Abstract:
:Chemotherapy remains the major treatment option for castration-resistant prostate cancer (CRPC) and limited cytotoxic options are available. Inherent chemotherapy resistance occurs in half of all patients and inevitably develops even in those who initially respond. Docetaxel has been the mainstay of therapy for 6 years, providing a small survival benefit at the cost of significant toxicity. Cabazitaxel is a promising second-line agent; however, it is no less toxic, whereas mitoxantrone provides only symptomatic benefit. Multiple cellular pathways involving apoptosis, inflammation, angiogenesis, signalling intermediaries, drug efflux pumps and tubulin are implicated in the development of chemoresistance. A thorough understanding of these pathways is needed to identify biomarkers that predict chemotherapy resistance with the aim to avoid unwarranted toxicities in patients who will not benefit from treatment. Until recently, the search for predictive biomarkers has been disappointing; however, the recent discovery of macrophage inhibitory cytokine 1 as a marker of chemoresistance may herald a new era of biomarker discovery in CRPC. Understanding the interface between this complex array of chemoresistance pathways rather than their study in isolation will be required to effectively predict response and target the late stages of advanced disease. The pre-clinical evidence for these resistance pathways and their progress through clinical trials as therapeutic targets is reviewed in this study.
journal_name
Endocr Relat Cancerjournal_title
Endocrine-related cancerauthors
Mahon KL,Henshall SM,Sutherland RL,Horvath LGdoi
10.1530/ERC-10-0343subject
Has Abstractpub_date
2011-07-04 00:00:00pages
R103-23issue
4eissn
1351-0088issn
1479-6821pii
ERC-10-0343journal_volume
18pub_type
杂志文章,评审abstract::The androgen receptor (AR) signaling axis drives all stages of prostate cancer, including the lethal, drug-resistant form of the disease termed castration-resistant prostate cancer (CRPC), which arises after failure of androgen deprivation therapy (ADT). Persistent AR activity in spite of ADT and the second-generation...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-16-0422
更新日期:2016-12-01 00:00:00
abstract::Metastatic duodenopancreatic neuro-endocrine tumors (dpNETs) are the most important disease-related cause of death in patients with multiple endocrine neoplasia type 1 (MEN1). Nonfunctioning pNETs (NF-pNETs) are highly prevalent in MEN1 and clinically heterogeneous. Therefore, management is controversial. Data on prog...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-19-0372
更新日期:2020-06-01 00:00:00
abstract::PD-L1 expression is being considered a potential biomarker for response of anti-PD-1 or anti-PD-L1 agents in various tumors. The reported frequency of PD-L1 positivity varies in thyroid carcinomas, and multiple factors may contribute to the variability in PD-L1 positivity. We evaluated the PD-L1 expression in various ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-16-0421
更新日期:2017-02-01 00:00:00
abstract::There is a trend of increasing prevalence of neuroendocrine tumors (NETs), and the inherited multiple endocrine neoplasia type 1 (MEN1) syndrome serves as a genetic model to investigate how NETs develop and the underlying mechanisms. Menin, encoded by the MEN1 gene, at least partly acts as a scaffold protein by intera...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-17-0298
更新日期:2017-10-01 00:00:00
abstract::The leucine-rich repeats and immunoglobulin-like domains (LRIG) family of transmembrane proteins contains three vertebrate members (LRIG1, LRIG2 and LRIG3) and one member each in flies (Lambik) and worms (Sma-10). LRIGs have stepped into the spotlight as essential regulators of growth factor receptors, including recep...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-14-0179
更新日期:2014-01-01 00:00:00
abstract::Paragangliomas (PGLs) have widely different metastastic potentials. Two different types of PGLs can be defined by expression profiling. Cluster 1 PGLs exhibit VHL and/or succinate dehydrogenase (SDH) mutations and a pseudohypoxic phenotype. RET and neurofibromatosis type 1 (NF1) mutations occur in cluster 2 tumors cha...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-10-0184
更新日期:2011-04-28 00:00:00
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
doi:10.1530/ERC-20-0309
更新日期:2020-11-01 00:00:00
abstract::Malignant growth of small-cell lung carcinoma is promoted by various neuroendocrine autocrine/paracrine loops. Therefore, to interfere with this mitogenic process, it is crucial to elucidate the mechanisms involved. It is known that the oxytocin (OT) and vasopressin (VP) genes, normally transcriptionally restricted in...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.00803
更新日期:2004-12-01 00:00:00
abstract::Colony-stimulating factor 1 (CSF1) is a key regulator of mammary gland development, and a modulator of tissue macrophages. Expression of the CSF1 receptor gene C-FMS (CSF1R) is strongly associated with poor outcome in breast cancer and results in tumor cell invasiveness and pro-metastatic behavior in vitro. However, C...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-13-0198
更新日期:2013-10-14 00:00:00
abstract::Prostate cancer is the most common cancer in men, resulting in over 10 000 deaths/year in the UK. Sequencing and copy number analysis of primary tumours has revealed heterogeneity within tumours and an absence of recurrent founder mutations, consistent with non-genetic disease initiating events. Using methylation prof...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-14-0454
更新日期:2015-04-01 00:00:00
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
doi:10.1530/ERC-14-0269
更新日期:2015-04-01 00:00:00
abstract::The imprinted gene, neuronatin (NNAT), is one of the most abundant transcripts in the pituitary and is thought to be involved in the development and maturation of this gland. In a recent whole-genome approach, exploiting a pituitary tumour cell line, we identified hypermethylation associated loss of NNAT. In this repo...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-09-0008
更新日期:2009-06-01 00:00:00
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
doi:10.1677/erc.0.0060449
更新日期:1999-12-01 00:00:00
abstract::Thyroid cancer is on the rise. Novel approaches are needed to improve the outcome of patients with recurrent and advanced metastatic thyroid cancers. FDA approval of suberoylanilide hydroxamic acid (SAHA; vorinostat), an inhibitor of histone deacetylase, for the treatment of hematological malignancies led to the clini...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-16-0103
更新日期:2016-07-01 00:00:00
abstract::Cancer cells often display chromosomal instability (CIN), a defect that involves loss or rearrangement of the cell's genetic material - chromosomes - during cell division. This process results in the generation of aneuploidy, a deviation from the haploid number of chromosomes, and structural alterations of chromosomes...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-17-0187
更新日期:2017-09-01 00:00:00
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
doi:10.1530/ERC-15-0152
更新日期:2015-08-01 00:00:00
abstract::Ten to fifteen percent of fine-needle aspiration biopsy (FNAB) of thyroid nodules are indeterminate. Galectin-3 (Gal-3) and the oncogene BRAFV600E are markers of malignancy useful to improve FNAB accuracy. The objective of this study was to determine whether the combined analysis of Gal-3 and BRAFV600E expression in t...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-07-0147
更新日期:2007-12-01 00:00:00
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
doi:10.1530/ERC-17-0452
更新日期:2018-04-01 00:00:00
abstract::The fight against cancer has seen major breakthroughs in recent years. More than a decade ago, tyrosine kinase inhibitors targeting constitutively activated signaling cascades within the tumor inaugurated a new era of oncological therapy. Recently, immunotherapy with immune checkpoint inhibitors has started to revolut...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-16-0169
更新日期:2016-10-01 00:00:00
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
doi:10.1530/ERC-15-0162
更新日期:2016-03-01 00:00:00
abstract::Prostate cancer development and progression is largely dependent on androgen receptor (AR) signaling. AR is a hormone-dependent transcription factor, which binds to thousands of sites throughout the human genome to regulate expression of directly responsive genes, including pro-survival genes that enable tumor cells t...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-19-0181
更新日期:2020-02-01 00:00:00
abstract::The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is a key signaling pathway that has been linked to both tumorigenesis and resistance to therapy in prostate cancer and other solid tumors. Given the significance of the PI3K/Akt/mTOR pathway in integrating cell survival signals a...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-12-0394
更新日期:2013-05-20 00:00:00
abstract::Cancers of the reproductive tract account for 12% of all malignancies in women. As previous studies have shown that oestrogen metabolites can cause apoptosis, we characterised the effect of oestrogen and oestrogen metabolites on non-cancerous and cancerous human endometrial cells. Herein, we demonstrate that 2-methoxy...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-07-0008
更新日期:2007-06-01 00:00:00
abstract::Forty years ago, physicians caring for the J-kindred, a 100+ member family with multiple endocrine neoplasia type 2A (MEN2A), hypothesized that early thyroidectomy based on measurement of the biomarker calcitonin could cure patients at risk for development of medullary thyroid carcinoma (MTC). We re-evaluated 22 famil...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-20-0108
更新日期:2020-08-01 00:00:00
abstract::The high degree of conservation in microRNA from Caenorhabditiselegans to humans has enabled relatively rapid implementation of findings in model systems to the clinic. The convergence of the capacity for genomic screening being implemented in the prevailing precision medicine initiative and the capabilities of microR...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-16-0525
更新日期:2017-05-01 00:00:00
abstract::Thyrotoxicosis with concomitant thyroid cancer is rare and poorly recognized, which may result in delayed diagnosis, inappropriate treatment and even poor prognosis. To provide a comprehensive guidance for clinicians, the etiology, pathogenesis, diagnosis and treatment of this challenging setting were systematically r...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-19-0129
更新日期:2019-07-01 00:00:00
abstract::Pituitary tumor-transforming gene 1-binding factor (PTTG1IP; PBF) is a multifunctional glycoprotein, which is overexpressed in a wide range of tumours, and significantly associated with poorer oncological outcomes, such as early tumour recurrence, distant metastasis, extramural vascular invasion and decreased disease-...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-16-0340
更新日期:2017-09-01 00:00:00
abstract::To analyze the genetic alterations of pheochromocytomas and evaluate the difference among malignant, extra-adrenal, and benign pheochromocytomas. Forty-three tumor samples were tested for genetic changes using multiplex ligation-dependent probe amplification. Among them, 39 samples were available for protein expressio...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-07-0188
更新日期:2008-03-01 00:00:00
abstract::FOXE1 is a thyroid-specific transcription factor essential for thyroid gland development and maintenance of the differentiated state. Interestingly, a strong association has been recently described between FOXE1 expression and susceptibility to thyroid cancer, but little is known about the mechanisms underlying FOXE1-...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-19-0156
更新日期:2020-03-01 00:00:00
abstract::Deubiquitinases (DUBs) play important roles and therefore are potential drug targets in various diseases including cancer and neurodegeneration. In this review, we recapitulate structure-function studies of the most studied DUBs including USP7, USP22, CYLD, UCHL1, BAP1, A20, as well as ataxin 3 and connect them to reg...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-14-0516
更新日期:2015-02-01 00:00:00