Abstract：
:The occurrence of drug resistance in oncology accounts for treatment failure and relapse of diverse tumor types. Cancers contain cells at various stages of differentiation together with a limited number of 'cancer-initiating cells' able to self-renew and divide asymmetrically, driving tumorigenesis. Cancer-initiating cells display a range of self-defense systems that include almost all mechanisms of drug-resistance. Different molecular pathways and markers, identified in this malignant sub-population, are becoming targets for novel compounds and for monoclonal antibodies, which may be combined with conventional drugs. These interventions might eliminate drug-resistant cancer-initiating cells and lead to remission or cure of cancer patients.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Alama A,Orengo AM,Ferrini S,Gangemi Rdoi
10.1016/j.drudis.2011.02.005subject
Has Abstractpub_date
2012-05-01 00:00:00pages
435-42issue
9-10eissn
1359-6446issn
1878-5832pii
S1359-6446(11)00037-7journal_volume
17pub_type
杂志文章,评审abstract：:Drug-delivery technologies for modified drug release have been in existence for decades, but their utilization has been largely limited to post-launch efforts improving therapeutic outcomes. Recently, they have gained renewed importance because the pharmaceutical industry is steadily shifting to a more integrated disc...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.12.008
更新日期：2020-12-14 00:00:00
abstract：:One of the most challenging problems, if not the most challenging, in drug development is not to develop drugs to treat diseases of the central nervous system (CNS), but to manage to distribute them to the CNS across the blood-brain barrier (BBB) using transvascular routes following intravenous administration. The dev...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2008.09.005
更新日期：2008-12-01 00:00:00
abstract：:Mice have been excellent surrogates for studying neutrophil biology and, furthermore, murine models of human disease have provided fundamental insights into the roles of human neutrophils in innate immunity. The emergence of novel humanized mice and high-diversity mouse populations offers the research community innova...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.03.018
更新日期：2020-06-01 00:00:00
abstract：:The Science for Life Laboratory Drug Discovery and Development (SciLifeLab DDD) platform reaches out to Swedish academia with an industry-standard infrastructure for academic drug discovery, supported by earmarked funds from the Swedish government. In this review, we describe the build-up and operation of the platform...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.06.026
更新日期：2016-10-01 00:00:00
abstract：:Stimulation of bone regeneration using growth factors is a promising approach for musculoskeletal regenerative engineering. However, common limitations with protein growth factors, such as high manufacturing costs, protein instability, contamination issues, and unwanted immunogenic responses of the host reduce potenti...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.01.012
更新日期：2014-06-01 00:00:00
abstract：:In recent years there has been a dramatic increase in the number of freely accessible online databases serving the chemistry community. The internet provides chemistry data that can be used for data-mining, for computer models, and integration into systems to aid drug discovery. There is however a responsibility to en...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.02.013
更新日期：2012-07-01 00:00:00
abstract：:In therapeutic areas aimed at developing an orally administered drug, the pharmacokinetic profile of a drug candidate after oral administration in vivo is pivotal in evaluating its success. This can be done by monitoring the plasma concentration versus time after dosing and calculating the area under the curve (AUC). ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(98)01299-9
更新日期：1999-05-01 00:00:00
abstract：:Drug-induced liver injury (DILI) is a leading cause of drugs failing during clinical trials and being withdrawn from the market. Comparative analysis of drugs based on their DILI potential is an effective approach to discover key DILI mechanisms and risk factors. However, assessing the DILI potential of a drug is a ch...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2011.05.007
更新日期：2011-08-01 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)01551-8
更新日期：2000-09-01 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：:The cachexia syndrome, characterized by a marked weight loss, anorexia, asthenia and anaemia, is invariably associated with the growth of a tumour and leads to a malnutrition status caused by the induction of anorexia or decreased food intake. In addition, the competition for nutrients between the tumour and the host ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(03)02826-5
更新日期：2003-09-15 00:00:00
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 trea...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.05.016
更新日期：2017-08-01 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：:Post-translational modifications, such as acetylation or phosphorylation, play a crucial role in the regulation of gene transcription in eukaryotes. Different subtypes of histone acetyl transferases (HATs) catalyze the acetylation of histones on specific lysine residues. A potential role of HATs in the pathology of ca...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.06.008
更新日期：2009-10-01 00:00:00
abstract：:Protein expression therapy using nucleic acid macromolecules (NAMs) as a new paradigm in medicine has recently gained immense therapeutic potential. With the advancement of nonviral delivery it has been possible to target NAMs against cancer, immunodeficiency and infectious diseases. Owing to the complex and fragile s...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2015.11.012
更新日期：2016-03-01 00:00:00
abstract：:Lack of predictability of clinical efficacy and safety is an important problem facing pharmaceutical research today. Translational PK-PD has the ability to integrate data generated from diverse test platforms during discovery and development in a mechanistic framework. Therefore, successful implementation of translati...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.10.002
更新日期：2007-12-01 00:00:00
abstract：:Patients can mount sustained immune responses to protein therapeutics with the production of neutralizing antibodies (NAbs) that can compromise efficacy or safety of these drugs. Dendritic cells (DCs) are required for immunoglobulin (Ig) isotype switching and the production of IgG, a process involving presentation of ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.06.005
更新日期：2007-08-01 00:00:00
abstract：:Rare-disease drug development is both scientifically and commercially challenging. This case study highlights Agilis Biotherapeutics (Agilis), a small private biotechnology company that has developed the most clinically advanced adeno-associated virus (AAV) gene therapy for the brain. In an international collaboration...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.12.006
更新日期：2019-03-01 00:00:00
abstract：:Cocaine is a major drug of abuse whose devastating effects have captured the attention of health officials and policy makers. Based upon the alarming health and crime-related costs associated with the use of this powerful reinforcing drug, immediate therapies are needed for the treatment of cocaine addiction. In this ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(99)01332-x
更新日期：1999-07-01 00:00:00
abstract：:Following the introduction of antibiotic therapy and widespread inoculations, cardiovascular diseases have leapt ahead of infectious diseases in terms of prevalence in much of the developed and developing world. Herein, we assess FDA-approved drugs for the treatment of cardiovascular diseases. The drug development ent...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2014.09.001
更新日期：2016-01-01 00:00:00
abstract：:Understanding skin metabolism is important when considering drug discovery and safety assessment. This review compares xenobiotic skin metabolism in ex vivo skin to reconstructed human skin and reconstructed human epidermis models, concentrating on phase I and phase II enzymes. Reports on phase I enzymes are more abun...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.06.002
更新日期：2019-09-01 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：: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：: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：:For drug discovery, historical experience is always of significance. Through examining the history of traditional medicines, we find that these medicines have more implications for drug discovery than just providing new chemical entities. The history of traditional medicines indicates that they depended more on the co...
journal_title：Drug discovery today
pub_type： 历史文章,杂志文章
doi：10.1016/j.drudis.2008.07.002
更新日期：2009-02-01 00:00:00
abstract：:Drugs that covalently bond to their biological targets have a long history in drug discovery. A look at drug approvals in recent years suggests that covalent drugs will continue to make impacts on human health for years to come. Although fraught with concerns about toxicity, the high potencies and prolonged effects ac...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2015.05.005
更新日期：2015-09-01 00:00:00
abstract：:Kidneys have a major role in normal physiology and metabolic homeostasis. Loss or impairment of kidney function is a common occurrence in several metabolic disorders, including hypertension and diabetes. Chronic kidney disease (CKD) affect nearly 10% of the population worldwide; ranks 18th in the list of causes of dea...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.04.020
更新日期：2017-07-01 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：: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：: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
