Abstract:
INTRODUCTION:Because of the central role of the mammalian target of rapamycin (mTOR) pathway in the control and distribution of signals essential for mRNA translation of mitogenic genes and generation of oncogenic proteins, effective targeting of mTOR remains a major goal in medical oncology. AREAS COVERED:This article summarizes preclinical and clinical studies relating to the next generation of mTOR inhibitors. While rapalogs have shown activity in the treatment of breast, renal and neuroendocrine tumors, these agents do not block mTORC2, one of the two major protein complexes in which mTOR participates. In addition, there is emerging evidence that these agents only partially block mTORC1, underscoring the need for more effective mTOR inhibitors. In recent years, catalytic mTOR inhibitors have been developed, which block both mTORC1 and mTORC2. Such inhibitors show generally better activity in preclinical models than rapalogs and some of them have been or are in clinical trials in humans. EXPERT OPINION:It is anticipated that with the continuous expansion of work in this research field, the therapeutic potential of targeting the mTOR pathway for the treatment of several malignancies will reach a maximum point in the next few years and may ultimately change the way we treat several malignant tumors.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Nelson V,Altman JK,Platanias LCdoi
10.1517/13543784.2013.787066subject
Has Abstractpub_date
2013-06-01 00:00:00pages
715-22issue
6eissn
1354-3784issn
1744-7658journal_volume
22pub_type
杂志文章,评审abstract::The introduction of HIV-1 protease inhibitors in 1995 ushered in the era of highly active antiretroviral therapy. For the first time, inhibition of two key enzymes responsible for HIV replication, reverse transcriptase and protease, was possible. The combination of two nucleoside reverse transcriptase inhibitors with ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.9.1295
更新日期:2002-09-01 00:00:00
abstract:INTRODUCTION:The progression of the mammalian cell cycle is driven by the transient activation of complexes consisting of cyclins and cyclin-dependent kinases (CDKs). Loss of control over the cell cycle results in accelerated cell division and malignant transformation and can be caused by the upregulation of cyclins, t...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2011.628985
更新日期:2011-12-01 00:00:00
abstract::Presentations at the William Harvey Research Conference on PDE Inhibitors described the molecular biology, biochemical regulation. pharmacology, and therapeutic utility of inhibitors of cyclic nucleotide phosphodiesterases (PDEs). Most of the talks focused on PDE4 and PDE5. two members of the 11-member PDE family that...
journal_title:Expert opinion on investigational drugs
pub_type:
doi:10.1517/13543784.9.3.621
更新日期:2000-03-01 00:00:00
abstract:INTRODUCTION:Since the discovery of the activating V617F mutation in Janus kinase 2 (JAK2), a number of pharmacologic inhibitors of JAK2 have entered clinical trials for patients with myelofibrosis. However, ruxolitinib, approved in 2011, remains the only one currently available for treatment of myelofibrosis, with man...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2017.1323871
更新日期:2017-06-01 00:00:00
abstract:INTRODUCTION:Despite the substantial reduction in cardiovascular morbidity and mortality after the management of dyslipidemia with statins, residual risk remains even after achieving low-density lipoprotein cholesterol targets. This residual risk appears to be partly attributed to low levels of high-density lipoprotein...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2019.1582028
更新日期:2019-04-01 00:00:00
abstract:INTRODUCTION:Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast ca...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2017.1299707
更新日期:2017-04-01 00:00:00
abstract::Toll-like receptors (TLRs) form a family of pattern recognition receptors that have emerged as key mediators of innate immunity. These receptors sense invading microbes and initiate the immune response. TLR-mediated inflammation is an important pathogenic link between innate immunity and a diverse panel of clinical di...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.8.857
更新日期:2006-08-01 00:00:00
abstract::New therapies targeting critical elements of the cell cycle open novel and attractive avenues for the treatment of cancer patients. At present, the number of clinical trials that are registered with the European Organization for Research and Treatment of Cancer (EORTC) and with the US National Cancer Institute, which ...
journal_title:Expert opinion on investigational drugs
pub_type: 社论
doi:10.1517/13543784.2012.691163
更新日期:2012-08-01 00:00:00
abstract::This review highlights some important advances that have taken place in cannabinoid research over the last four years. It focuses on novel ligands that are of interest either as experimental tools or as lead compounds for therapeutic agents and possible clinical applications for some of these ligands. The molecular ta...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.7.1553
更新日期:2000-07-01 00:00:00
abstract::Suicide gene therapy is the approach whereby the genetic alteration of a cell renders it susceptible to an otherwise non-toxic prodrug. Suicide gene therapy for solid tumours has progressed rapidly since the concept was originally described: nearly all tumour types have been explored, with some, such as glioma, melano...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.8.6.777
更新日期:1999-06-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.632408
更新日期:2012-01-01 00:00:00
abstract::Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are secreted by the heart and play important roles in the compensation of congestive heart failure with their vasodilating, natriuretic, antiproliferative, lusitropic and neurohumoral-modulating properties. Based on these beneficial properties, exog...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.13.6.643
更新日期:2004-06-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.8.12.2059
更新日期:1999-12-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.3.305
更新日期:1997-03-01 00:00:00
abstract::Hepatitis C virus is the most common chronic, blood-bourne infection, affecting 170 million people worldwide, approximately 3% of the global population. Of those infected with hepatitis C virus, 50 - 85% will develop chronic hepatitis C. Although hepatitis C is primarily a disease of the liver, a diagnosis is currentl...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.4.515
更新日期:2002-04-01 00:00:00
abstract::Since the introduction of the first through the skin (TTS) therapeutic in 1980, a total of 34 TTS products have been marketed and numerous drugs have been tested by more than 50 commercial organisations for their suitability for TTS delivery. Most of the agents which have been tested have had low molecular weights, du...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.12.1887
更新日期:1997-12-01 00:00:00
abstract:INTRODUCTION:Progesterone receptor (PR) agonists (progestins) and antagonists are developed for female contraceptives. However, non-contraceptive applications of newer progestins and PR modulators are being given more attention. AREAS COVERED:The newer PR agonists including drospirenone, nomegestrol, trimegestone, die...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.642368
更新日期:2012-01-01 00:00:00
abstract:INTRODUCTION:We carried out a screen for small molecule selective inhibitors of eukaryotic DNA polymerases (pols). Dehydroaltenusin, isolated from a fungus (Alternaria tenuis), was found to be a specific inhibitor of pol α. AREAS COVERED:We succeeded in chemically synthesizing dehydroaltenusin along with five analogs....
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2011.619977
更新日期:2011-11-01 00:00:00
abstract:INTRODUCTION:Sorafenib is an oral multikinase inhibitor with anti-angiogenic and anti-proliferative activity that is indicated for use in hepatocellular and renal cell carcinomas. Sorafenib is being developed in a number of solid tumors, including breast cancer (BC). AREAS COVERED:A series of four randomized, double-b...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.689824
更新日期:2012-08-01 00:00:00
abstract:INTRODUCTION:Studies in vitro and in vivo have identified several peptides that are potentially useful in treating systemic lupus erythematosus (SLE). The rationale for their use lies in the cost-effective production, high potency, target selectivity, low toxicity, and a peculiar mechanism of action that is mainly base...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2020.1777983
更新日期:2020-08-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903376163
更新日期:2009-12-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.732065
更新日期:2012-12-01 00:00:00
abstract::Therapeutic angiogenesis has yielded promising results in animal models, including the demonstration of newly created blood vessels, increased perfusion and functional benefits. On the other hand, clinical studies using similar methods of angiogenesis have so far been disappointing. The possibility that endothelial dy...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.1.37
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:Dysregulation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is central to the pathophysiology of myeloproliferative neoplasms (MPN). Small molecule inhibitors of JAK family members are currently under investigation for the treatment of MPN. Of these, ruxolitinib ha...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2013.774373
更新日期:2013-06-01 00:00:00
abstract::While oral formulations of agonists at the serotonin (5-HT) receptor subdivisions 5-HT(1B/1D)--the "triptan" class of drugs--dominate the market for migraine therapy and while still more triptans are under development, recent research efforts have also explored other pharmacological avenues, which are mostly based on ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.12.1813
更新日期:2002-12-01 00:00:00
abstract::Major depressive disorder (MDD) affects journal_title:Expert opinion on investigational drugs pub_type: 杂志文章,评审 doi:10.1517/13543780903286396 更新日期:2009-11-01 00:00:00
abstract:INTRODUCTION:Epithelial ovarian cancer (EOC) is the leading cause of gynaecologic cancer death. Although in some cases initial treatment is effective, most of the women diagnosed with EOC will probably need medical treatment for their disease. There is a critical need to develop effective new strategies for the managem...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2013.816282
更新日期:2013-10-01 00:00:00
abstract::Introduction: Molecular analyzes including molecular descriptor/phenotype interactions have led to better characterization of epithelial ovarian cancer patients, including a definition of a BRCA wild-type (BRCAwt) phenotype. Understanding how and when to use agents targeted against dependent BRCAwt pathways or other m...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2019.1657403
更新日期:2019-09-01 00:00:00
abstract::Considerable advances have been made on compounds that are active as inhibitors of HIV entry and fusion. The discovery of chemokines a few years ago focused the attention on coreceptor inhibitors in addition to fusion and attachment blockers. During the last 5 years, there has been an intense research activity from bo...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.1.11
更新日期:2007-01-01 00:00:00
abstract::Transcription factors are proteins that regulate gene transcription and expression. In many cases of acute leukaemia chromosomal aberrations are translocations of transcription factors which change their expression and induce the leukaemic phenotype. These abnormal transcription factors are tumour-specific and can be ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.2.329
更新日期:2000-02-01 00:00:00