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














  • Commercially bioavailable proprietary technologies and their marketed products.

    abstract::In this review, we discuss the methodologies and platform technologies for enhancing the oral bioavailability of poorly soluble drugs. We also highlight the mechanisms of formulation technologies for improving desired physicochemical attributes of active substances. We focus on various commercial technologies, along w...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Alam MA,Al-Jenoobi FI,Al-Mohizea AM

    更新日期:2013-10-01 00:00:00

  • Nanovehicles for co-delivery of anticancer agents.

    abstract::Effective cancer treatment remains a significant challenge in human healthcare. Although many different types of cancer therapy have been tested, scientists have now concluded that combinations of drugs, or drugs plus gene therapy, can target multiple pathways to fight cancer. Nanovehicles can increase drug uptake ins...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Zeinali M,Abbaspour-Ravasjani S,Ghorbani M,Babazadeh A,Soltanfam T,Santos AC,Hamishehkar H,Hamblin MR

    更新日期:2020-08-01 00:00:00

  • Target 2035: probing the human proteome.

    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


    authors: Carter AJ,Kraemer O,Zwick M,Mueller-Fahrnow A,Arrowsmith CH,Edwards AM

    更新日期:2019-11-01 00:00:00

  • Atomic force microscopy and drug discovery.

    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


    authors: Edwardson JM,Henderson RM

    更新日期:2004-01-15 00:00:00

  • The promise of a virtual lab in drug discovery.

    abstract::To date, the life sciences 'omics' revolution has not lived up to the expectation of boosting the drug discovery process. The major obstacle is dealing with the volume and diversity of data generated. An enhanced-science (e-science) approach based on remote collaboration, reuse of data and methods, and supported by a ...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Rauwerda H,Roos M,Hertzberger BO,Breit TM

    更新日期:2006-03-01 00:00:00

  • pH-dependent ileocolonic drug delivery, part I: in vitro and clinical evaluation of novel systems.

    abstract::After the pH dependency of novel pH-dependent ileocolonic drug delivery systems is confirmed in vitro, their performance should be evaluated in human volunteers. ...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Broesder A,Woerdenbag HJ,Prins GH,Nguyen DN,Frijlink HW,Hinrichs WLJ

    更新日期:2020-08-01 00:00:00

  • Molecular diversity and its analysis.

    abstract::We have recently developed a novel strategy for the rational design of compounds. This 'in silico screening' approach is based on the design and screening of virtual combinatorial libraries. Screening is performed using defined rules derived from a comprehensive description of active and inactive molecules in a releva...

    journal_title:Drug discovery today

    pub_type: 杂志文章


    authors: Gorse D,Rees A,Kaczorek M,Lahana R

    更新日期:1999-06-01 00:00:00

  • The role of fragment-based and computational methods in polypharmacology.

    abstract::Polypharmacology-based strategies are gaining increased attention as a novel approach to obtaining potentially innovative medicines for multifactorial diseases. However, some within the pharmaceutical community have resisted these strategies because they can be resource-hungry in the early stages of the drug discovery...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Bottegoni G,Favia AD,Recanatini M,Cavalli A

    更新日期:2012-01-01 00:00:00

  • Engineered miniaturized models of musculoskeletal diseases.

    abstract::The musculoskeletal system is an incredible machine that protects, supports and moves the human body. However, several diseases can limit its functionality, compromising patient quality of life. Designing novel pathological models would help to clarify the mechanisms driving such diseases, identify new biomarkers and ...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Bersini S,Arrigoni C,Lopa S,Bongio M,Martin I,Moretti M

    更新日期:2016-09-01 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

  • Advanced glycation end products in diabetes, cancer and phytochemical therapy.

    abstract::The irreversible glycation and oxidation of proteins and lipids produces advanced glycation end products (AGEs). These modified AGEs are triggered to bind the receptor for AGE (RAGE), thereby activating its downstream signaling pathways, such as nuclear factor (NF)-κB and phosphoinositide 3-kinase (PI3K)/Akt, ultimate...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Dariya B,Nagaraju GP

    更新日期:2020-09-01 00:00:00

  • Broad-scale analysis of thermodynamic signatures in medicinal chemistry: are enthalpy-favored binders the better development option?

    abstract::Thermodynamic profiles of ligand binding, particularly enthalpically favored binding signatures, have been suggested as a criterion to support the decision-making process around which compounds to select for further optimization in drug development. The concept was enthusiastically taken up, but turned out to be too s...

    journal_title:Drug discovery today

    pub_type: 杂志文章


    authors: Klebe G

    更新日期:2019-04-01 00:00:00

  • Nitric oxide: a drug target for glaucoma revisited.

    abstract::A reduction in intraocular pressure (IOP) is the only recognized therapy for glaucoma. Hence, drugs exhibiting ocular hypotensive effects are important targets for antiglaucomatous drug development. IOP is determined by the equilibrium of aqueous humor production and outflow through either the trabecular meshwork or t...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Garhöfer G,Schmetterer L

    更新日期:2019-08-01 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: Barlocco D,Langston S,Tranter D

    更新日期:2001-08-01 00:00:00

  • The microRNA landscape of cutaneous squamous cell carcinoma.

    abstract::Cutaneous squamous cell carcinoma (cSCC) is a keratinocyte-derived skin tumor. It is the second-most-common cancer affecting the Caucasian population and is responsible for >20% of all skin-cancer-related deaths. The estimated incidence of non-melanoma skin cancer in the USA is >1000000 cases per year, of which roughl...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Konicke K,López-Luna A,Muñoz-Carrillo JL,Servín-González LS,Flores-de la Torre A,Olasz E,Lazarova Z

    更新日期:2018-04-01 00:00:00

  • Gastric bypass surgery mimetic approaches.

    abstract::Gastric bypass surgery is effectively a polypharmacological approach for treatment of obesity, type 2 diabetes and nonalcoholic steatohepatitis (NASH). The gastric bypass mimetic approaches reviewed are fixed-dose combinatorial pharmacological approaches. There are two key concepts incorporated into these gastric bypa...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Boettcher BR

    更新日期:2017-08-01 00:00:00

  • Targeting the Achilles heel of the hepatitis B virus: a review of current treatments against covalently closed circular DNA.

    abstract::Chronic infection with hepatitis B virus (HBV) often leads to the development of liver cancer and cirrhosis, creating immense sociological, clinical and economic burdens worldwide. Although current anti-HBV medications manage to control the disease progression and help restore normal liver functions, they often fail t...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Ahmed M,Wang F,Levin A,Le C,Eltayebi Y,Houghton M,Tyrrell L,Barakat K

    更新日期:2015-05-01 00:00:00

  • Renaissance of cancer therapeutic antibodies.

    abstract::In the past five years therapeutic monoclonal antibodies have established themselves as perhaps the most important and rapidly expanding class of therapeutic drugs. More than 25% of pharmacological agents that are currently under development are based on antibodies and the total income generated from them in 2002 exce...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Glennie MJ,van de Winkel JG

    更新日期:2003-06-01 00:00:00

  • Magnetic nanoformulations for prostate cancer.

    abstract::Magnetic nanoparticles (MNPs) play a vital role for improved imaging applications. Recently, a number of studies demonstrate MNPs can be applied for targeted delivery, sustained release of therapeutics, and hyperthermia. Based on stable particle size and shape, biocompatibility, and inherent contrast enhancement chara...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Chowdhury P,Roberts AM,Khan S,Hafeez BB,Chauhan SC,Jaggi M,Yallapu MM

    更新日期:2017-08-01 00:00:00

  • A modern in vivo pharmacokinetic paradigm: combining snapshot, rapid and full PK approaches to optimize and expedite early drug discovery.

    abstract::Successful drug discovery relies on the selection of drug candidates with good in vivo pharmacokinetic (PK) properties as well as appropriate preclinical efficacy and safety profiles. In vivo PK profiling is often a bottleneck in the discovery process. In this review, we focus on the tiered in vivo PK approaches imple...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Li C,Liu B,Chang J,Groessl T,Zimmerman M,He YQ,Isbell J,Tuntland T

    更新日期:2013-01-01 00:00:00

  • The development of molecular clamps as drugs.

    abstract::Some enzymes catalyze the modification of an ensemble of substrates in vivo and, as a consequence, are not ideal targets for active-site-directed drugs. One solution to inhibiting such multisubstrate enzymes would be a drug that binds tightly to only one substrate, which prevents the binding of that substrate to the e...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Weiss ST,McIntyre NR,McLaughlin ML,Merkler DJ

    更新日期:2006-09-01 00:00:00

  • Delivery of epidrugs.

    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


    authors: el Bahhaj F,Dekker FJ,Martinet N,Bertrand P

    更新日期:2014-09-01 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

  • Top 100 bestselling drugs represent an arena struggling for new FDA approvals: drug age as an efficiency indicator.

    abstract::We analyzed a list of the top 100 bestselling drugs as a struggling market for new FDA approvals. Using the time from drug approval by the FDA as a measure of drug age, our analysis showed that the top 100 bestselling drugs are getting older. This reflects the stalled launch of new drugs into the market during recent ...

    journal_title:Drug discovery today

    pub_type: 杂志文章


    authors: Polanski J,Bogocz J,Tkocz A

    更新日期:2015-11-01 00:00:00

  • Developments in microarray technologies.

    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


    authors: Howbrook DN,van der Valk AM,O'Shaughnessy MC,Sarker DK,Baker SC,Lloyd AW

    更新日期:2003-07-15 00:00:00

  • Stapled peptide induces cancer cell death.

    abstract::Hydrocarbon stapling could enable peptides from the key domains of natural proteins to be used therapeutically. Using the technique on a peptide involved in apoptosis, researchers have succeeded in destroying cancer cells in a mouse model of leukaemia. ...

    journal_title:Drug discovery today

    pub_type: 新闻


    authors: Whelan J

    更新日期:2004-11-01 00:00:00

  • Chemoproteomics-driven drug discovery: addressing high attrition rates.

    abstract::The advent of multiple high-throughput technologies has brought drug discovery round almost full circle, from pharmacological testing of compounds in vivo to engineered molecular target assays and back to integrated phenotypic screens in cells and organisms. In the past, primary screens to identify new pharmacological...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Hall SE

    更新日期:2006-06-01 00:00:00

  • Indacaterol/glycopyrronium: a dual bronchodilator for COPD.

    abstract::Indacaterol/glycopyrronium (IND/GLY) 110/50mcg was the first once-daily, long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combination (FDC) approved in Europe for the treatment of chronic obstructive pulmonary disease (COPD). Development of IND/GLY was driven by the need to improve the...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Banerji D,Fogel R,Patalano F

    更新日期:2018-01-01 00:00:00

  • Cancer cell senescence: a new frontier in drug development.

    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


    authors: Cairney CJ,Bilsland AE,Evans TR,Roffey J,Bennett DC,Narita M,Torrance CJ,Keith WN

    更新日期:2012-03-01 00:00:00

  • The power of combining phenotypic and target-focused drug discovery.

    abstract::A fierce dispute has arisen between the supporters of phenotypic and target-focused screening regarding which path grants the higher probability of successful drug development. A chance to reconcile these two approaches lies in successful target deconvolution (TD) after phenotypic screens. But, despite the panoply of ...

    journal_title:Drug discovery today

    pub_type: 杂志文章,评审


    authors: Heilker R,Lessel U,Bischoff D

    更新日期:2019-02-01 00:00:00