Abstract:
:The genomic characterization of acute myeloid leukemia (AML) by DNA sequencing has illuminated subclasses of the disease, with distinct driver mutations, that might be responsive to targeted therapies. Approximately 15-23% of AML genomes harbor mutations in one of two isoforms of isocitrate dehydrogenase (IDH1 or IDH2). These enzymes are constitutive mediators of basic cellular metabolism, but their mutated forms in cancer synthesize an abnormal metabolite, 2- hydroxyglutarate, that in turn acts as a competitive inhibitor of multiple gene regulatory enzymes. As a result, leukemic IDH mutations cause changes in genome structure and gene activity, culminating in an arrest of normal myeloid differentiation. These discoveries have motivated the development of a new class of selective small molecules with the ability to inhibit the mutant IDH enzymes while sparing normal cellular metabolism. These agents have shown promising anti-leukemic activity in animal models and early clinical trials, and are now entering Phase 3 study. This review will focus on the growing preclinical and clinical data evaluating IDH inhibitors for the treatment of IDH-mutated AML. These data suggest that inducing cellular differentiation is central to the mechanism of clinical efficacy for IDH inhibitors, while also mediating toxicity for patients who experience IDH Differentiation Syndrome. Ongoing trials are studying the efficacy of IDH inhibitors in combination with other AML therapies, both to evaluate potential synergistic combinations as well as to identify the appropriate place for IDH inhibitors within existing standard-of-care regimens.
journal_name
Curr Cancer Drug Targetsjournal_title
Current cancer drug targetsauthors
Becker JS,Fathi ATdoi
10.2174/1568009620666200424145622subject
Has Abstractpub_date
2020-01-01 00:00:00pages
490-500issue
7eissn
1568-0096issn
1873-5576pii
CCDT-EPUB-106094journal_volume
20pub_type
杂志文章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::Polyisoprenylated proteins (PPs) methylation by polyisoprenylated protein methyl transferase (PPMTase) is counteracted by polyisoprenylated methylated protein methyl esterase (PMPMEase). This is the only reversible step of the polyisoprenylation pathway as the relative amounts of the acid and ester forms are determine...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910791859443
更新日期:2010-09-01 00:00:00
abstract::Wild-type Wilms' tumor gene WT1 is expressed at high levels not only in most of acute myelocytic, acute lymphocytic, and chronic myelocytic leukemia, but also in various types of solid tumors including lung cancer. We tested the ability of the gene product (WT1) to serve as a target antigen for tumor specific immunot...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009023334088
更新日期:2002-03-01 00:00:00
abstract::Angiotensin II (Ang II), a main effector peptide of the renin-angiotensin system (RAS), mediates a hormonal action in the maintenance of blood pressure and electrolyte levels, and thus fluid homeostasis. Ang II also mediates paracrine, autocrine and/or intracrine actions in the control of various specific functions of...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800911795538110
更新日期:2011-05-01 00:00:00
abstract::Epithelial-mesenchymal transition (EMT) is a developmental process that converts epithelial cells into migratory and invasive cells. This process also plays an important role in cancer progression and metastasis by enabling tumor cells to leave primary sites. EMT is regulated by complex transcription networks and post...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/15680096113136660098
更新日期:2013-11-01 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::Cyclooxygenase-2 (COX-2) is a critical enzyme implicated in chronic inflammation-associated cancer development. Our studies have shown that the exposure of Beas-2B cells, a human bronchial epithelial cell line, to lung carcinogenic nickel compounds results in increased COX-2 expression. However, the signaling pathways...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800911795656001
更新日期:2011-06-01 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::One of the crucial reasons of breast cancer therapy failure is an impairment of mechanisms responsible for metabolism and cellular homeostasis, which makes it difficult to foresee the response to the treatment. Targeted therapy in breast cancer is dictated by the expression of specific molecules such as growth factor ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666171114143330
更新日期:2018-01-01 00:00:00
abstract::NUPR1 is a transcription factor that has attracted great attention because of its various roles in cancer. Several studies were carried out to determine its molecular targets and mechanism of action to develop novel therapies against cancer. Here, we shed light on the role of NUPR1 in different types of cancer. NUPR1 ...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666200703152523
更新日期:2020-01-01 00:00:00
abstract::Glioma-associated oncogenes (GLIs) are zinc finger protein family members and downstream regulatory factors of the classic Hedgehog (Hh) signaling pathway. GLI proteins influence the growth and development of organisms and aid in tissue repair. However, aberrant expression of the GLI family member GLI1 promotes carcin...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009618666171129223533
更新日期:2018-01-01 00:00:00
abstract::The efficacy of cancer immunotherapy relies on the ability of the host immune system to recognise the cancer as non-self and eliminate it from the body. Whilst this is an extremely fertile area of medical research, with positive clinical trials showing durable responses, attention must be paid to the subset of patient...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170206105131
更新日期:2018-01-01 00:00:00
abstract::The anticancer properties of histone deacetylase inhibitors have been known for some time. However, it is only recently that the functional identities of the intracellular targets mediating the anticancer properties have started to be revealed. These targets appear to play significant roles in cell cycle control, apop...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009023333818
更新日期:2002-12-01 00:00:00
abstract::Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders of hematopoietic progenitors manifest by cytopenias, bleeding, infection, and potential for progression to acute myelogenous leukemia. The wide spectrum of clinical manifestations, including variability in illness severity and potential for ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907781662284
更新日期:2007-09-01 00:00:00
abstract::UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase-6 (pp-GalNAc-T6) is a member of the N-acetyl-D-galactosamine transferase family. It catalyzes the addition of N-acetyl-D-galactosamine to proteins, often the first step in O-glycosylation of proteins. Glycosylated proteins play important role...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160922102641
更新日期:2017-01-01 00:00:00
abstract::Therapeutic vaccines continue to be one of the most active fields in cancer research. However, despite clear evidence of antitumor effect in laboratory animals, and despite the ability of current vaccine candidates to elicit tumor specific antibodies and T-cells in humans, objective responses in the clinical trials ar...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800911793743583
更新日期:2011-01-01 00:00:00
abstract::Gastrointestinal (GI) tumors are among the leading cause of death in cancer patients worldwide. Particularly, gastric cancer (GC) is the third cause of cancer deaths, whereas esophageal neoplasm is the eighth leading most common cancer worldwide and its incidence, especially adenocarcinoma type, is continuously increa...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170208162058
更新日期:2018-01-01 00:00:00
abstract::Angiogenesis is a key factor in the carcinogenesis process. In oncological practice, angiogenesis inhibition, mainly through the blockade of the VEGF family and its receptors, has been robustly demonstrated to produce clinical benefits and, in specific disease subsets such as colorectal cancer, to extend the overall s...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800912800190929
更新日期:2012-05-01 00:00:00
abstract::The actin microfilament network is important in maintaining cell shape and function in eukaryotic cells. It has a multitude of roles in cellular processes such as cell adhesion, motility, cellular signalling, intracellular trafficking and cytokinesis. Alterations in the organisation of the cytoskeleton and changes in ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800906776842948
更新日期:2006-05-01 00:00:00
abstract::Despite advances in multidisciplinary approaches, the prognosis for most patients with malignant gliomas is poor. Malignant gliomas are highly vascularized tumors with elevated expression of vascular endothelial growth factor (VEGF), an important mediator of angiogenesis. Recent studies of bevacizumab, an anti-VEGF mo...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800912799277584
更新日期:2012-03-01 00:00:00
abstract:BACKGROUND AND AIM:Translational data suggest that nucleoside transporters, in particular human equilibrative nucleoside transporter 1 (hENT1), play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of this study was to retrospectively determine patient...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800911793743600
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Current gene therapy vectors such as viral, non-viral, and bacterial vectors, which are used for cancer treatment, but there are certain safety concerns and stability issues of these conventional vectors. Exosomes are the vesicles of size 40-100 nm secreted from multivesicular bodies into the extracellular e...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666200924154149
更新日期:2020-01-01 00:00:00
abstract::Prostate cancer (CaP) is a major health problem in males in Western countries. Current therapeutic approaches are limited and many patients die of secondary disease (metastases). There is no cure for metastatic castration-resistant prostate cancer (CRPC). Targeting tumor-associated antigens is fast emerging as an area...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910791190193
更新日期:2010-05-01 00:00:00
abstract::Recent publications on the molecular characterization of malignant glioma have had profound impact on the appreciation of tumoral heterogeneity within and between patients. Both these phenomena are implicated in the variability in clinical outcome between patients, as well as the inevitable recurrence of these tumors ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160813191809
更新日期:2017-01-01 00:00:00
abstract::Heat shock protein 32 (Hsp32), also known as heme oxygenase-1 (HO-1), is a stress-related anti-apoptotic molecule, that has been implicated in enhanced survival of neoplastic cells and in drug-resistance. We here show that Hsp32 is expressed in most solid tumors and hematopoietic neoplasms and may be employed as a new...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800909789057024
更新日期:2009-08-01 00:00:00
abstract::Platinum-based chemotherapeutics are the mainstay of treatment of a range of tumors achieving high response rates but limited in the course of disease by appearance of drug resistance. Tumor cells respond with reduced uptake and increased intracellular inactivation of the drugs, as well as increased DNA repair and gen...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/15680096113136660109
更新日期:2014-01-01 00:00:00
abstract::Cisplatin is one of the most commonly used drugs in the treatment of gastric cancer. However, drug resistance is a major obstacle for effective treatment and originates in multiple mechanisms such as enhanced DNA repair and anti-apoptosis. Our previous results demonstrated that XRCC1 was a key regulator of cisplatin i...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009614666141028094612
更新日期:2015-01-01 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::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::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