The concept of the ‘carcinoid’: The phylogenic and ontogenic evolution of the unresolved karzinoide conundrum

Published on Jun 1, 2021in Current Opinion in Endocrine and Metabolic Research
· DOI :10.1016/J.COEMR.2021.03.009
Irvin M. Modlin81
Estimated H-index: 81
Mark Kidd66
Estimated H-index: 66
Abstract In respect of Carcinoid disease, one might well ask – why have we failed so miserably? In 1907, Oberndorfer described “karzinoide” and yet more than a century later, most diagnoses still reflect incurable metastatic disease. Attempts to address the biology and mechanistic basis of NETs have lacked logic, balanced oversight or linearity. Governance appears directed to the support of countless clinical trials, often so underpowered and scientifically improbable as to seem based more on marketing premise than medicine. Much science is devoted to the development of potentially commercial applications rather than elucidation of the mechanisms of neoplastic biology. A variety of organizations with quasi-scientific or commercial interests purport to drive research and diverse studies with no apparent focus or prioritization. Goals more often appear to seek popular acclaim and to accommodate the vogue of public debate by enthusiastic and often uninformed advocates of progress (sic) than to logically address the acquisition of information necessary to facilitate diagnosis and effect cure. Innumerable iterations of tumor nomenclature have been pondered over and discarded as if semantics might effect a cure or theological debate might inform science. Publications are often permutations and commutations of previous work and do little more than plump up personal bibliographies. Innumerable “disease observations” continue to be published, much in the mode of the reports of the early discovers of the globe-like sightings of exotic apparitions or more often, merely “me too” reflections. Treatments have been almost completely co-opted from other cancers and in the most part found to be wanting or misleading in their efficacy. Guidelines, eminence- and society-based continue to be presented with metronomic regularity and adopted by “followers”; more remindive of religious exhortations to the faithful endlessly in pursuit of Hippocratic grail. Some progress has been made – somatostatin receptor identification (40 years ago), sundry quasi-effective drugs, theranostics and receptor targeting – but unfortunately, the molecular mechanistic basis of NETs remains so inadequately defined as to obviate any intervention based upon a plausible hypothesis. There needs to be input from persons wise in science, clinical medicine and strategy development to define rational steps forward to a series of defined goals rather than an interface of marketplace and client dialogue. Short, intermediate and long-term goals need to be defined and developed rather than random excursions into the hinterland of an uncharted disease. Overall, what is obligatory for advance is the development and integration of novel technologies – molecular, mathematical, multi-analytic and genomic based – to provide the biological basis for elucidation of the disease and the development of personalized clinical management. The neuroendocrine community must move beyond the endless and relatively ineffective iterations of known knowledge and define new ways forward. Some work of noble note, may yet be done, T’is not too late to seek a newer world, but strong in will to strive, to seek, to find. Adapted from Alfred Lord Tennyson. 1842.
📖 Papers frequently viewed together
199760.39The Lancet
1 Author (JD Swales)
8 Citations
1 Author (Huda Y. Zoghbi)
16 Citations
57 Citations
#1Irvin M. Modlin (Yale University)H-Index: 81
#2Mark KiddH-Index: 66
Last. Alexandra KitzH-Index: 2
view all 17 authors...
Introduction Surgery is the only cure for neuroendocrine tumors (NETs), with R0 resection being critical for successful tumor removal. Early detection of residual disease is key for optimal management, but both imaging and current biomarkers are ineffective post-surgery. NETest, a multigene blood biomarker, identifies NETs with >90% accuracy. We hypothesized that surgery would decrease NETest levels and that elevated scores post-surgery would predict recurrence. Methods This was a multicenter ev...
4 CitationsSource
#1Lisa Bodei (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 25
#2Heiko Schöder (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 77
Last. Irvin M. Modlin (Yale University)H-Index: 81
view all 8 authors...
Peptide receptor radionuclide therapy (PRRT) is a type of radiotherapy that targets peptide receptors and is typically used for neuroendocrine tumours (NETs). Some of the key challenges in its use are the prediction of efficacy and toxicity, patient selection, and response optimisation. In this Review, we assess current knowledge on the molecular profile of NETs and the strategies and tools used to predict, monitor, and assess the toxicity of PRRT. The few mutations in tumour genes that can be e...
17 CitationsSource
#1Marianne PavelH-Index: 52
#2Kjell Öberg (Uppsala University)H-Index: 116
Last. Alfredo Berruti (University of Brescia)H-Index: 66
view all 7 authors...
99 CitationsSource
#1Kjell ÖbergH-Index: 116
#2Andrea Califano (Columbia University)H-Index: 76
Last. S. Paulson (Baylor University)H-Index: 1
view all 11 authors...
Background The lack of an accurate blood biomarker in neuroendocrine tumor (NET) disease has hindered management. The advance of genomic medicine and the development of molecular biomarkers has provided a strategy—liquid biopsy—to facilitate real-time management. We reviewed the role of a blood mRNA-based NET biomarker, the NETest, as an in vitro diagnostic (IVD). Patients and methods A systematic review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analys...
29 CitationsSource
#1Andrew M. ScottH-Index: 87
#2Ken Herrmann (UCLA: University of California, Los Angeles)H-Index: 67
Last. Irvin M. Modlin (Yale University)H-Index: 81
view all 1 authors...
Modern medicine has made extraordinary advances as various scientific technologies are applied to amplify and diversify the diagnostic and therapeutic strategies that physicians offer. Inherent in the natural enthusiasm that accompanies these developments is an exuberance and sometimes even hubris.
7 CitationsSource
#1Aman Chauhan (UK: University of Kentucky)H-Index: 13
#2Zainab FarooquiH-Index: 2
Last. Lowell B. Anthony (UK: University of Kentucky)H-Index: 3
view all 12 authors...
: Background: Neuroendocrine tumors (NETs) are rare tumors that can originate from any part of the body. Often, imaging or exploratory surgery can assist in the identification of the tumor primary site, which is critical to the management of the disease. Neuroendocrine tumors (NETs) of unknown primary constitute approximately 10-15% of all NETs. Determining the original site of the tumor is critical to providing appropriate and effective treatment. Methods: We performed a retrospective review of...
3 CitationsSource
: Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from the diffuse neuroendocrine system. They frequently originate in the gastroenteropancreatic (GEP) tract and the bronchopulmonary tree, and their incidence has steadily increased in the last 3 decades. Fundamental biologic and genomic differences underlie the clinical heterogeneity of NETs, and distinct molecular features characterize NETs of different grades and different primary sites. Although surgery remains the corners...
132 CitationsSource
The concept of neuroendocrine tumors (NETs) began in the 1900s with Oberndorfer’s description of carcinoid tumors, followed by specific cytotoxic agents and the identification of somatostatin. NETs diagnosis was confirmed by World Health Organization classification. Histopathology included immunohistochemistry with specific antibodies. Imaging was refined with molecular imaging. Somatostatin is the leading agent for controlling clinical symptoms related to hormone production. Increasing interest...
7 CitationsSource
#1Fengju Chen (BCM: Baylor College of Medicine)H-Index: 23
#2Yiqun Zhang (BCM: Baylor College of Medicine)H-Index: 31
Last. Chad J. CreightonH-Index: 91
view all 7 authors...
Purpose: The Cancer Genome Atlas data resources represent an opportunity to explore commonalities across cancer types involving multiple molecular levels, but tumor lineage and histology can represent a barrier in moving beyond differences related to cancer type. Experimental Design: On the basis of gene expression data, we classified 10,224 cancers, representing 32 major types, into 10 molecular-based “classes.” Molecular patterns representing tissue or histologic dominant effects were first re...
40 CitationsSource
#1Lisa Bodei (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 25
#2Mark KiddH-Index: 66
Last. Irvin M. Modlin (Yale University)H-Index: 81
view all 12 authors...
Background Peptide receptor radionuclide therapy (PRRT) utilizes somatostatin receptor (SSR) overexpression on neuroendocrine tumors (NET) to deliver targeted radiotherapy. Intensity of uptake at imaging is considered related to efficacy but has low sensitivity. A pretreatment strategy to determine individual PRRT response remains a key unmet need. NET transcript expression in blood integrated with tumor grade provides a PRRT predictive quotient (PPQ) which stratifies PRRT “responders” from “non...
60 CitationsSource
Cited By0