Abstract:
:Various signal transduction pathways have been implicated in the pathogenesis of chronic lymphocytic leukemia (CLL), which is characterized by the progressive accumulation of monoclonal CD5+ B cells in the blood. B cell receptor (BCR) signaling appears to have a crucial role in disease onset and is thought to be induced by self or non-self-antigen recognition leading to chronic stimulation. Several of the kinases functioning downstream of the BCR are aberrantly expressed or constitutively activated in CLL. Yet, these kinases have additional roles, particularly in chemokine receptor signaling, which is essential for homing and survival of CLL cells in lymphoid organs, or in toll-like receptor signaling. Recently, small molecule inhibitors of kinases in the BCR signaling pathway have shown impressive anti-tumor activity in clinical trials. Remarkably, the observed durable responses in CLL patients were accompanied by transient increases in blood lymphocyte numbers, indicating the importance of these kinases in chemokine receptor signaling. In this review, we therefore highlight the role of BCR signaling and the important other associated signal transduction cascades for CLL cells and give an overview of novel agents that target these specific pathways and were shown to be successful for CLL treatment in clinical trials.
journal_name
Curr Cancer Drug Targetsjournal_title
Current cancer drug targetsauthors
Muggen AF,Singh SP,Hendriks RW,Langerak AWdoi
10.2174/1568009616666160408145623subject
Has Abstractpub_date
2016-01-01 00:00:00pages
669-688issue
8eissn
1568-0096issn
1873-5576pii
CCDT-EPUB-74861journal_volume
16pub_type
杂志文章,评审abstract::Actin was first identified in non-muscle cells only about three decades ago, and at about the same time, it was found that actin filaments were disrupted in the malignant transformed cells. The actin network is a rather complex, yet important structural and functional system of all eukaryotic cells. Actin filaments pr...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009043332998
更新日期:2004-06-01 00:00:00
abstract::Ovarian cancer is a leading cause of death worldwide from gynecological malignancies, mainly because there are few early symptoms and the disease is generally diagnosed at an advanced stage. In addition, despite the effectiveness of cytoreductive surgery for ovarian cancer and the high response rates to chemotherapy, ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009618666181010091246
更新日期:2019-01-01 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::Malignant brain tumors including primary brain tumors (e.g., glioblastoma multiforme) and metastases, are aggressive and lethal entities for the majority of affected patients. Current standard treatments involving combinations of surgery, radiotherapy and systemic chemotherapy offer only modest improvements in surviva...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009615666150616123548
更新日期:2015-01-01 00:00:00
abstract::MicroRNAs (miRNAs) control the expression of approximately 60% of protein-coding genes and regulate cell metabolism, proliferation, differentiation, and apoptosis. Notably, aberrant expression of miRNAs contributes to several diseases including cancer. Accumulating evidence indicates that miRNAs play important roles i...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160216130608
更新日期:2017-01-01 00:00:00
abstract::Mammalian target of rapamycin (mTOR) is a key protein kinase controlling signal transduction from various growth factors and upstream proteins to the level of mRNA translation and ribosome biogenesis, with pivotal regulatory effects on cell cycle progression, cellular proliferation and growth, autophagy and angiogenes...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910791517172
更新日期:2010-08-01 00:00:00
abstract::Head and neck cancer, the sixth most common type of cancer worldwide, is associated with a dismal prognosis that has minimally improved during the last few decades. Future advances in the treatment and prognosis of this fatal disease largely rely upon a better understanding of the molecular events that underlie tumor ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009043332736
更新日期:2004-12-01 00:00:00
abstract:BACKGROUND:Approximately one third of Diffuse Large B cell Lymphomas (DLBCL) are refractory or relapse. Novel therapeutic approaches under scrutiny include inhibitors of B-cell receptor (BCR) signaling. Protein kinase CK2 propels survival, proliferation and stress response in solid and hematologic malignancies and prom...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009617666170427110450
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Epidermal growth factor receptor (EGFR) is a well-recognised drug target exploited for treating non-small cell lung cancer (NSCLC). Gefitinib and erlotinib are first generation clinically employed inhibitors used against EGFR activating mutants. However, during course of treatment these inhibitors become ine...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170330112842
更新日期:2017-01-01 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:BACKGROUND:Oncolytic viruses (OVs), which preferentially infect cancer cells and induce host anti-tumor immune responses, have emerged as an effective melanoma therapy. Tanapoxvirus (TANV), which possesses a large genome and causes mild self-limiting disease in humans, is potentially an ideal OV candidate. Interleukin-...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009617666170630143931
更新日期:2018-01-01 00:00:00
abstract::In this early phase of the new era of molecularly targeted patient friendly cancer chemotherapy, there is a need for novel viable anticancer molecular targets. The MDM2 oncoprotein has been validated as a potential target for cancer drug development. MDM2 amplification and/or overexpression occur in a wide variety of ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009053332672
更新日期:2005-02-01 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::The greatest risk factor for the development of cervical and other cancers that have been linked to the human papillomavirus (HPV) family is the persistence of the virus. To persist for the decades required to develop HPV-related cancers, the virus must escape host immunity. HPV is a simple DNA virus that has evolved ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907780006869
更新日期:2007-02-01 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::(5Z,9Z)-11-Phenylundeca-5,9-dienoic acid was stereoselectively synthesized, based on original cross-cyclomagnesiation of 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran and buta-2,3-dien-1-ylbenzene with EtMgBr in the presence of the Cp2TiCl2 catalyst giving 2,5-dialkylydenemagnesacyclopentane in 86% yield. The acid hyd...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009615666150506093155
更新日期:2015-01-01 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::The capacity to induce new blood vessel formation or to repair damaged vessels is an attractive idea that has, for a long time, captured the attention and imagination of researchers. Beside the identification of the pro-angiogenic growth factors and their counterpart inhibitors, the discovery of endothelial progenitor...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910793358041
更新日期:2010-12-01 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::Drugs that target the vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) pathways have revolutionized the treatment of patients with metastatic renal cell cancer (RCC). Patients with clear cell RCC often have mutations or silencing of the von Hippel Lindau gene leading to an accumulati...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800908786733450
更新日期:2008-12-01 00:00:00
abstract::Inactivation of the FHIT and TP53 genes is frequently observed in primary non-small cell lung cancers (NSCLC) and cell lines and may contribute to resistance to apoptotic stimuli elicited by various anti-tumor drugs. To evaluate a possible relationship between FHIT and TP53 status and response to platinum-analogue reg...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800908785133204
更新日期:2008-08-01 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::Pokemon gene has crucial but versatile functions in cell differentiation, proliferation and tumorigenesis. It is a master regulator of the ARF-HDM2-p53 and Rb-E2F pathways. The facts that the expression of Pokemon is essential for tumor formation and many kinds of tumors over-express the Pokemon gene make it an attrac...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800910793357907
更新日期:2010-12-01 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::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::The experimental cytotoxic drug cyclopentenyl cytosine (CPEC) is an analogue of cytidine. Besides its antiviral effect, its potential use in the treatment of cancer has become an important area of research. CPEC is activated by intracellular phosphorylation ultimately forming its metabolite CPEC-TP. CPEC-TP is a non c...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907781386579
更新日期:2007-08-01 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::As microtubules are essential in many cell functions, they have been used as a target of a variety of anticancer drugs that are grouped as stabilizing (taxanes) and destabilizing (vinca-alkaloids, colchicinoids) microtubule agents. It appears clearly now that the dynamic behaviour more than modifications of microtubul...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907783220426
更新日期:2007-12-01 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