Targeted Nanomedicine for Cancer Therapeutics: Towards Precision Medicine Overcoming Drug Resistance
Intrinsic anticancer drug resistance which presents prior to chemotherapy as well as acquired resistance due to drug treatment, remain the dominant impediments towards curative cancer therapy. Hence, novel targeted strategies to overcome cancer multidrug resistance (MDR) constitute a key aim of cancer research. In this respect, targeted nanomedicine offers innovative therapeutic strategies to overcome the various limitations of conventional chemotherapy, enabling enhanced selectivity, early and more precise cancer diagnosis, individualized treatment as well as overcoming of MDR. (Source: Drug Resistance Updates)
Source: Drug Resistance Updates - May 21, 2017 Category: Drugs & Pharmacology Authors: Maya Bar-Zeev, Yoav D. Livney, Yehuda G. Assaraf Source Type: research
New strategies for targeting and treatment of multi-drug resistant Staphylococcus aureus
Staphylococcus aureus is a major cause of bacterial infection in humans, and has been notoriously able to acquire resistance to a variety of antibiotics. An example is methicillin-resistant S. aureus (MRSA), which despite having been initially associated with clinical settings, now is one of the key causative agents of community-acquired infections. Antibiotic resistance in S. aureus involves mechanisms ranging from drug efflux to increased expression or mutation of target proteins, and this has required innovative approaches to develop novel treatment methodologies. (Source: Drug Resistance Updates)
Source: Drug Resistance Updates - April 6, 2017 Category: Drugs & Pharmacology Authors: L. Mayrink Assis, M. Nedeljkovi ć, A. Dessen Source Type: research
Drug-biomarker co-development in oncology – 20 years and counting
Predictive biomarkers for oncology are necessary to accurately identify patients who will benefit from anticancer treatment. Recently approved oncology drugs target discrete molecular aberrations or pathways in tumor cells and consequently are active on a subset of patient population, yet clinical studies have shown that not all biomarker-positive patients respond. The advancement of predictive biomarkers needs to detect novel and evolving drug resistance mechanisms, not only to guide the selection of patient subsets for specific treatments, but to identify new therapeutic targets. (Source: Drug Resistance Updates)
Source: Drug Resistance Updates - February 20, 2017 Category: Drugs & Pharmacology Authors: Julianne D. Twomey, Nina N. Brahme, Baolin Zhang Source Type: research
Drug-Biomarker Co-development in Oncology - 20 Years and Counting
Predictive biomarkers for oncology are necessary to accurately identify patients who will benefit from anticancer treatment. Recently approved oncology drugs target discrete molecular aberrations or pathways in tumor cells and consequently are active on a subset of patient population, yet clinical studies have shown that not all biomarker-positive patients respond. The advancement of predictive biomarkers needs to detect novel and evolving drug resistance mechanisms, not only to guide the selection of patient subsets for specific treatments, but to identify new therapeutic targets. (Source: Drug Resistance Updates)
Source: Drug Resistance Updates - February 20, 2017 Category: Drugs & Pharmacology Authors: Julianne D. Twomey, Nina N. Brahme, Baolin Zhang Source Type: research
Corrigendum to “The reduced concentration of citrate in cancer cells: An indicator of cancer aggressiveness and a possible therapeutic target” [Drug Resistance Updates 29 (2016) 47–53]
The authors regret that the first name and last name were published in correctly in the original version and this has now been corrected. The authors would like to apologise for any inconvenience caused. (Source: Drug Resistance Updates)
Source: Drug Resistance Updates - February 7, 2017 Category: Drugs & Pharmacology Authors: Philippe Icard, Hubert Lincet Tags: Corrigendum Source Type: research
Novel immune check point inhibiting antibodies in cancer therapy —Opportunities and challenges
Drug resistance of tumor cells to chemotherapy is limiting the therapeutic efficacy of most anticancer drugs and represents a major obstacle in medical oncology. However, treatment of various human malignancies with biologics, mostly monoclonal antibodies (mAbs), is not limited by such chemoresistance mechanisms. However, other resistance or evasion mechanisms limit the efficacy to anticancer therapeutic mAbs that engage tumor-associated antigens on the surface of the malignant cells. Immune checkpoint blocking monoclonal antibodies are heralded as a promising therapeutic approach in clinical oncology. (Source: Drug Resistance Updates)
Source: Drug Resistance Updates - February 3, 2017 Category: Drugs & Pharmacology Authors: Yael Diesendruck, Itai Benhar Source Type: research
The Importance of Breast Cancer Resistance Protein to the Kidneys Excretory Function and Chemotherapeutic Resistance
The relevance of membrane transporters gained momentum in recent years and it is now widely recognized that transporters are key players in drug disposition and chemoresistance. As such, the kidneys harbor a variety of drug transporters and are one of the main routes for xenobiotic excretion. The breast cancer resistance protein (BCRP/ABCG2) is widely accepted as a key mediator of anticancer drug resistance and is a prominent renal drug transporter. Here, we review the role of BCRP in both processes and present a multitude of variables that can influence its activity. (Source: Drug Resistance Updates)
Source: Drug Resistance Updates - January 12, 2017 Category: Drugs & Pharmacology Authors: Pedro Caetano-Pinto, Jitske Jansen, Yehuda G. Assaraf, Rosalinde Masereeuw Tags: Invited review Source Type: research
Inverse Correlation Between the Metastasis Suppressor RKIP and the Metastasis Inducer YY1: Contrasting Roles in the Regulation of Chemo/Immuno-Resistance in Cancer
Several gene products have been postulated to mediate inherent and/or acquired anticancer drug resistance and tumor metastasis. Among these, the metastasis suppressor and chemo-immuno-sensitizing gene product, Raf Kinase Inhibitor Protein (RKIP), is poorly expressed in many cancers. In contrast, the metastasis inducer and chemo-immuno-resistant factor Yin Yang 1 (YY1) is overexpressed in many cancers. This inverse relationship between RKIP and YY1 expression suggests that these two gene products may be regulated via cross-talks of molecular signaling pathways, culminating in the expression of different phenotypes based on ...
Source: Drug Resistance Updates - January 8, 2017 Category: Drugs & Pharmacology Authors: Stephanie Wottrich, Samantha Kaufhold, Emmanuel Chrysos, Odysseas Zoras, Stavroula Baritaki, Benjamin Bonavida Source Type: research
Editorial Board
(Source: Drug Resistance Updates)
Source: Drug Resistance Updates - January 1, 2017 Category: Drugs & Pharmacology Source Type: research
Active efflux in dormant bacterial cells – new insights into antibiotic persistence
Bacterial persisters are phenotypic variants of an isogenic cell population that can survive antibiotic treatment and resume growth after the antibiotics have been removed. Cell dormancy has long been considered the principle mechanism underlying persister formation. However, dormancy alone is insufficient to explain the full range of bacterial persistence. Our recent work revealed that in addition to ‘passive defense’ via dormancy, persister cells employ ‘active defense’ via enhanced efflux activity to expel drugs. (Source: Drug Resistance Updates)
Source: Drug Resistance Updates - November 28, 2016 Category: Drugs & Pharmacology Authors: Yingying Pu, Yuehua Ke, Fan Bai Source Type: research
Sensitizing pathogens to antibiotics using the CRISPR-Cas system
The extensive use of antibiotics over the last century has resulted in a significant artificial selection pressure for antibiotic-resistant pathogens to evolve. Various strategies to fight these pathogens have been introduced including new antibiotics, naturally-derived enzymes/peptides that specifically target pathogens and bacteriophages that lyse these pathogens. A new tool has recently been introduced in the fight against drug-resistant pathogens − the prokaryotic defense mechanism − clustered regularly interspaced short palindromic repeats-CRISPR associated (CRISPR-Cas) system. (Source: Drug Resistance Updates)
Source: Drug Resistance Updates - November 25, 2016 Category: Drugs & Pharmacology Authors: Moran Goren, Ido Yosef, Udi Qimron Source Type: research
New insights and evolving role of pegylated liposomal doxorubicin in cancer therapy
We herein review various pharmacological and clinical aspects of pegylated liposomal doxorubicin (PLD), the first nanomedicine to be approved for cancer therapy, and discuss the gap between its potent antitumor activity in preclinical studies and its comparatively modest achievements in clinical studies and limited use in clinical practice. PLD is a complex formulation of doxorubicin based on pharmaceutical nanotechnology with unique pharmacokinetic and pharmacodynamic properties. Its long circulation time with stable retention of the payload and its accumulation in tumors with high vascular permeability both result in imp...
Source: Drug Resistance Updates - October 27, 2016 Category: Drugs & Pharmacology Authors: Alberto A. Gabizon, Yogita Patil, Ninh M. La-Beck Source Type: research
Molecular mechanisms and clinical implications of bacterial persistence
Any bacterial population harbors a small number of phenotypic variants that survive exposure to high concentrations of antibiotic. Importantly, these so-called ‘persister cells’ compromise successful antibiotic therapy of bacterial infections and are thought to contribute to the development of antibiotic resistance. Intriguingly, drug-tolerant persisters have also been identified as a factor underlying failure of chemotherapy in tumor cell populations. Recent studies have begun to unravel the complex molecular mechanisms underlying persister formation and revolve around stress responses and toxin-antitoxin modules. (So...
Source: Drug Resistance Updates - October 13, 2016 Category: Drugs & Pharmacology Authors: Joran Elie Michiels, Bram Van den Bergh, Natalie Verstraeten, Jan Michiels Source Type: research
Heparanase: from basic research to therapeutic applications in cancer and inflammation
Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Heparanase expression is enhanced in almost all cancers examined including various carcinomas, sarcomas and hematological malignancies. Numerous clinical association studies have consistently demonstrated that upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. (Source: Drug Resistance Updates)
Source: Drug Resistance Updates - October 5, 2016 Category: Drugs & Pharmacology Authors: Israel Vlodavsky, Preeti Singh, Ilanit Boyango, Lilach Gutter-Kapon, Michael Elkin, Ralph D. Sanderson, Neta Ilan Source Type: research
The reduced concentration of citrate in cancer cells: an indicator of cancer aggressiveness and a possible therapeutic target
Proliferating cells reduce their oxidative metabolism and rely more on glycolysis, even in the presence of O2 (Warburg effect). This shift in metabolism reduces citrate biosynthesis and diminishes intracellular acidity, both of which promote glycolysis sustaining tumor growth. Because citrate is the donor of acetyl-CoA, its reduced production favors a deacetylation state of proteins favoring resistance to apoptosis and epigenetic changes, both processes contributing to tumor aggressiveness. Citrate levels could be monitored as an indicator of cancer aggressiveness (as already shown in human prostate cancer) and/or could se...
Source: Drug Resistance Updates - September 20, 2016 Category: Drugs & Pharmacology Authors: Icard Philippe, Lincet Hubert Source Type: research
