Abstract:
:Introduction: Advanced melanoma historically had a very poor outcome but targeted therapies and immune checkpoint inhibitors (IC) have changed the course of the disease and made durable responses possible. However, most patients will develop progressive disease, so further strategies to overcome treatment resistance are needed. Areas covered: Current treatment strategies and landmark trials are discussed. Novel targeted agents, immune checkpoint inhibitors, and further immune-modulatory drugs, cancer vaccines and tumor infiltrating lymphocytes and their potential role in the treatment of melanoma are described. Current trials investigating these emerging agents and treatment strategies were searched for on ClinicalTrials.gov and are presented on the background of the current literature explaining the rationale for employing these new agents and strategies. Combinations of tumor-directed agents with those causing immune augmentation as well as a new adjuvant and neoadjuvant strategies are discussed. Expert opinion: Questions regarding treatment combination, personalization, and sequence of treatment will become increasingly important and will be guided by new biomarkers. New treatment settings will broaden the patient selection and will highlight the need for further discussions regarding toxicity in long-term survivorship.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Boos LA,Leslie I,Larkin Jdoi
10.1080/13543784.2020.1769066subject
Has Abstractpub_date
2020-07-01 00:00:00pages
739-753issue
7eissn
1354-3784issn
1744-7658journal_volume
29pub_type
杂志文章,评审abstract:INTRODUCTION:Sepsis with Bacillus anthracis infection has a very high mortality rate despite appropriate antibiotic and supportive therapies. Over the past 15 years, recent outbreaks in the US and in Europe, coupled with anthrax's bioterrorism weapon potential, have stimulated efforts to develop adjunctive therapies to...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1041587
更新日期:2015-01-01 00:00:00
abstract::COPD is a chronic disease of the lung that is characterised by decreased air flow and associated abnormal inflammatory responses of the lungs. A total of 80% of COPD incidences are observed in patients with history of smoking tobacco. The chronic condition of COPD is characterised by airway remodelling, which leads to...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.7.1069
更新日期:2007-07-01 00:00:00
abstract:INTRODUCTION:Aberrant regulation of platelet-derived growth factors (PDGFs) and their receptors (PDGFR) has been shown to be involved in many solid tumors, including breast cancer. PDGFR-α and PDGFR-β expressions were documented in breast cancer and are correlated with tumor aggressiveness and metastasis. Preclinical e...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.895323
更新日期:2014-05-01 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::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::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 inhibitio...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780802525324
更新日期:2009-01-01 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
abstract:BACKGROUND:Despite exciting progress and growth in the understanding of molecular and cellular mechanisms of chronic pain, osteoarthritis (OA) pain remains a challenging clinical entity to treat. There is an emerging diversity of algogenic mechanisms suggesting heterogeneity in pain aetiology in the OA patient populati...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.5.619
更新日期:2008-05-01 00:00:00
abstract:INTRODUCTION:Patients with myelofibrosis (MF) have no effective treatment option after the failure of approved JAK inhibitor (JAKi) therapy. Non-JAK inhibitors (non-JAKi) that target non-canonical molecular pathways are undergoing clinical evaluations to optimize efficacy and/or to reduce hematological toxicity of JAKi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2020.1751121
更新日期:2020-05-01 00:00:00
abstract::A major session at this annual gathering of the cancer researchers from around the globe dealt with the current state of immunotherapy for cancer. Immunotherapy is a form of cancer treatment that enhances its scientific promise and legitimacy with each passing year. As a result, this topic has become one of the most h...
journal_title:Expert opinion on investigational drugs
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doi:10.1517/13543784.9.6.1413
更新日期:2000-06-01 00:00:00
abstract::Therapeutic angiogenesis is a novel approach to the treatment of ischaemic or occlusive coronary and peripheral vascular disease. The therapeutic concept is based on the restoration of distal blood flow by the enlargement of existing vessels and tissue perfusion by the induction of new capillaries. Initial studies hav...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.13.10.1319
更新日期:2004-10-01 00:00:00
abstract:INTRODUCTION:Axial spondyloarthritis (AxS pA) is a chronic inflammatory disease for which, until recently, there were no valid therapeutic alternatives to TNF-α blocking agents. This unmet clinical need led to explore several therapeutic targets, from proinflammatory cytokines to intracellular signaling systems. The re...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2017.1337744
更新日期:2017-07-01 00:00:00
abstract:INTRODUCTION:Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Pharmacological treatment of AD includes Anticholinesterase Inhibitors (AChEIs) for mild-moderate AD, and memantine for severe AD. These drugs provide mainly symptomatic short-term benefits without clearly influencing the progres...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2017.1265504
更新日期:2017-01-01 00:00:00
abstract:INTRODUCTION:Heat shock protein 90 (HSP90) serves as a critical facilitator for oncogene addiction. There has been augmenting enthusiasm in pursuing HSP90 as an anticancer strategy. In fact, since the initial serendipitous discovery that geldanamycin (GM) inhibits HSP90, the field has rapidly moved from proof-of-concep...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.902442
更新日期:2014-05-01 00:00:00
abstract::TNP-470, an analogue of fumagillin, has been shown to inhibit angiogenesis in vitro and in vivo. In 1992, TNP-470 entered clinical development for cancer as an anti-angiogenic agent. It is currently in Phase I/II trials in Kaposi's sarcoma, renal cell carcinoma, brain cancer, breast cancer, cervical cancer and prostat...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.6.1383
更新日期:2000-06-01 00:00:00
abstract::Heat shock proteins are vital to cell survival under conditions of stress. They bind client proteins to assist in protein stabilization, translocation of polypeptides across cell membranes and recovery of proteins from aggregates. Heat shock protein inhibitors are a diverse group of novel agents that have been demonst...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903158934
更新日期:2009-09-01 00:00:00
abstract::The association of abnormalities in the cellular and humoral immune system with various autoimmune diseases provides the rationale for apheresis technologies. While plasmapheresis or plasma exchange is limited by its non-selective removal of all plasma components, modern apheresis techniques aim to provide more specif...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.9.2017
更新日期:2000-09-01 00:00:00
abstract:INTRODUCTION:The prognosis for patients with oesophagogastric (OG) cancer remains poor, with a median survival of approximately 9 - 11 months for patients with metastatic disease. However, a more personalised approach to treatment, using drugs tailored to the molecular characteristics of patients' tumours, has the pote...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.930126
更新日期:2014-10-01 00:00:00
abstract::AGI-1067 is a derivative of probucol that is a promising new development for the treatment of restenosis and possibly atherosclerosis. In monkeys fed a high-fat diet for 1 year, AGI-1067 prevented the development of atherosclerosis. In these monkeys, AGI-1067 lowered plasma levels of low-density lipoprotein (LDL)-chol...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.11.1855
更新日期:2003-11-01 00:00:00
abstract:BACKGROUND:Polidocanol is a liquid surfactant having endothelial cell lytic properties. In the form of a controlled, dispensed microfoam it is administered endovenously as a sclerosing agent in the treatment of varicose veins. OBJECTIVE:This review summarizes efficacy of polidocanol endovenous microfoam sclerotherapy ...
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
abstract::In the last three years, most efforts of virologists and immunologists involved in the field of HIV have been focussed on strategies aimed at eradicating the infection. So far, however, all attempts have been unsuccessful. Indeed, even if the currently available potent antiretroviral regimens are able to induce a prof...
journal_title:Expert opinion on investigational drugs
pub_type: 社论
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更新日期:2000-02-01 00:00:00
abstract:INTRODUCTION:The N-methyl-d-aspartate receptor-ionophore complex plays a key role in learning and memory and has efficacy in animals and humans with affective disorders. GLYX-13 is an N-methyl-d-aspartate receptor (NMDAR) glycine-site functional partial agonist and cognitive enhancer that also shows rapid antidepressan...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.852536
更新日期:2014-02-01 00:00:00
abstract:INTRODUCTION:Peripheral arterial disease (PAD) is a manifestation, and marker of severity, of a generalized atherosclerotic process. Antiplatelet therapy is recommended to prevent cardiovascular events but much of the evidence to support this is drawn from studies on older drugs. AREAS COVERED:In this review, the auth...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.974803
更新日期:2014-12-01 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::Despite advances in supportive care, septic shock remains a major cause of morbidity and mortality. With the identification of the systemic inflammatory response as a major component in the pathogenesis of the septic shock syndrome, much of the recent work has focused on modulating this response. This includes antiend...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.2.139
更新日期:2003-02-01 00:00:00
abstract::The utility of transgenic animal bioreactors for the production of complex therapeutic proteins is based on lower production costs, higher production capacities and safer, pathogen free products. Until gene therapy becomes broadly efficacious, transgenic-derived therapeutics are the most attractive alternative for pro...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.10.1683
更新日期:1998-10-01 00:00:00
abstract:BACKGROUND:Based partially on encouraging findings from preclinical models, interest has grown in therapeutic inhibition of NF-kappaB to limit inflammatory injury during sepsis. However, NF-kappaB also regulates protective responses, and predicting the net survival effects of such inhibition may be difficult. OBJECTIV...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903018880
更新日期:2009-08-01 00:00:00
abstract::Preclinical and clinical evidence support the effectiveness of neurotrophins in Alzheimer's disease (AD) and neurodegenerative diseases. Delivery of neurotrophins to target sites in the brain remains a major obstacle for their use in humans. Development of orally active agents that mimic the effects of nerve growth fa...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.10.1413
更新日期:1997-10-01 00:00:00
abstract::Considerable progress has been made with tyrosine kinase inhibitors. After long and sustained efforts, several tyrosine kinase inhibitors with convincing in vivo experimental antitumour properties such as CP-358,774, ZD 1839, CEP-751 are entering Phase I clinical trials. Significant in vivo experimental antitumour act...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.6.771
更新日期:1997-06-01 00:00:00
abstract::The annual meeting of the American Diabetes Association was held in Boston, MA. There were over 6500 participants, one-third from overseas, and 1103 papers were presented. Abstracts from the meeting have been published, from which abstract numbers are given below, e.g., (A141). Considerable progress has been made in u...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.8.1113
更新日期:1997-08-01 00:00:00