Abstract:
:Immunotherapies have changed the treatment strategy of some types of tumor including melanoma and, more recently, non-small-cell lung cancer (NSCLC). Immune checkpoints are crucial for the maintenance of self-tolerance and it is known that some tumors use checkpoint systems to evade antitumor immune response. The treatment of advanced NSCLC by immune-checkpoint blockade targeting the programmed cell death protein-1 (PD1/PDL1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) pathways has led to significant clinical benefit either as monotherapy or in combination therapy. Moreover, checkpoint receptors such as lymphocyte activation gene 3 protein (LAG3), T-cell immunoglobulin mucin domain 3 (TIM3) and killer immunoglobulin-like receptors (KIRs) are also being investigated as potential immunotherapeutic targets. This review focuses on the mechanisms of action of the main checkpoint inhibitors in lung cancer and presents the most relevant results from preclinical and clinical studies on immune-based treatments.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Dal Bello MG,Alama A,Coco S,Vanni I,Grossi Fdoi
10.1016/j.drudis.2017.05.016subject
Has Abstractpub_date
2017-08-01 00:00:00pages
1266-1273issue
8eissn
1359-6446issn
1878-5832pii
S1359-6446(17)30299-4journal_volume
22pub_type
杂志文章,评审abstract::Proteomic-based techniques provide a powerful tool for identifying the full spectrum of protein targets of a drug, elucidating its mechanism(s) of action, and identifying biomarkers of its efficacy and safety. Herein, we outline the technological advancements in the field, and illustrate the contribution of proteomics...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.03.001
更新日期:2017-06-01 00:00:00
abstract::Three-dimensional (3D) pharmacophore modeling is a technique for describing the interaction of a small molecule ligand with a macromolecular target. Since chemical features in a pharmacophore model are well known and highly transparent for medicinal chemists, these models are intuitively understandable and have been i...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2007.09.007
更新日期:2008-01-01 00:00:00
abstract::Clear links between cancer and cellular signaling triggered by the insulin-like growth factor-I (IGF-I) receptor (IGF-IR) and its cognate ligands (IGF-I and IGF-II) have been reported throughout the past two decades. Experimental results suggest that the pharmaceutical targeting of this signaling pathway could be bene...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(05)03512-9
更新日期:2005-08-01 00:00:00
abstract::Following multiple warnings from governments and health organisations, there has been renewed investment, led by the public sector, in the discovery of novel antimicrobials to meet the challenge of rising levels of drug-resistant infection, particularly in the case of resistance to antibiotics. Initiatives have also b...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.11.015
更新日期:2019-02-01 00:00:00
abstract::Senescence forms a universal block to tumorigenesis which impacts on all hallmarks of cancer, making it an attractive target for drug discovery. Therefore a strategy must be devised to focus this broad potential into a manageable drug discovery programme. Several issues remain to be addressed including the lack of rob...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.01.019
更新日期:2012-03-01 00:00:00
abstract::The paradigm of central nervous system (CNS) drug discovery has mostly relied on traditional approaches of rodent models or cell-based in vitro models. Owing to the issues of species differences between humans and rodents, it is difficult to correlate the robustness of data for neurodevelopmental studies. With advance...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.11.010
更新日期:2020-02-01 00:00:00
abstract::Covalent allosteric modulators possess the pharmacological advantages (high potency, extended duration of action and low drug resistance) of covalent ligands and the additional benefit of the higher specificity and lower toxicity of allosteric modulators. This approach is gaining increasing recognition as a valuable t...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.11.013
更新日期:2017-02-01 00:00:00
abstract::Immunoinformatics has recently emerged as a critical field for accelerating immunology research. Although still an evolving process, computational models now play instrumental roles, not only in directing the selection of key experiments, but also in the formulation of new testable hypotheses through detailed analysis...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2009.04.001
更新日期:2009-07-01 00:00:00
abstract::There is a continuing need to hasten and improve protein-ligand docking to facilitate the next generation of drug discovery. As the drug-like chemical space reaches into the billions of molecules, increasingly powerful computer systems are required to probe, as well as tackle, the software engineering challenges neede...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.06.023
更新日期:2016-10-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is one of the most complex motor neuron diseases. Even though scientific discoveries are accelerating with an unprecedented pace, to date more than 30 clinical trials have ended with failure and staggering frustration. There are too many compounds that increase life span in mice, bu...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2013.10.014
更新日期:2014-04-01 00:00:00
abstract::Compelling new evidence supports the idea that regulatory T cells play a major role in our immune system. Several subsets of these regulators have been identified recently. Differences in the phenotypical and functional characteristics of these subsets have immunological implications. From our growing knowledge of the...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(03)03021-6
更新日期:2004-04-01 00:00:00
abstract::Molecular chirality is a fundamental consideration in drug discovery, one necessary to understand and describe biological targets as well as to design effective pharmaceutical agents. Enantioselective chromatography has played an increasing role not only as an analytical tool for chiral analyses, but also as a prepara...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(05)03407-0
更新日期:2005-04-15 00:00:00
abstract::Biomedical scientists tend to focus on only a small fraction of the proteins encoded by the human genome despite overwhelming genetic evidence that many understudied proteins are important for human disease. One of the best ways to interrogate the function of a protein and to determine its relevance as a drug target i...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2019.06.020
更新日期:2019-11-01 00:00:00
abstract::The clinical advancement of HIV-1 attachment inhibitors was hindered initially by poor bioavailability. Attempts to identify improved candidates revealed that solubility and dissolution-rate-limited absorption are barriers to achieving adequate antiviral plasma levels. This was mitigated by forming nanosized drugs or ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2014.03.025
更新日期:2014-09-01 00:00:00
abstract::Benford's law states that the distribution of the first digit of many data sets is not uniform. The first digit of any random number will be 1 almost 30% of the time, and larger digits occur as the first digit with lower and lower frequency, to the point where 9 occurs as a first digit only 5% of the time. Here, we de...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2010.03.003
更新日期:2010-05-01 00:00:00
abstract::Atomic force microscopy is being used ever more widely in biological imaging, because of its unique ability to provide structural information at the single molecule level and under near-physiological conditions. Detailed topographic images of potential drug targets, such as proteins and DNA, have been produced, and th...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(03)02905-2
更新日期:2004-01-15 00:00:00
abstract::Oral delivery of peptides and proteins remains an attractive alternative to parenteral delivery and has challenged various attempts at delivery development. Incorporation of new tools into the delivery systems that can raise membrane permeability of macromolecules is essential to attain high oral bioavailability that ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2006.08.005
更新日期:2006-10-01 00:00:00
abstract::Confronted with the need to significantly raise the productivity of remotely located chemistry CROs Pfizer embraced a commitment to continuous improvement which leveraged the tools from both Lean Six Sigma and queue management theory to deliver positive measurable outcomes. During 2012 cycle times were reduced by 48% ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2013.07.017
更新日期:2014-03-01 00:00:00
abstract::Peptide-based drugs are now viable alternatives to biopharmaceuticals, such as antibodies. Most of the past limitations of peptides have been removed by new technologies, so that peptides now face similar hurdles to antibodies. Phage-display technology provides novel peptides that bind protein targets with high affini...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(04)03104-6
更新日期:2004-06-15 00:00:00
abstract::The popularity of machine learning (ML) across drug discovery continues to grow, yielding impressive results. As their use increases, so do their limitations become apparent. Such limitations include their need for big data, sparsity in data, and their lack of interpretability. It has also become apparent that the tec...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.12.003
更新日期:2020-12-05 00:00:00
abstract::Antibodies (Abs) are regarded as a newly emerging form of therapeutics that can provide passive protection against influenza. Although the application of genomics in clinics has increased dramatically, the number of therapeutics available for the treatment of many diseases remains insufficient. To translate genomics i...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.06.008
更新日期:2016-10-01 00:00:00
abstract::The operational model of agonism assumes that the maximum effect a particular receptor system can achieve (the Em parameter) is fixed. Em estimates are above but close to the asymptotic maximum effects of endogenous agonists. The concept of Em is contradicted by superagonists and those positive allosteric modulators t...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2012.12.004
更新日期:2013-04-01 00:00:00
abstract::Concerns emanating from the medical community about the safety and efficacy of biosimilars indicate an increasing distrust of the outcome of the drug regulatory process. To illustrate this, we analysed the creation of the European biosimilar regulatory framework, specifically focussing on the guidelines outlining appr...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2011.09.018
更新日期:2012-02-01 00:00:00
abstract::Osteoarthritis (OA), the most common and disabling form of arthritic disease, is characterized by a slow and progressive degeneration of articular cartilage. Its etiology is multifactorial and includes genetic predisposition, obesity and aging. In addition to the cartilage itself, OA also involves the surrounding tiss...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2011.01.004
更新日期:2011-05-01 00:00:00
abstract::In vitro human small intestine models play a crucial part in preclinical drug development. Although conventional 2D systems possess many advantages, such as facile accessibility and high-throughput capability, they can also provide misleading results due to their relatively poor recapitulation of in vivo physiology. S...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.05.003
更新日期:2014-10-01 00:00:00
abstract::Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(00)01619-6
更新日期:2001-02-01 00:00:00
abstract::Data mining of available biomedical data and information has greatly boosted target discovery in the 'omics' era. Target discovery is the key step in the biomarker and drug discovery pipeline to diagnose and fight human diseases. In biomedical science, the 'target' is a broad concept ranging from molecular entities (s...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2011.12.006
更新日期:2012-02-01 00:00:00
abstract::Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(00)01674-3
更新日期:2001-03-01 00:00:00
abstract::Corneal blindness caused by limbal stem cell deficiency (LSCD) is a prevailing disorder worldwide. Clinical outcomes for LSCD therapy using amniotic membrane (AM) are unpredictable. Hydrogels can eliminate limitations of standard therapy for LSCD, because they present all the advantages of AM (i.e. biocompatibility, i...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.07.012
更新日期:2013-01-01 00:00:00
abstract::As the field of ocular drug delivery grows so does the potential for novel drug discovery or reformulation in lesser-known diseases of the eye. In particular, rare corneal diseases are an interesting area of research because drug delivery is limited to the outermost tissue of the eye. This review will highlight the op...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.03.005
更新日期:2019-08-01 00:00:00