The role of imatinib mesylate (Glivec) for treatment of patients with malignant endocrine tumors positive for c-kit or PDGF-R.


:Imatinib mesylate (IM), a small molecule that is a selective inhibitor of the ABL, platelet derived growth factor receptor (PDGFR-R) and stem cell ligand receptor (c-kit) tyrosine kinases (TK). IM was also found to inhibit the TK activity of BCR/ABL fusion protein produced in chronic myelogenous leukemia, with marked clinical activity against the disease. Since both PDGF-R and c-kit both having a putative role in tumorigenesis, we investigated the efficacy and safety of the use of IM in patients with endocrine tumors unresponsive to conventional therapies that expressed c-kit and/or PDGF-R (within the framework of a comprehensive phase II multi-center study of IM in patients with solid tumors). IM was initiated at a dose of 400 mg/day, with possible dose escalation within 1 week to 600 mg/day and an option to raise the dose to 800 mg/day in the event of progression and in the absence of safety concerns for a period of up to 12 months. Between September 2002 and July 2003, 15 adult patients with disseminated endocrine tumors were recruited as follows: medullary thyroid carcinoma (MTC, n = 6); adrenocortical carcinoma (ACC, n = 4); malignant pheochromocytoma (pheo, n = 2); carcinoid (non-secreting, n = 2), neuroendocrine tumor (NET, n = 1). No objective responses were observed. MTC--disease progression in 4 patients, and treatment discontinuation in 2 patients due to adverse events; ACC--disease progression in 3 patients, and treatment discontinuation in 1 patient due to severe psychiatric adverse event; Pheo--disease progression in 2 patients; Carcinoid--stable disease in 1 patient (6.5 months), and disease progression in 1 patient; NET--disease progression in 1 patient. IM does not appear to be useful for treatment of malignant endocrine tumors, also causing significant toxicity in this patient population.


Endocr Relat Cancer


Endocrine-related cancer


Gross DJ,Munter G,Bitan M,Siegal T,Gabizon A,Weitzen R,Merimsky O,Ackerstein A,Salmon A,Sella A,Slavin S,Israel Glivec in Solid Tumors Study Group.




Has Abstract


2006-06-01 00:00:00














  • MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma.

    abstract::Type 3 deiodinase (DIO3, D3) is reactivated in human neoplasias. Increased D3 levels in papillary thyroid carcinoma (PTC) have been associated with tumor size and metastatic disease. The objective of this study is to investigate the signaling pathways involved in DIO3 upregulation in PTC. Experiments were performed in...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Romitti M,Wajner SM,Ceolin L,Ferreira CV,Ribeiro RV,Rohenkohl HC,Weber Sde S,Lopez PL,Fuziwara CS,Kimura ET,Maia AL

    更新日期:2016-03-01 00:00:00

  • Modifying impact of RET gene haplotypes on medullary thyroid carcinoma clinical course.

    abstract::The clinical course of medullary thyroid carcinoma (MTC) associated with the MEN2A syndrome as well as of sporadic MTC shows considerable heterogeneity. The disease picture varies not only between the same RET proto-oncogene mutation carriers but also among sporadic MTC patients with no RET germinal mutations, which s...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Kaczmarek-Ryś M,Ziemnicka K,Pławski A,Budny B,Michalak M,Hryhorowicz S,Hoppe-Gołębiewska J,Boruń P,Gołąb M,Czetwertyńska M,Sromek M,Szalata M,Ruchała M,Słomski R

    更新日期:2018-04-01 00:00:00

  • RET-mediated modulation of tumor microenvironment and immune response in multiple endocrine neoplasia type 2 (MEN2).

    abstract::Medullary thyroid carcinomas (MTC) arise from thyroid parafollicular, calcitonin-producing C-cells and can occur either as sporadic or as hereditary diseases in the context of familial syndromes, including multiple endocrine neoplasia 2A (MEN2A), multiple endocrine neoplasia 2B (MEN2B) and familial MTC (FMTC). In a la...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Castellone MD,Melillo RM

    更新日期:2018-02-01 00:00:00

  • M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds.

    abstract::Germline mutations in codon 918 of exon 16 of the RET gene (M918T) are classically associated with multiple endocrine neoplasia type 2B (MEN 2B) with highly aggressive medullary thyroid cancer (MTC), pheochromocytoma and a unique phenotype. The objectives of this study are to describe the rare M918V RET mutation disco...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Martins-Costa MC,Cunha LL,Lindsey SC,Camacho CP,Dotto RP,Furuzawa GK,Sousa MS,Kasamatsu TS,Kunii IS,Martins MM,Machado AL,Martins JR,Dias-da-Silva MR,Maciel RM

    更新日期:2016-12-01 00:00:00

  • Autotaxin is an inflammatory mediator and therapeutic target in thyroid cancer.

    abstract::Autotaxin is a secreted enzyme that converts extracellular lysophosphatidylcholine to lysophosphatidate (LPA). In cancers, LPA increases tumour growth, metastasis and chemoresistance by activating six G-protein coupled receptors. We examined >200 human thyroid biopsies. Autotaxin expression in metastatic deposits and ...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Benesch MG,Ko YM,Tang X,Dewald J,Lopez-Campistrous A,Zhao YY,Lai R,Curtis JM,Brindley DN,McMullen TP

    更新日期:2015-08-01 00:00:00

  • Overview of tyrosine kinase inhibitors in clinical breast cancer.

    abstract::Studies of cell models and profiling of clinical breast cancer material to reveal the mechanisms of resistance to anti-oestrogen therapy, and to tamoxifen in particular, have reported that this phenomenon can be associated with increased expression and signalling through erbB Type 1 growth factor receptors, notably th...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Agrawal A,Gutteridge E,Gee JM,Nicholson RI,Robertson JF

    更新日期:2005-07-01 00:00:00

  • HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: The state of science in medullary thyroid carcinoma: current challenges and unmet needs.

    abstract::The 16th International Multiple Endocrine Neoplasia Workshop (MEN2019) held in Houston, TX, USA, focused on emerging topics in the pathogenesis and therapy of malignant endocrine tumors associated with MEN syndromes. With MEN-2 syndromes, the most common malignancy is medullary thyroid carcinoma (MTC). In the spirit o...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Dadu R,Bagheri-Yarmand R,Ringel MD,Grubbs EG,Zafereo M,Cote G,Gagel RF,Robinson BG,Shaw KR,Hu MI

    更新日期:2020-08-01 00:00:00

  • Obestatin stimulates Akt signalling in gastric cancer cells through beta-arrestin-mediated epidermal growth factor receptor transactivation.

    abstract::Obestatin was identified as a gut peptide encoded by the ghrelin gene that interacts with the G protein-coupled receptor, GPR39. In this work, a sequential analysis of its transmembrane signalling pathway has been undertaken to characterize the intracellular mechanisms responsible for Akt activation. The results show ...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Alvarez CJ,Lodeiro M,Theodoropoulou M,Camiña JP,Casanueva FF,Pazos Y

    更新日期:2009-06-01 00:00:00

  • Identification of occult tumors by whole-specimen mapping in solitary papillary thyroid carcinoma.

    abstract::We undertook this study to estimate an accurate incidence and spread patterns of occult papillary thyroid carcinoma (PTC) in patients with a preoperative diagnosis of solitary PTC by using whole-specimen mapping of all specimens after a total thyroidectomy. Enrolled prospectively in this whole-thyroid mapping study ar...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Park SY,Jung YS,Ryu CH,Lee CY,Lee YJ,Lee EK,Kim SK,Kim TS,Kim TH,Jang J,Park D,Dong SM,Kang JG,Lee JS,Ryu J

    更新日期:2015-08-01 00:00:00

  • PRKACB variants in skeletal disease or adrenocortical hyperplasia: effects on protein kinase A.

    abstract::Genetic variants in components of the protein kinase A (PKA) enzyme have been associated with various defects and neoplasms in the context of Carney complex (CNC) and in isolated cases, such as in primary pigmented nodular adrenocortical disease (PPNAD), cortisol-producing adrenal adenomas (CPAs), and various cancers....

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Espiard S,Drougat L,Settas N,Haydar S,Bathon K,London E,Levy I,Faucz FR,Calebiro D,Bertherat J,Li D,Levine MA,Stratakis CA

    更新日期:2020-11-01 00:00:00

  • In vitro model systems to study androgen receptor signaling in prostate cancer.

    abstract::Prostate cancer (PCa) is one of the most common causes of male cancer-related death in Western nations. The cellular response to androgens is mediated via the androgen receptor (AR), a ligand-inducible transcription factor whose dysregulation plays a key role during PCa development and progression following androgen d...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Sampson N,Neuwirt H,Puhr M,Klocker H,Eder IE

    更新日期:2013-03-26 00:00:00

  • 15 YEARS OF PARAGANGLIOMA: Imaging and imaging-based treatment of pheochromocytoma and paraganglioma.

    abstract::Although anatomic imaging to assess the precise localization of pheochromocytomas/paragangliomas (PHEOs/PGLs) is unavoidable before any surgical intervention on these tumors, functional imaging is becoming an inseparable portion of the imaging algorithm for these tumors. This review article presents applications of th...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Castinetti F,Kroiss A,Kumar R,Pacak K,Taieb D

    更新日期:2015-08-01 00:00:00

  • Methylation of estrogen receptor beta promoter correlates with loss of ER-beta expression in mammary carcinoma and is an early indication marker in premalignant lesions.

    abstract::The function of estrogen receptor beta (ER-beta) in mammary tissue is not completely understood. While early observations were often conflicting, more recent data suggest an important role as a tumor-suppressor gene. A decrease of ER-beta expression has been observed in ductal carcinoma in situ and invasive carcinoma ...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Rody A,Holtrich U,Solbach C,Kourtis K,von Minckwitz G,Engels K,Kissler S,Gätje R,Karn T,Kaufmann M

    更新日期:2005-12-01 00:00:00

  • Multiple endocrine neoplasia type 1.

    abstract::Combined clinical and laboratory investigations of multiple endocrine neoplasia type 1 (MEN1) have resulted in an increased understanding of this disorder which may be inherited as an autosomal dominant condition. Defining the features of each disease manifestation in MEN1 has improved patient management and treatment...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Pannett AA,Thakker RV

    更新日期:1999-12-01 00:00:00

  • CD74 expression and its therapeutic potential in thyroid carcinoma.

    abstract::CD74, the invariant chain of major histocompatibility complex class II, is also a receptor for macrophage migration inhibitory factor (MIF). CD74 and MIF have been associated with tumor progression and metastasis in hematologic and solid tumors. In this study, we found that 60 and 65% of papillary thyroid cancers were...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Cheng SP,Liu CL,Chen MJ,Chien MN,Leung CH,Lin CH,Hsu YC,Lee JJ

    更新日期:2015-04-01 00:00:00

  • Human heterochromatin protein 1 isoform HP1beta enhances androgen receptor activity and is implicated in prostate cancer growth.

    abstract::There are currently few successful therapies for castration-resistant prostate cancer (CRPC). CRPC is thought to result from augmented activation of the androgen/androgen receptor (AR) signaling pathway, which could be enhanced by AR cofactors. In this study, heterochromatin protein 1beta (HP1beta), but not HP1alpha o...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Shiota M,Song Y,Yokomizo A,Tada Y,Kuroiwa K,Eto M,Oda Y,Inokuchi J,Uchiumi T,Fujimoto N,Seki N,Naito S

    更新日期:2010-05-18 00:00:00

  • mTOR inhibitors response and mTOR pathway in pancreatic neuroendocrine tumors.

    abstract::Medical therapy of pancreatic neuroendocrine tumors (P-NET) may take advantage of Everolimus treatment. However, the extent of therapeutic response cannot be predicted. This study was aimed to identify the possible predictive markers of response to Everolimus in P-NET. We found that Everolimus reduced the cell viabili...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Falletta S,Partelli S,Rubini C,Nann D,Doria A,Marinoni I,Polenta V,Di Pasquale C,Degli Uberti E,Perren A,Falconi M,Zatelli MC

    更新日期:2016-11-01 00:00:00

  • Inhibition of gap junction transfer sensitizes thyroid cancer cells to anoikis.

    abstract::Resistance to anoikis (matrix deprivation-induced apoptosis) is a critical component of the metastatic cascade. Molecular mechanisms underlying resistance to anoikis have not been reported in thyroid cancer cells. For an in vitro model of anoikis, we cultured follicular, papillary, and anaplastic thyroid cancer cell l...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Jensen K,Patel A,Klubo-Gwiezdzinska J,Bauer A,Vasko V

    更新日期:2011-09-20 00:00:00

  • MINDIN secretion by prostate tumors induces premetastatic changes in bone via β-catenin.

    abstract::Bone metastases are common in advanced prostate cancer patients, but mechanisms by which specific pro-metastatic skeletal niches are formed before tumor cell homing are unclear. We aimed to analyze the effects of proteins secreted by primary prostate tumors on the bone microenvironment before the settlement and propag...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Ardura JA,Álvarez-Carrión L,Gutiérrez-Rojas I,Friedman PA,Gortázar AR,Alonso V

    更新日期:2020-07-01 00:00:00

  • Management of carcinoid syndrome: a systematic review and meta-analysis.

    abstract::Carcinoid syndrome (CS) is a debilitating disease caused by functional neuroendocrine tumors. Several treatment options are available to alleviate the hormonal symptoms, but their relative efficacy is unknown. Online databases were searched for publications on the treatment of CS symptoms. Independent reviewers assess...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,meta分析


    authors: Hofland J,Herrera-Martínez AD,Zandee WT,de Herder WW

    更新日期:2019-03-01 00:00:00

  • Altered MENIN expression disrupts the MAFA differentiation pathway in insulinoma.

    abstract::The protein MENIN is the product of the multiple endocrine neoplasia type I (MEN1) gene. Altered MENIN expression is one of the few events that are clearly associated with foregut neuroendocrine tumours (NETs), classical oncogenes or tumour suppressors being not involved. One of the current challenges is to understand...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Hamze Z,Vercherat C,Bernigaud-Lacheretz A,Bazzi W,Bonnavion R,Lu J,Calender A,Pouponnot C,Bertolino P,Roche C,Stein R,Scoazec JY,Zhang CX,Cordier-Bussat M

    更新日期:2013-10-24 00:00:00

  • The natural history and treatment of non-functioning pituitary adenomas (non-functioning PitNETs).

    abstract::Non-functioning pituitary adenomas, recently alternatively termed pituitary neuroendocrine tumours (NFpitNETs), are mostly benign neoplasms that are not associated with a hormonal hypersecretory syndrome. The clinical spectrum of NFpitNETs varies from completely asymptomatic to the development of panhypopituitarism an...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Yavropoulou MP,Tsoli M,Barkas K,Kaltsas G,Grossman A

    更新日期:2020-10-01 00:00:00

  • lncRNA H19 binds VGF and promotes pNEN progression via PI3K/AKT/CREB signaling.

    abstract::Pancreatic neuroendocrine neoplasms (pNENs) are endocrine tumors arising in pancreas and is the most common neuroendocrine tumors. Mounting evidence indicates lncRNA H19 could be a determinant of tumor progression. However, the expression and mechanism of H19 and the relevant genes mediated by H19 in pNENs remain unde...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Ji M,Yao Y,Liu A,Shi L,Chen D,Tang L,Yang G,Liang X,Peng J,Shao C

    更新日期:2019-07-01 00:00:00

  • Targeted therapy for adrenocortical tumors in transgenic mice through their LH receptor by Hecate-human chorionic gonadotropin beta conjugate.

    abstract::Novel strategies are needed for the treatment of adrenocortical tumors that are usually resistant to chemotherapy. Hecate, a 23-amino acid lytic peptide, was conjugated to the 15-amino acid (81-95) fragment of the human chorionic gonadotropin beta (CGbeta) chain, which would selectively kill cancer cells expressing th...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Vuorenoja S,Rivero-Müller A,Ziecik AJ,Huhtaniemi I,Toppari J,Rahman NA

    更新日期:2008-06-01 00:00:00

  • Estrogen promotes tumor progression in a genetically defined mouse model of lung adenocarcinoma.

    abstract::Numerous epidemiological observations point to sex differences in lung cancer etiology and progression. The present study was aimed at understanding the bases of these sex differences. To test the effect of estradiol on tumor progression, we used a mouse model based on conditional Kras expression and concurrent deleti...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Hammoud Z,Tan B,Badve S,Bigsby RM

    更新日期:2008-06-01 00:00:00

  • Safety and efficacy of two starting doses of vandetanib in advanced medullary thyroid cancer.

    abstract::Vandetanib is an oral tyrosine kinase inhibitor approved for treatment of advanced symptomatic or progressive medullary thyroid cancer (MTC). The current study (Nbib1496313) evaluated the benefit-risk of two starting doses of vandetanib in patients with symptomatic or progressive MTC. Patients were randomized 1:1 to r...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,随机对照试验


    authors: Hu MI,Elisei R,Dedecjus M,Popovtzer A,Druce M,Kapiteijn E,Pacini F,Locati L,Krajewska J,Weiss R,Gagel RF

    更新日期:2019-02-01 00:00:00

  • The mechanisms and managements of hormone-therapy resistance in breast and prostate cancers.

    abstract::Breast and prostate cancer are the most well-characterized cancers of the type that have their development and growth controlled by the endocrine system. These cancers are the leading causes of cancer death in women and men, respectively, in the United States. Being hormone-dependent tumors, antihormone therapies usua...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Rau KM,Kang HY,Cha TL,Miller SA,Hung MC

    更新日期:2005-09-01 00:00:00

  • Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours.

    abstract::Neuroendocrine tumours (NET) of the gastroenteropancreatic system comprise a malignant entity with a low incidence. Only limited information is available on long-term clinical outcome and clinically applicable prognostic factors. We performed a retrospective analysis of a large, well-characterized centre-based patient...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Pape UF,Berndt U,Müller-Nordhorn J,Böhmig M,Roll S,Koch M,Willich SN,Wiedenmann B

    更新日期:2008-12-01 00:00:00

  • Role of hypoxia-inducible factor-1alpha as a cancer therapy target.

    abstract::Hypoxia occurs in solid tumours due to a mismatch between tumour growth and angiogenesis. Hypoxia in solid tumours is associated with an aggressive phenotype and resistance to radiation therapy and chemotherapy leading to poor patient prognosis. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor, which is ac...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Patiar S,Harris AL

    更新日期:2006-12-01 00:00:00

  • New drugs for medullary thyroid cancer: new promises?

    abstract::Medullary thyroid cancer (MTC) is a rare tumor arising from the calcitonin-producing parafollicular C cells of the thyroid gland, occurring either sporadically or alternatively in a hereditary form based on germline RET mutations in approximately one-third of cases. Historically, patients with advanced, metastasized M...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Spitzweg C,Morris JC,Bible KC

    更新日期:2016-06-01 00:00:00