Insulin-like growth factor type 1 receptor (IGF-1R) exclusive nuclear staining: A predictive biomarker for IGF-1R monoclonal antibody (Ab) therapy in sarcomas

Asmane, Irène; Watkin, Emmanuel; Alberti, Laurent; Duc, Adeline; Marec‐Bérard, Perrine; Ray‐Coquard, Isabelle; Cassier, Philippe; Decouvelaere, Anne‐Valérie; Ranchère, Dominique; Kurtz, Jean‐Emmanuel; Bergerat, Jean‐Pierre; Blay, Jean‐Yves

doi:10.1016/j.ejca.2012.05.009

Cited by 103 publications

(81 citation statements)

References 35 publications

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“…Three of eight (37%) ES/PNET specimens were defined as positive for IGF-1R in our study. Although studies with IGF-1R antibodies in ES/PNETs are limited or disappointing, there are assertions in the literature that IGF-1R inhibitors may play a role in the treatment of ES/PNETs since it is regarded as a key mechanism in proliferation (7,12,13).…”

Section: Discussionmentioning

confidence: 99%

“…In Ewing sarcoma, the aberrant EWS/FLI-1 transcription factor product has been shown to upregulate the expression of IGF-1R (12). R1507 is an antibody directed against the human IGF-1R and the Sarcoma Alliance for Research through Collaboration conducted a phase two, multiarm study with this agent in various subtypes of recurrent or refractory sarcomas including Ewing sarcomas and concluded that IGF-1R inhibitors could play a role in the treatment of selected sarcomas (7).…”

Section: Discussionmentioning

confidence: 99%

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Insulin-like growth factor-1 receptor expression in pediatric tumors: a comparative immunohistochemical study

Karakuş¹,

Karakuş²,

Emir³

et al. 2018

Turk J Med Sci

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Background/aim: Insulin-like growth factor-1 receptor (IGF-1R) is a pivotal receptor tyrosine kinase involved in the cell cycle and malignant tumor transformation. It is differentially expressed in various types of tumors. We aimed to determine the expression of IGF-1R in different pediatric tumors and to shed light on possible new indications of anti-IGF-1R treatment approaches. Materials and methods:A total of 147 specimens were analyzed according to their expression of IGF-1R. Specimens included those from rhabdomyosarcomas, Wilms tumors, Ewing sarcoma/primitive neuroectodermal tumors, peripheral neuroblastic tumors, acute lymphoblastic lymphoma, Hodgkin lymphoma, Burkitt lymphoma, retinoblastoma, pleuropulmonary blastoma, Langerhans cell histiocytosis, endodermal sinus tumors (ESTs), and myeloid sarcoma. Analysis was performed on tissue sections by immunohistochemically staining for IGF-1R expression.Results: All six specimens of EST cases showed positivity for IGF-R1. Additionally, about 56% of the Hodgkin lymphoma, 80% of the rhabdomyosarcoma, and 70% of the Wilms tumor specimens showed positivity for IGF-R1 expression. Conclusion:All ESTs examined in our study expressed IGF-1R and to our knowledge this is the first report regarding ESTs and IGF-1R expression. IGF-1R could be included among confirmatory markers for ESTs and, from a therapeutic viewpoint, ESTs should also be examined for IGF-1R expression for beneficial regimens.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor-1 receptor expression in pediatric tumors: a comparative immunohistochemical study

Karakuş¹,

Karakuş²,

Emir³

et al. 2018

Turk J Med Sci

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“…Studies investigating the role of IGF1-1R expression, measured on tumor samples or circulating tumor cells, as biomarker for response prediction are too small to be conclusive and are not conducted in breast cancer samples (de Bono et al, 2007;Asmane et al, 2012). In BALB/c nude mice with an IGF-1R expressing human bone sarcoma xenograft, indium-111 ( 111 In)-labeled R1507 immuno-single-photon emission computed tomography was performed before treatment with R1507.…”

Section: Igf-1 -Treatment Response Predictionmentioning

confidence: 99%

Targeting breast cancer through its microenvironment: Current status of preclinical and clinical research in finding relevant targets

Nienhuis

Gaykema

Timmer‐Bosscha

et al. 2015

Pharmacology & Therapeutics

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“…A sejtosztódást szabályozó extra-és intracelluláris fe hérjék blokkolása útján ható biológiai szerekkel klinikai vizsgálatok folynak. A kizárólagosan sejtmagban elhelyezkedő IGF-1R egyszerűen vizsgálható biomarkere a sarcomáknak, amelynek célzott blokkolása (cixutumumab) metasztatikus vagy előrehaladott sarcomában hosszabb PFS-t és OS-t eredményez [35]. Fázis 2 vizsgálat során gyenge hatást mutatott, azonban a páciensek 15%-ában SD alakult ki [36].…”

Section: Célzott Kezelési Lehetőségekunclassified

A sarcoma synoviale kezelési lehetőségei

Deme¹,

Telekes

2015

Orvosi Hetilap

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A sarcoma synoviale a lágyrész-sarcomák 5-10%-ában, az összes malignus daganatok 0,05-0,1%-ában fordul elő. Főként a végtagokon keletkezik, azonban bárhol kialakulhat. A betegek 50%-ában 3-5 éven belül metasztázisok jelennek meg (tüdő, nyirokcsomó, csont), sőt akár 20 év elteltével is számítani lehet a sarcoma synoviale kiújulására. Az 5 éves teljes túlélés lokalizált betegség esetén 76%, metasztatikus esetben 10%. Az életkor, daganatméret, szö-vettani altípus és a radioterápia megtörténte befolyásolja a prognózist. Az adjuváns kemoterápia szerepe nem bizonyított. Számos klinikai vizsgálat van folyamatban a lokálisan előrehaladott, relaptálódott/refrakter és metasztatikus sarcoma synoviale kezelésére. A sarcoma synoviale biológiai viselkedésének jobb megértésével a célzott kezelés és a konvencionális terápia kombinációja válhat a jövő útjává. Orv. Hetil., 2015, 156(22), 875-880.Kulcsszavak: sarcoma synoviale, kemoterápia, radioterápia, célzott kezelés Therapeutic options for synovial sarcomaSynovial sarcomas account for approximately 5 to 10% of soft tissue sarcomas and 0.05 to 0.1% of all malignant neoplasms. They predominantly affect the extremities but can occur in any part of the body. More than 50% of the patients are expected to develop metastatic disease within 3-5 years. In some patients disease recurrence may develop after 20 years. The 5-year overall survival rate is 10% for patients with metastatic disease and 76% for patients with localized one. Age, tumour size, histological subtype, and adjuvant radiotherapy infl uence prognosis. The role of adjuvant chemotherapy has not been proven yet. There are several ongoing clinical trials to determine the effi cacy of active agents used for therapy of locally advanced, relapsed/refractory or metastatic disease. Better understanding of the biological behaviour of synovial sarcomas would provide the future way for the targeted therapy in combination with conventional treatments. Rövidítések CCND1 = ciklin D1; CR = komplett remisszió; DRFS = távoli kiújulásmentes túlélés; EFS = eseménymentes (gyógyszertoxi-citás, -intolerancia, egyéb) túlélés; EpSSG = European Pediatric Soft Tissue Sarcoma Group; HDAC = hiszton-deacetiláz; IGF-1R = inzulinszerű növekedési faktor receptor-1; KT = kemoterápia; LRFS = lokális kiújulásmentes túlélés; MD = metasztatikus betegség; MFS = áttétmentes túlélés; OS = teljes túlélés; PD = progresszív betegség; PFS = progressziómentes túlélés; PR = parciális remisszió; RT = radioterápia; SD = stabil betegség; SEER = Surveillance, Epidemiology, and End Results; SS = sarcoma synoviale A sarcoma synoviale (SS) a ritka malignitások közé tartozik. A malignus daganatok 0,05-0,1%-át és a lágyrész-sarcomák 5-10%-át alkotja [1,2]. Az SS leggyakrabban a serdülőkorúak és fi atal felnőttek 15-40 éves korosztá-lyát érinti, azonban előfordulhat 10 éven aluli gyermekekben, sőt újszülöttekben is [3]. Prognosztikai faktorokTöbb munkacsoport vizsgálta az SS-ben szenvedő pá-ciensek túlélését befolyásoló prognosztikai faktorokat, amelyek közül az 5 cm vagy ann...

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Insulin-like growth factor type 1 receptor (IGF-1R) exclusive nuclear staining: A predictive biomarker for IGF-1R monoclonal antibody (Ab) therapy in sarcomas

Cited by 103 publications

References 35 publications

Insulin-like growth factor-1 receptor expression in pediatric tumors: a comparative immunohistochemical study

Insulin-like growth factor-1 receptor expression in pediatric tumors: a comparative immunohistochemical study

Targeting breast cancer through its microenvironment: Current status of preclinical and clinical research in finding relevant targets

A sarcoma synoviale kezelési lehetőségei

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