2021
DOI: 10.3389/fonc.2020.589218
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Targeting Adrenomedullin in Oncology: A Feasible Strategy With Potential as Much More Than an Alternative Anti-Angiogenic Therapy

Abstract: The development, maintenance and metastasis of solid tumors are highly dependent on the formation of blood and lymphatic vessels from pre-existing ones through a series of processes that are respectively known as angiogenesis and lymphangiogenesis. Both are mediated by specific growth-stimulating molecules, such as the vascular endothelial growth factor (VEGF) and adrenomedullin (AM), secreted by diverse cell types which involve not only the cancerogenic ones, but also those constituting the tumor stroma (i.e.… Show more

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Cited by 22 publications
(36 citation statements)
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References 206 publications
(393 reference statements)
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“…Thus, new therapeutic alternatives are needed, and improvements are likely to come from a more thorough understanding of the molecular and cellular mechanisms governing tumor angiogenesis and the response to antiangiogenic agents. Some of these mechanisms may be triggered by molecules produced in response to increased hypoxia (e.g., HGF, SDF1a, Ang2, CXCl8, CXCl12, AM, PDGF, bFGF) which, result from excessive pruning by longer treatment duration and/ or higher doses of angiogenesis inhibitors (4,37).…”
Section: Discussionmentioning
confidence: 99%
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“…Thus, new therapeutic alternatives are needed, and improvements are likely to come from a more thorough understanding of the molecular and cellular mechanisms governing tumor angiogenesis and the response to antiangiogenic agents. Some of these mechanisms may be triggered by molecules produced in response to increased hypoxia (e.g., HGF, SDF1a, Ang2, CXCl8, CXCl12, AM, PDGF, bFGF) which, result from excessive pruning by longer treatment duration and/ or higher doses of angiogenesis inhibitors (4,37).…”
Section: Discussionmentioning
confidence: 99%
“…AM is a multifunctional peptide hormone (1) that exerts its activity through two different complex receptors formed by a G protein-coupled receptor, the calcitonin receptor-like receptor (CLR), and receptor activity modifying protein (RAMP) -2 or -3 (2,3), which confers CLR specificity for the hormone giving place to the receptors AM 1 and AM 2 , respectively. AM is widely expressed in a variety of tumor types (4,5) and was shown to be mitogenic for many human cancer cell lines in vitro (4,6) whereas several in vivo studies have also highlighted its strong contribution to neoplastic angiogenesis. Regression of tumor neo-vessels and tumor-growth inhibition were both observed upon treatment with AM-neutralizing antibodies (7)(8)(9), AM receptor (AMR) antagonist (10,11), or AMR interference (12).…”
Section: Introductionmentioning
confidence: 99%
“…The ligand for the CALCRL/RAMP1 complex is calcitonin generelated peptide (CGRP), whereas adrenomedullin (ADM) binds to CALCRL/RAMP2 and CALCRL/ RAMP3 complexes [ 51 53 ]. CGRP and ADM have multiple physiological roles, including the regulation of blood pressure [ 52 56 ]. They also contribute to various pathologic processes [ 53 , 56 ], and the key role of CGRP in migraines has led to the development and regulatory approval of inhibitory antibodies and small molecule antagonists [ 55 ].…”
Section: Genetic and Transcriptional Changes Between Diagnosis And Relapse Of Amlmentioning
confidence: 99%
“…CGRP and ADM have multiple physiological roles, including the regulation of blood pressure [ 52 56 ]. They also contribute to various pathologic processes [ 53 , 56 ], and the key role of CGRP in migraines has led to the development and regulatory approval of inhibitory antibodies and small molecule antagonists [ 55 ]. On the basis of gene expression data [ 52 , 56 60 ] and their abilities to stimulate proliferation, migration, invasiveness, and angiogenesis and to inhibit apoptosis and antitumor immune responses [ 52 , 56 , 57 , 59 65 ], CALCRL and its ligands have also been implicated in the pathogenesis of various malignant diseases.…”
Section: Genetic and Transcriptional Changes Between Diagnosis And Relapse Of Amlmentioning
confidence: 99%
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