Abstract:
:Poly (ADP-ribose) polymerase (PARP) plays a key role in DNA repair mechanisms by detecting and initiating repair after DNA strand breaks. Inhibition of PARP in DNA repair-defective tumors (like those with BRCA1 or BRCA2 mutations) can lead to gross genomic instability and cell death. Likewise, combining PARP inhibition with cytotoxic agents such as chemotherapy or radiation therapy is synergistic in many preclinical models. Several drugs designed to inhibit PARP are currently in clinical development, many following a development path different from that of typical anticancer agents. In this review we will focus on the early clinical data from PARP inhibitors that are entering clinical trials, the potential tumors they might target, their combination with other drugs and the different biomarkers that are being explored. Concepts such as 'BRCAness', synthetic lethality, Phase 0 trials and pharmacodynamic markers will be discussed in the context of the development of PARP inhibitors.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Rodon J,Iniesta MD,Papadopoulos Kdoi
10.1517/13543780802525324subject
Has Abstractpub_date
2009-01-01 00:00:00pages
31-43issue
1eissn
1354-3784issn
1744-7658journal_volume
18pub_type
杂志文章,评审abstract::Introduction: Osteoarthritis (OA) is the most common form of arthritis. Knee OA is associated with joint pain, activity limitation, physical disability, reduced health-related quality of life, and increased mortality. To date, all pharmacologic treatments for OA are directed toward pain management. Lorecivivint (LOR) ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2020.1842357
更新日期:2020-12-01 00:00:00
abstract::Neuroimmunophilin ligands are a class of compounds that hold great promise for the treatment of nerve injuries and neurological disease. In contrast to neurotrophins (e.g., nerve growth factor), these compounds readily cross the blood-brain barrier, being orally effective in a variety of animal models of ischaemia, tr...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.10.2331
更新日期:2000-10-01 00:00:00
abstract::The clinical use of cannabinoids is currently a topic of interest not exclusively, but most importantly, concerning different areas of pain therapy. One of the major obstacles in developing clinically acceptable compounds is the cannabimimetic side-effect profile of delta-9-tetrahydrocannabinol (THC) and other cannabi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780802691951
更新日期:2009-02-01 00:00:00
abstract::Restenosis, the re-narrowing of the lumen of the coronary artery, in the months following a successful percutaneous balloon angioplasty or stenting, remains the main limitation to percutaneous coronary revascularisation. Serial intravascular ultrasound studies have shown that restenosis after conventional balloon angi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.11.2555
更新日期:2000-11-01 00:00:00
abstract::A recent study has demonstrated for the first time that botulinum neurotoxin (BoNT) briefly opens tumour vessels, allowing more effective destruction of cancer cells by radiotherapy and chemotherapy. This review discusses the implications of BoNTs in cancer treatment. After briefly reviewing the different BoNT serotyp...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.2.209
更新日期:2007-02-01 00:00:00
abstract::New bolus fibrinolytic agents derived from the recombinant human tissue plasminogen activator (t-PA) have emerged as a new means of dissolution of the occlusive thrombosis associated with acute myocardial infarction. Lanoteplase is a fibrinolytic drug derived from t-PA by deleting its fibronectin finger-like and epide...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.11.2689
更新日期:2000-11-01 00:00:00
abstract:INTRODUCTION:Circadian rhythm is a natural endogenous process occurring roughly every 24 hours. Circadian rhythm dysfunction is involved in diabetic retinopathy (DR) pathogenesis. Interestingly, there are investigational drugs that exhibit potential in the treatment of DR by targeting circadian rhythm dysfunction. ARE...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2020.1842872
更新日期:2020-12-01 00:00:00
abstract::After thousands of years of interest the last few decades have seen a huge increase in our knowledge of the cannabinoids and their mode of action. Their potential as medical therapeutics has long been known. However, very real concerns over their safety and efficacy have lead to caution and suspicion when applying the...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.10.1365
更新日期:2002-10-01 00:00:00
abstract:INTRODUCTION:Asthma is a chronic inflammatory disease characterized by bronchial hyper-reactivity. Although many currently available treatment regimens are effective, poor symptom control and refractory severe disease still represent major unmet needs. In the last years, numerous molecular therapeutic targets that inte...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1212838
更新日期:2016-09-01 00:00:00
abstract::Numerous studies over the last few years have suggested that modulating the glutamatergic system may be an efficient method to achieve an antidepressant effect. Data suggest that metabotropic glutamate receptors (mGlu receptors), related to long-term, modulatory effects on glutamatergic neurotransmission, may be a goo...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.12.1545
更新日期:2006-12-01 00:00:00
abstract:INTRODUCTION:Erectile function is an important aspect in the quality of life of many men. For men with erectile dysfunction (ED), a spectrum of treatment options exists. Novel therapies for ED are currently being developed in order to delay surgical placement of a penile prosthesis - the final step in the management of...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2017.1324570
更新日期:2017-06-01 00:00:00
abstract::Celiac disease is an autoimmune condition affecting genetically susceptible individuals. It is produced by the ingestion of gluten contained in wheat, rye, barley, and related products. The only treatment currently available is strict adherence to a gluten-free diet for life. This requirement for dietary compliance is...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903369333
更新日期:2009-12-01 00:00:00
abstract::Phytoestrogens, such as the soya isoflavones genistein and daidzein, are currently being extensively investigated through both molecular, preclinical and clinical studies to determine their potential health benefits. Phytoestrogens may protect against chronic diseases such as hormone-dependent cancer (e.g., breast and...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.8.1829
更新日期:2000-08-01 00:00:00
abstract:INTRODUCTION:Recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) has a dismal prognosis. With the emergence of monoclonal antibodies and tyrosine kinase inhibitors (TKI) targeting the epidermal growth factor receptor (EGFR), several drugs were developed and tested in HNSCC. To date, the monoclonal...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1177022
更新日期:2016-06-01 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::This review focuses on the clinical development of the prototype broad spectrum inhibitor of cyclin-dependent kinases (CDKs), flavopiridol, now undergoing Phase II single-agent trials and Phase I combination trials (with paclitaxel and cisplatin). Preclinically, flavopiridol is a potent inhibitor of CDKs 1, 2 and 4 in...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.12.2903
更新日期:2000-12-01 00:00:00
abstract:INTRODUCTION:Posttraumatic stress disorder (PTSD) is a prevalent, chronic and disabling anxiety disorder that may develop following exposure to a traumatic event. There is currently no effective pharmacotherapy for PTSD and therefore the discovery of novel, evidence-based treatments is particularly important. This revi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1020109
更新日期:2015-05-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Several studies have demonstrated the high prevalence of hypertension and the crucial role of the association between endothelial function and hypertension. Thus, in depth investigation of the pathophysiological mechanisms linking endothelial dysfunction and hypertension, as well as evaluation o...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2010.522989
更新日期:2010-11-01 00:00:00
abstract:INTRODUCTION:Currently, there is no cure available for the hereditary neurodegenerative disease proximal spinal muscular atrophy (SMA), which is the number one genetic killer in early childhood. However, growing knowledge of SMA pathophysiology has opened new avenues for potential therapeutic interventions. AREAS COVE...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1038341
更新日期:2015-01-01 00:00:00
abstract::Recently there have been considerable advances made in the treatment of multiple sclerosis. For the first time since its initial clinical description in the 1800s, there are now available several medications which unequivocally exert favourable clinical effects through the lowering of the biological activity of the hu...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.4.655
更新日期:2000-04-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:The sodium/hydrogen exchanger-1 (NHE-1/SLC9A1) is a ubiquitous plasma membrane protein whose main role is maintenance of intracellular pH and volume. NHE-1 plays a role in atherogenesis; however, its clinical relevance has not yet been established. AREAS COVERED IN THIS REVIEW:We herein review ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2010.532123
更新日期:2010-12-01 00:00:00
abstract::Histone deacetylase (HDAC) inhibitors are a new class of targeted anticancer agents. Several HDAC inhibitors are in clinical trials and have shown significant activity against a spectrum of both haematological and solid tumours at doses that are well tolerated by patients. HDACs and histone acetyltransferases can, by ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.12.1497
更新日期:2005-12-01 00:00:00
abstract::Introduction: Cyclin-dependent kinase 7 (CDK7) is a part of the CDK-activating kinase family (CAK) which has a key role in the cell cycle and transcriptional regulation. Several lines of evidence suggest that CDK7 is a promising therapeutic target for cancer. CDK7 selective inhibitors such as SY-5609 and CT7001 are in...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2021.1850693
更新日期:2021-01-01 00:00:00
abstract::In spite of tremendous efforts to control cancer, the mortality associated with this disease has been increasing in developed countries in the recent decades. Inadequate efficiency of existing therapeutic regimens and the rise of multi-drug resistant cancer cells are the main factors which require a broadening of inve...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.6.1243
更新日期:2000-06-01 00:00:00
abstract::Endothelin (ET) is a pivotal physiological regulator of blood pressure through its effects on blood vessels, heart, lung and kidneys, and the ET system can be overactive in disorders such as pulmonary hypertension, heart failure and renal disease. Such observations stimulated interest among scientists and pharmaceutic...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.13.11.1419
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND:Pompholyx is a chronic relapsing inflammatory vesicobullous skin disease of the hands and feet belonging to the spectrum of eczema. Established treatments, both topical and systemic, are limited in efficacy, risk:benefit ratio and prevention of further relapses. New treatment options are needed. OBJECTIVE:T...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.6.897
更新日期:2008-06-01 00:00:00
abstract::Early breast carcinoma is defined as pathological stage 1 (pT1N0M0) tumour and its incidence has recently increased possibly due to the advent of mammography based mass screening. Overall survival of these patients is in general excellent, but more than 20% of them will eventually develop distant metastasis and die. T...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543781003718833
更新日期:2010-04-01 00:00:00
abstract:INTRODUCTION:In the last decade, concerns have been raised around the use of erythropoiesis-stimulating agents (ESAs) and intravenous iron in chronic kidney disease (CKD) patients, especially when given at high doses. Moreover, treatment with ESA is expensive. AREAS COVERED:We searched PubMed for original articles, re...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1493455
更新日期:2018-07-01 00:00:00
abstract:INTRODUCTION:Thermo transient receptor potential (thermoTRP) channels are some of the most intensely pursued therapeutic targets of the past decade. They are considered promising targets of numerous diseases including chronic pain and cancer. Modulators of these proteins, in particular TRPV1-4, TRPM8 and TRPA1, have re...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2020.1825680
更新日期:2020-11-01 00:00:00
abstract::Currently available antifungal drugs for serious infections are either fungistatic and vulnerable to resistance (azoles) or fungicidal but toxic to the host (polyenes). Cell wall-acting antifungals are inherently selective and fungicidal, features that make them particularly attractive for clinical development. Three ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.10.2.269
更新日期:2001-02-01 00:00:00