Targeting cancer-initiating cell drug-resistance: a roadmap to a new-generation of cancer therapies?


: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.


Drug Discov Today


Drug discovery today


Alama A,Orengo AM,Ferrini S,Gangemi R




Has Abstract


2012-05-01 00:00:00














  • Modulating target engagement of small molecules via drug delivery: approaches and applications in drug discovery and development.

    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


    authors: Yang W,Bhattachar SN,Patel PJ,Landis M,Patel D,Reid DL,Duvnjak Romic M

    更新日期:2020-12-14 00:00:00

  • The targeted delivery of cancer drugs across the blood-brain barrier: chemical modifications of drugs or drug-nanoparticles?

    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


    authors: Juillerat-Jeanneret L

    更新日期:2008-12-01 00:00:00

  • Improved mouse models and advanced genetic and genomic technologies for the study of neutrophils.

    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


    authors: Hosur V,Skelly DA,Francis C,Low BE,Kohar V,Burzenski LM,Amiji MM,Shultz LD,Wiles MV

    更新日期:2020-06-01 00:00:00

  • Open for collaboration: an academic platform for drug discovery and development at SciLifeLab.

    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


    authors: Arvidsson PI,Sandberg K,Forsberg-Nilsson K

    更新日期:2016-10-01 00:00:00

  • Delivery of small molecules for bone regenerative engineering: preclinical studies and potential clinical applications.

    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


    authors: Laurencin CT,Ashe KM,Henry N,Kan HM,Lo KW

    更新日期:2014-06-01 00:00:00

  • Towards a gold standard: regarding quality in public domain chemistry databases and approaches to improving the situation.

    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


    authors: Williams AJ,Ekins S,Tkachenko V

    更新日期:2012-07-01 00:00:00

  • Novel procedure for rapid pharmacokinetic screening of discovery compounds in rats.

    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


    authors: Cox KA,Dunn-Meynell K,Korfmacher WA,Broske L,Nomeir AA,Lin CC,Cayen MN,Barr WH

    更新日期:1999-05-01 00:00:00

  • FDA-approved drug labeling for the study of drug-induced liver injury.

    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


    authors: Chen M,Vijay V,Shi Q,Liu Z,Fang H,Tong W

    更新日期:2011-08-01 00:00:00

  • Monitor: molecules and profiles.

    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


    authors: Lloyd AW

    更新日期:2000-09-01 00:00:00

  • Use of Benford's law in drug discovery data.

    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


    authors: Orita M,Moritomo A,Niimi T,Ohno K

    更新日期:2010-05-01 00:00:00

  • Catabolic mediators as targets for cancer cachexia.

    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


    authors: Argilés JM,Moore-Carrasco R,Busquets S,López-Soriano FJ

    更新日期:2003-09-15 00:00:00

  • Understanding the checkpoint blockade in lung cancer immunotherapy.

    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


    authors: Dal Bello MG,Alama A,Coco S,Vanni I,Grossi F

    更新日期:2017-08-01 00:00:00

  • Preparing for the new millennium.

    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


    authors: Tranter D

    更新日期:1999-01-01 00:00:00

  • Histone acetyl transferases as emerging drug targets.

    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


    authors: Dekker FJ,Haisma HJ

    更新日期:2009-10-01 00:00:00

  • Critical considerations for developing nucleic acid macromolecule based drug products.

    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


    authors: Muralidhara BK,Baid R,Bishop SM,Huang M,Wang W,Nema S

    更新日期:2016-03-01 00:00:00

  • The role of mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) modelling in translational research of biologics.

    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


    authors: Agoram BM,Martin SW,van der Graaf PH

    更新日期:2007-12-01 00:00:00

  • Immunogenicity of protein therapeutics and the interplay between tolerance and antibody responses.

    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


    authors: Barbosa MD,Celis E

    更新日期:2007-08-01 00:00:00

  • Acceleration of rare disease therapeutic development: a case study of AGIL-AADC.

    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


    authors: Das S,Huang S,Lo AW

    更新日期:2019-03-01 00:00:00

  • Dopaminergic agents for the treatment of cocaine abuse.

    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


    authors: Smith MP,Hoepping A,Johnson KM,Trzcinska M,Kozikowski AP

    更新日期:1999-07-01 00:00:00

  • An analysis of FDA-approved drugs for cardiovascular diseases.

    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


    authors: Kinch MS,Surovtseva Y,Hoyer D

    更新日期:2016-01-01 00:00:00

  • Skin metabolism phase I and phase II enzymes in native and reconstructed human skin: a short review.

    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


    authors: Kazem S,Linssen EC,Gibbs S

    更新日期:2019-09-01 00:00:00

  • Towards the use of hydrogels in the treatment of limbal stem cell deficiency.

    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


    authors: Wright B,Mi S,Connon CJ

    更新日期:2013-01-01 00:00:00

  • Recent progress toward biomarker identification in osteoarthritis.

    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


    authors: De Ceuninck F,Sabatini M,Pastoureau P

    更新日期:2011-05-01 00:00:00

  • Blocking the insulin-like growth factor-I receptor as a strategy for targeting cancer.

    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


    authors: Hofmann F,García-Echeverría C

    更新日期:2005-08-01 00:00:00

  • Where is the hope for drug discovery? Let history tell the future.

    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


    authors: Kong DX,Li XJ,Zhang HY

    更新日期:2009-02-01 00:00:00

  • Covalent inhibitors in drug discovery: from accidental discoveries to avoided liabilities and designed therapies.

    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


    authors: Bauer RA

    更新日期:2015-09-01 00:00:00

  • Noncoding RNA and epigenetic gene regulation in renal diseases.

    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


    authors: Kota SK,Kota SB

    更新日期:2017-07-01 00:00:00

  • Revival of the regulatory T cell: new targets for drug development.

    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


    authors: Sutmuller RP,Offringa R,Melief CJ

    更新日期:2004-04-01 00:00:00

  • Model-based drug discovery: implementation and impact.

    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


    authors: Visser SA,Aurell M,Jones RD,Schuck VJ,Egnell AC,Peters SA,Brynne L,Yates JW,Jansson-Löfmark R,Tan B,Cooke M,Barry ST,Hughes A,Bredberg U

    更新日期:2013-08-01 00:00:00

  • Is the oral route possible for peptide and protein drug delivery?

    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


    authors: Morishita M,Peppas NA

    更新日期:2006-10-01 00:00:00