parathyroid tumor development.

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“…1 In the absence of prophylactic treatment, active surveillance for early diagnosis is very important for the implementation of suitable interventions to reduce the morbidity and mortality of affected patients. 2 Most MEN1-associated tumours are multifocal and multiglandular, 3 making their diagnosis challenging. Current clinical practice guidelines recommend annual surveillance by conventional imaging tools, such as endoscopic ultrasound (EUS), magnetic resonance imaging (MRI) or computed tomography (CT).…”

Section: Introductionmentioning

confidence: 99%

“…Most MEN1‐associated tumours are multifocal and multiglandular, 3 making their diagnosis challenging. Current clinical practice guidelines recommend annual surveillance by conventional imaging tools, such as endoscopic ultrasound (EUS), magnetic resonance imaging (MRI) or computed tomography (CT).…”

Section: Introductionmentioning

confidence: 99%

The lesion detection rate of Ga‐68 DOTATATE PET/MR in multiple endocrine neoplasia type 1

Gao,

Liu,

Zhou

et al. 2024

J Med Imag Rad Onc

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IntroductionThe purpose of the study was to determine the usefulness of Ga‐68 DOTATATE PET/MR in the identification of tumours in individuals with multiple endocrine neoplasia type 1 (MEN1).MethodsIn this retrospective investigation, five individuals who had tested positive for a hereditary MEN1 variant underwent Ga‐68 DOTATATE PET/MR between May 2020 and January 2023. Several types of tumours associated with MEN1 were studied. MEN1‐related tumours included pituitary, parathyroid, gastroenteropancreatic, and adrenal. The rates of lesion identification between MRI, Ga‐68 DOTATATE PET, and Ga‐68 DOTATATE PET/MRI were examined. The maximum and mean standard uptake values (SUVmax and SUVmean) were evaluated in carefully delineated volumes of interest (VOI) for the relevant tumours.ResultsOf the 24 primary lesions, 14 were identified by Ga‐68 DOTATATE PET, 18 by MRI, and 20 by Ga‐68 DOTATATE PET/MRI. Two pituitary tumours were detected by all three techniques. All parathyroid tumours that were not detected by Ga‐68 DOTATATE PET and MRI were found by Tc‐99m MIBI SPECT/CT or/and EUS. Ga‐68 DOTATATE PET/MR detected more gastroenteropancreatic lesions. All adrenal tumours not identified by Ga‐68 DOTATATE PET were found by MRI or CT. The median SUVmax for lesions identified on Ga‐68 DOTATATE PET/MRI was 18.4 (range, 3.8‐85.2), and the median SUVmean was 12.0 (range, 2.3‐49.8).ConclusionThe combination of Ga‐68 DOTATATE PET and MRI demonstrated a higher detection rate and may be more useful in the work‐up of MEN1 providing a panoramic view of MEN1‐related lesions. To increase the identification of MEN1‐associated neuroendocrine lesions in the parathyroid gland, approaches other than Ga‐68 DOTATATE PET/MRI should be used.

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c-MET inhibition: novel treatment for sporadic and MEN1-associated GEP NETs

Cited by 5 publications

References 92 publications

Molecular Pathology of Well-Differentiated Gastro-entero-pancreatic Neuroendocrine Tumors

Molecular Pathology of Well-Differentiated Gastro-entero-pancreatic Neuroendocrine Tumors

Familial Hyperparathyroidism

The lesion detection rate of Ga‐68 DOTATATE PET/MR in multiple endocrine neoplasia type 1

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