Abstract:
:Although the imatinib based therapy of chronic myeloid leukemia (CML) represents a triumph of medicine, not all patients with CML benefit from this drug due to the development of resistance and intolerance. The interruption of imatinib treatment is often followed by clinical relapse, suggesting a failure in the killing of residual leukaemic stem cells. There is need to identify alternative selective molecular targets for this disease and develop more effective therapeutic approaches. Alternative pre-mRNA splicing (AS) is an epigenetic process that greatly diversifies the repertoire of the transcriptome. AS orchestrates interactions between various types of proteins and between proteins and nucleic acids. Changes caused by individual splicing events in the cells are small, however, "splicing programs" typically react to these individual changes with considerable effects in cell proliferation, cell survival, and apoptosis. Current evidence suggests a pivotal role of AS in leukemias, particularly in myelodisplastic syndrome (MDS) and chronic lymphocyte leukemia (CLL). From these studies and studies in other malignances, it is clear that splicing abnormalities play a significant role in malignant transformation. Evaluation of AS events in CML can be used to identify novel disease markers and drugsensitive targets to overcome the limits of the small molecule inhibitors currently used for treating patients with CML. The use of aberrant splice variants as disease markers has been reported, however, little is known about the use of splicing abnormalities as drug targets in CML. Herein we discuss potential therapeutic approaches that can be used to target splicing abnormalities in CML.
journal_name
Curr Cancer Drug Targetsjournal_title
Current cancer drug targetsauthors
Adamia S,Pilarski PM,Bar-Natan M,Stone RM,Griffin JDdoi
10.2174/15680096113139990083subject
Has Abstractpub_date
2013-09-01 00:00:00pages
735-48issue
7eissn
1568-0096issn
1873-5576pii
CCDT-EPUB-54715journal_volume
13pub_type
杂志文章,评审abstract::Prostate cancer is the most frequently diagnosed tumor in industrialized countries. Endocrine therapy, which is based on interference with androgen signaling is only palliative. Drugs used in prostate cancer therapy are luteinizing hormone releasing hormone (LHRH) agonists and antiandrogens. Application of LHRH agonis...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009043332925
更新日期:2004-08-01 00:00:00
abstract::Degradation of extracellular matrix is crucial for malignant tumor growth, invasion, metastasis and angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all matrix components. Elevated levels of distinct MMPs can be detected ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009053765799
更新日期:2005-05-01 00:00:00
abstract::Prevention is one of the most important and promising strategies to control cancer. Many dietary bioactive compounds, mostly phytochemicals, have been found to decrease the risk of carcinogenesis. Modulating the metabolism and disposition pathways of carcinogens represents one of the major mechanisms by which dietary ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907781386669
更新日期:2007-08-01 00:00:00
abstract::Membrane ion channels participate in cancerous processes such as proliferation, migration and invasion, which contribute to metastasis. Increasing evidence indicates that voltage-dependent K(+) (Kv) channels are involved in the proliferation of many types of cells, including tumor cells. Kv channels have generated imm...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800909790192400
更新日期:2009-12-01 00:00:00
abstract::The peptidyl prolyl isomerase (Pin1) that induces cis-trans isomerization of the peptide bond involving serine/threonine-proline has recently been shown to regulate the activity of many phosphoproteins including the ones involved in damage response pathways. We investigated Pin1 as a potential target for enhancing the...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800911794519761
更新日期:2011-03-01 00:00:00
abstract::Breast cancer is one of the most common malignancies among women, representing nearly 30% of newly diagnosed cancers every year. Till date, various therapeutic interventions, including surgery, chemotherapy, hormonal therapy, and radiotherapy are available and are known to cause a significant decline in the overall mo...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009615666141229152256
更新日期:2015-01-01 00:00:00
abstract::Following the discovery that defective retinoid signaling directly contributes to tumorigenesis, and, that retinoids have an anti-cancer effect in vitro and in vivo, retinoids have become part of the routine care in children with neuroblastoma at the stage of minimal residual disease. However, many patients still rela...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800911796798968
更新日期:2011-09-01 00:00:00
abstract::Coordination between the amplification of the fibroblast growth factor FGF19, overexpression of its corresponding receptor FGFR4, and hyperactivation of the downstream transmembrane enzyme β-klotho has been found to play pivotal roles in mediating tumor development and progression. Aberrant FGF19-FGFR4 signaling has b...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009618666180319091731
更新日期:2019-01-01 00:00:00
abstract::Sporadic colorectal cancer develops through a number of functional mutations. Key events are mutually exclusive mutations in BRAF or RAS oncogenes. Signatures for BRAF oncogene have been revealed in melanoma. In a previous study we have reported a molecular signature for HRAS and KRAS mutations in colorectal cell line...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800912802429364
更新日期:2012-09-01 00:00:00
abstract::Targets for cancer therapy are conventionally selected by identification of molecules acting downstream of established tumour suppressors and oncoproteins, such as p53, c-Myc and Ras. However, the forward genetics approach provides an alternative, conceptually distinct, strategy for identifying target molecules de nov...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Osteosarcoma is an aggressive bone tumor. Itrepresents the principal cause of cancer-associated death in children.Considering the recent findings on the role of iron in cancer, iron chelation has been investigated for its antineoplastic properties in many tumors. Deferasirox is the most used iron chelator co...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666201230090531
更新日期:2020-12-29 00:00:00
abstract::Heat shock proteins (HSPs) are molecular chaperones that stabilize folding and conformation of normal as well as oncogenic proteins. These chaperones thereby prevent the formation of protein aggregates. HSPs are often overexpressed in human malignancies, including AML. HSP90 is the main chaperon required for the stabi...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909789271486
更新日期:2009-09-01 00:00:00
abstract::One of the challenges of cancer therapeutics is to discover targets unique to the tumor cell population. Constitutively activated tyrosine kinases play a role in the malignant phenotype in a number of different cancers. While the kinases may be present in the normal cell, the cancer cell is often dependent upon the ac...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800906779010209
更新日期:2006-12-01 00:00:00
abstract:BACKGROUND:MicroRNA (miRNA) therapy, which was widely considered to treat a series of cancer, has been confronted with numerous obstacles to being delivered into target cells because of its easy biodegradation and instability. METHODS:In this research, we successfully constructed 11-mercaptoundecanoic acid modified go...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009618666181016144855
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Improving poorly soluble drugs into druggability was a major problem faced by pharmaceutists. Nanosuspension can improve the druggability of insoluble drugs by improving the solubility, chemical stability and reducing the use of additives, which provided a new approach for the development and application of ...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009618666180629150927
更新日期:2019-01-01 00:00:00
abstract::Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the Philadelphia-positive chromosome deriving from a translocation between chromosomes 22 and 9. The oncogenic product of this aberrant chromosome is the constitutively active tyrosine kinase BCR-ABL that is responsible for leukemic cell growth,...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800912800673239
更新日期:2012-06-01 00:00:00
abstract::Amplification of the HER-2 gene occurs in approximately 25% of breast cancers, causing up-regulation of key signaling pathways which control cell growth and survival. In breast cancer patients, HER-2 overexpression correlates with an aggressive phenotype and poor prognosis. HER-2, therefore, has become the focus of ma...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909788166484
更新日期:2009-05-01 00:00:00
abstract::Hepatocellular carcinoma (HCC), considered to be one of the most lethal cancers with almost > 1 million deaths reported annually worldwide, remains a devastating disease with no known effective cure. Hence, chemopreventive strategies come into play, offering an effective and safe mode of treatment, ideal to ward off p...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800912803987968
更新日期:2012-11-01 00:00:00
abstract:BACKGROUND:Cathepsin D (CATD), one of the aspartyl endoproteinase involved in different physiological processes and signaling pathways, is accountable for metabolic breakdown of intracellular proteins, the activation of growth factors, hormones, and precursors of enzyme, the processing of antigens, enzyme inhibitors an...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666161229145115
更新日期:2017-01-01 00:00:00
abstract::Exosomes are small vesicles that are secreted by various types of cells, known to mediate signal transduction between cells. During recent years, novel carriers for the delivery of targeted drugs, chemotherapy drugs and RNAs are under development, which is believed to be beneficial for patients. Considering issues of ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170710120311
更新日期:2018-01-01 00:00:00
abstract::Cancer is a disease in which cellular growth regulatory networks are disrupted. Lesions in well-characterized oncogenes and tumor suppressors often contribute to the dysregulation, but recent work has also uncovered the fundamental importance of enzymes that modulate the acetylation status of chromatin to the initiati...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009033481994
更新日期:2003-06-01 00:00:00
abstract::Aurora kinases and cyclin-dependent kinases, which play critical roles in the cell cycle and are frequently overexpressed in a variety of tumors, have been suggested as attractive targets for cancer therapy. JNJ-7706621, a recently identified dual inhibitor of these kinases, is reported to induce cell cycle arrest, en...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800912801784839
更新日期:2012-07-01 00:00:00
abstract::The histone deacetylase inhibitors are a new class of cytostatic agents that inhibit the proliferation of tumor cells in culture and in vivo by inducing cell cycle arrest, differentiation and/or apoptosis. Histone acetylation and deacetylation play important roles in the modulation of chromatin topology and the regula...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009043481560
更新日期:2004-03-01 00:00:00
abstract::Selection of treatment options for clinically localized prostate cancer is based on a host of factors including the patient's age, overall health status, potential complications, clinical tumor stage and Gleason score. It is widely acknowledged that androgen independent disease remains the main obstacle to improving t...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009043481623
更新日期:2004-02-01 00:00:00
abstract::The ubiquitin system controls protein stability and function. F-box proteins form SCF (SKP1-Cullin1-F-box protein)-type ubiquitin (E3) ligases to selectively target their substrates for degradation via the ubiquitin-proteasome pathway. Here, we review F-box proteins associated with cancer development. S-phase kinase-a...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666151112122231
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:CYP1B1 is recognized as a valuable target for chemotherapy. It catalyzes the bioactivation of naphthoquinone oximes within certain cancer cell lines. However, the expression level of CYP1B1 in melanoma and the functional role regulating the activity of DMAKO-20 as a representative naphthoquinone oxime agains...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666201116112937
更新日期:2020-11-15 00:00:00
abstract::The resistance of tumors to a number of structurally and functionally unrelated chemotherapeutic drugs has been a major obstacle for successful cancer chemotherapy. An important mechanism leading to multidrug resistance (MDR) is the overexpression of the 170 kDa P-glycoprotein (P-gp), which is a member of the ATP-bind...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/15680096113139990082
更新日期:2013-10-01 00:00:00
abstract::Human mesenchymal stem cells (hMSCs) consist of cells that can differentiate into mesenchymal tissues, including osteoblasts, adipocytes and chondrocytes. hMSCs constitute a particular stem cell niche in the stromal compartment of the bone marrow, and also play a role in maintaining the normal function of haematopoiet...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910791208553
更新日期:2010-06-01 00:00:00
abstract::The potential clinical applications of the prototype first-in-class Hsp90 inhibitor 17AAG and other emerging Hsp90 drugs are very exciting. Rigorously planned and executed clinical trials, incorporating measurement of appropriate biomarkers and pharmocodynamic endpoints are critical for selecting the optimal dose and ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009033481813
更新日期:2003-10-01 00:00:00
abstract::Several subtypes of T cells are located in a tumor environment, each of which supplies their energy using different metabolic mechanisms. Since the cancer cells require high levels of glucose, the conditions of food poverty in the tumor environment can cause inactivation of immune cells, especially the T-effector cell...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666200720010647
更新日期:2020-01-01 00:00:00