Abstract:
:A rapid expansion in precision medicine founded on the potential for durable clinical benefit through matching a drug to a predictive marker used to select patients has driven the development of targeted drugs with accompanied companion diagnostics for patient selection. Oncology has been at the forefront, with the improvements in patient survival notable. Increasing numbers of molecular subgroups require an equally increasing number (and new generation) of highly selective agents targeting inevitably lower incidence molecular segments, posing significant challenges for drug development. Innovative trial designs (umbrella or basket studies) are emerging as patient-centric approaches and public-private partnerships, cross-industry, government and non-profit sector collaborations are enabling implementation. Success will require continued innovation, new paradigms in oncology drug development and market approval and continued collaboration.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Hollingsworth SJdoi
10.1016/j.drudis.2015.10.005subject
Has Abstractpub_date
2015-12-01 00:00:00pages
1455-63issue
12eissn
1359-6446issn
1878-5832pii
S1359-6446(15)00382-7journal_volume
20pub_type
杂志文章,评审abstract::Translating academic medical research into new therapies is an important challenge for the biopharmaceutical industry and investment communities, which have historically favored later-stage assets with lower risk and clearer commercial value. The Stanford SPARK program is an innovative model for addressing this challe...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.03.015
更新日期:2017-07-01 00:00:00
abstract::For the past decade, the development of genomic technology has revolutionized modern biological research and drug discovery. Functional genomic analyses enable biologists to perform analysis of genetic events on a global scale and they have been widely used in gene discovery, biomarker determination, disease classific...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2009.05.005
更新日期:2009-08-01 00:00:00
abstract::The focus of high-throughput drug discovery has progressed through the genome and the transcriptome and is now moving towards more difficult problems in assessing the proteome, glycome and metabolome. Microarrays are currently the major tool in the assessment of gene expression via cDNA or RNA analysis; however, they ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/s1359-6446(03)02773-9
更新日期:2003-07-15 00:00:00
abstract::New therapies based on the use of biomolecules [e.g., proteins, peptides, and non-coding (nc)RNAs] have emerged during the past few years. Given their instability, adverse effects, and limited ability to cross cell membranes, delivery systems are required to fully reveal their biological potential. Sophisticated nanof...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.01.019
更新日期:2018-05-01 00:00:00
abstract::The biopharmaceutical industry is characterized by intense competition, high uncertainty, and strong dependence on scientific knowledge. We show that in order to succeed in this industry, firms need to be positioned along three strategic dimensions: the level of inter-firm R&D partnering, the level of diversification,...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2009.04.004
更新日期:2009-08-01 00:00:00
abstract::Chemokines are proinflammatory mediators that primarily control leukocyte migration into selected tissues and upregulation of adhesion receptors. They also have a role in pathological conditions that require neovascularization and are implicated in the suppression of viral replication. By interaction with their respec...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(98)01280-x
更新日期:1999-02-01 00:00:00
abstract::Inhibitors of epigenetic targets have entered clinical trials with some success, in particular for combined therapies. Like many other chemotherapeutics these new classes of molecules have dose-limiting toxicities and highly active metabolism in vivo resulting in lower efficacy than expected. This review presents drug...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.03.017
更新日期:2014-09-01 00:00:00
abstract::The development of any stem-cell-based therapy (and a potential one for deafness is no exception) relies on the generation of the necessary tools: 'cell drugs' that can be safely manufactured for their clinical application. An increasing body of work has focussed on the identification, in animal models, of potential s...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2010.02.006
更新日期:2010-04-01 00:00:00
abstract::With the aging of the general population, there is an increasing need for bone defect repair, prompting the development of reliable alternatives to autologous bone grafting, without the usually associated major drawbacks (i.e., limited volume and severe postoperative pain). Given the crucial role that miRNAs appear to...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.04.007
更新日期:2017-07-01 00:00:00
abstract::The nuclear receptors constitutive androstane receptor (CAR), pregnane X receptor (PXR) and vitamin D receptor (VDR) control a large array of genes that code for important proteins in humans including metabolic enzymes and transporters. 3D structures for the ligand-binding domain (LBD) of these receptors are abundantl...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2013.01.001
更新日期:2013-06-01 00:00:00
abstract::A more complete understanding of the mechanisms that drive autoimmune diseases has begun to be translated into therapeutic options with significant clinical consequences. A clear example of this is the introduction of biological therapies, which have provided new therapeutic avenues, as well as validated the mediators...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2009.07.002
更新日期:2009-10-01 00:00:00
abstract::Increasing evidence indicates that extracellular vesicles (EVs) are key players in undesirable cell-cell communication in cancer. However, the release of EVs is not unique to cancer cells; normal cells release EVs to perform physiological roles. Thus, selective inhibition of EV release from cancer cells is desirable. ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.03.006
更新日期:2018-06-01 00:00:00
abstract::The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologi...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2008.02.006
更新日期:2008-07-01 00:00:00
abstract::A drug has entered clinical trials that contains a recombinant version of the main extract from mistletoe, adn holds promise for cancer patients. ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(02)02571-0
更新日期:2003-01-15 00:00:00
abstract::Research consortia in Europe often compete with each other for skills, human and technical resources and, eventually, recognition of the scientific impact of their work. In response to the same EU Horizon2020 call, we received funding for our research project proposals to identify and validate novel drug targets for c...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.01.009
更新日期:2020-04-01 00:00:00
abstract::The lack of structural information on hepatitis C virus (HCV) surface proteins has so far hampered the development of effective vaccines. Recently, two crystallographic structures have described the core portion (E2c) of E2 surface glycoprotein, the primary mediator of HCV entry. Despite the importance of these studie...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.08.011
更新日期:2014-12-01 00:00:00
abstract::Natural products have been, and continue to be, a major source of pharmacologically active substances from which drugs can be developed. Currently, tumor necrosis factor-alpha (TNF-alpha) inhibitors from natural origins are being advanced for the treatment of inflammatory disorders. Elevated TNF-alpha synthesis has be...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2006.06.002
更新日期:2006-08-01 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::Drug-induced liver injury (DILI) is of significant concern to drug development and regulatory review because of the limited success with existing preclinical models. For developing alternative methods, a large drug list is needed with known DILI severity and toxicity. We augmented the DILIrank data set [annotated usin...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.09.022
更新日期:2020-01-01 00:00:00
abstract::Identifying new indications for existing drugs creates new therapeutic options while bypassing much of the costs and time involved with bringing a new drug to market. The rediscovery of a generic drug, however, is a challenging pursuit because there is no formal regulatory approach and a lack of economic interest by p...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2017.08.008
更新日期:2018-01-01 00:00:00
abstract::The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are ligand-activated nuclear receptors (NRs) that are notorious for their role in drug metabolism, causing unintended drug-drug interactions and decreasing drug efficacy. They control the xenobiotic detoxification system by regulating the exp...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.01.021
更新日期:2019-03-01 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
abstract::Since being introduced to the field of drug discovery at Zeneca Pharmaceuticals in 1991, it has become apparent to me that a blizzard of revolutionary novel approaches has swept through the pharmaceutical industry. Now, the discovery process has become completely transformed and the race to develop commercially succes...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(98)01289-6
更新日期:1999-01-01 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::Poly(lactic-co-glycolic acid) (PLGA), a US Food and Drug Administration (FDA)-approved copolymer, has been exploited widely in the design of nanoparticles because it is biodegradable, biocompatible, protects the drug molecules from degradation, and aids in producing sustained and targeted delivery. However, certain co...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.09.018
更新日期:2015-01-01 00:00:00
abstract::Nonalcoholic steatohepatitis (NASH) is emerging as a major public health issue for the 21st century and is associated with significant liver-related morbidity and mortality. At present, there are no approved drug therapies for NASH. Consequently, NASH has become the focus of significant public and private research and...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.09.020
更新日期:2019-02-01 00:00:00
abstract::Model-based drug discovery (MBDDx) aims to build and continuously improve the quantitative understanding of the relation between drug exposure (target engagement) efficacy and safety, to support target validation; to define compound property criteria for lead optimization and safety margins; to set the starting dose; ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2013.05.012
更新日期:2013-08-01 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 pharmacological and adverse effect profiles of the two approved therapies for IPF make the development of new therapies challenging. Considering the similarity of the characteristics of drug candidates to Standard of Care is important in defining positioning and development strategies for this disease. ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.09.019
更新日期:2020-12-01 00:00:00
abstract::3D bioprinting has emerged as the intersection between chemistry, biology and technology. Through its integration of cells, biocompatible materials and robotic-controlled dispensing systems, the process enables the production of structures that are biomimetic and functional, thus revolutionizing the concept of tissue ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.09.012
更新日期:2019-01-01 00:00:00