scholarly journals Bioengineering of Extracellular Vesicles: Exosome-Based Next-Generation Therapeutic Strategy in Cancer

2021 ◽  
Vol 8 (10) ◽  
pp. 139
Author(s):  
Priyanka Saha ◽  
Suchisnigdha Datta ◽  
Sukanya Ghosh ◽  
Anurima Samanta ◽  
Paramita Ghosh ◽  
...  
Keyword(s):  
Small Molecules ◽  
Therapeutic Strategy ◽  
Chemotherapeutic Drugs ◽  
Immune Modulators ◽  
Cancer Management ◽  
Promising Tool ◽  
Cargo Proteins ◽  
Anticancer Treatment ◽  
Intracellular Signal ◽  
Tumor Growth And Metastasis

Extracellular nano vesicles and exosomes hold compelling evidence in intercellular communication. Exosomal intracellular signal transduction is mediated by the transfer of cargo proteins, lipids, micro (mi)RNAs, long noncoding (lnc)RNAs, small interfering (si)RNAs, DNA, and other functional molecules that play a pivotal role in regulating tumor growth and metastasis. However, emerging research trends indicate that exosomes may be used as a promising tool in anticancer treatment. This review features a majority of the bioengineering applications of fabricated exosomal cargoes. It also encompasses how the manipulation and delivery of specific cargoes—noncoding RNAs (ncRNAs), recombinant proteins, immune-modulators, chemotherapeutic drugs, and other small molecules—may serve as a precise therapeutic approach in cancer management.

scholarly journals Bacteriophages as drivers of bacterial virulence and their potential for biotechnological exploitation

2020 ◽  
Author(s):  
Kaat Schroven ◽  
Abram Aertsen ◽  
Rob Lavigne
Keyword(s):  
Small Molecules ◽  
Bacterial Infections ◽  
Bacterial Virulence ◽  
Arms Race ◽  
Control Mechanisms ◽  
Human Pathogens ◽  
Vaccine Candidates ◽  
Cargo Proteins ◽  
Genes Encoding ◽  
Mutualistic Relationship

ABSTRACT Bacteria-infecting viruses (phages) and their hosts maintain an ancient and complex relationship. Bacterial predation by lytic phages drives an ongoing phage-host arms race, whereas temperate phages initiate mutualistic relationships with their hosts upon lysogenization as prophages. In human pathogens, these prophages impact bacterial virulence in distinct ways: by secretion of phage-encoded toxins, modulation of the bacterial envelope, mediation of bacterial infectivity and the control of bacterial cell regulation. This review builds the argument that virulence-influencing prophages hold extensive, unexplored potential for biotechnology. More specifically, it highlights the development potential of novel therapies against infectious diseases, to address the current antibiotic resistance crisis. First, designer bacteriophages may serve to deliver genes encoding cargo proteins which repress bacterial virulence. Secondly, one may develop small molecules mimicking phage-derived proteins targeting central regulators of bacterial virulence. Thirdly, bacteria equipped with phage-derived synthetic circuits which modulate key virulence factors could serve as vaccine candidates to prevent bacterial infections. The development and exploitation of such antibacterial strategies will depend on the discovery of other prophage-derived, virulence control mechanisms and, more generally, on the dissection of the mutualistic relationship between temperate phages and bacteria, as well as on continuing developments in the synthetic biology field.

scholarly journals Targeting Mitochondria as Therapeutic Strategy for Metabolic Disorders

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Daniela Sorriento ◽  
Antonietta Valeria Pascale ◽  
Rosa Finelli ◽  
Anna Lisa Carillo ◽  
Roberto Annunziata ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Mitochondrial Dysfunction ◽  
Small Molecules ◽  
Metabolic Disorders ◽  
Therapeutic Strategy ◽  
Cell Metabolism ◽  
Therapeutic Interventions ◽  
Mtdna Mutations ◽  
Pathological Conditions ◽  
Mitochondria Targeting

Mitochondria are critical regulator of cell metabolism; thus, mitochondrial dysfunction is associated with many metabolic disorders. Defects in oxidative phosphorylation, ROS production, or mtDNA mutations are the main causes of mitochondrial dysfunction in many pathological conditions such as IR/diabetes, metabolic syndrome, cardiovascular diseases, and cancer. Thus, targeting mitochondria has been proposed as therapeutic approach for these conditions, leading to the development of small molecules to be tested in the clinical scenario. Here we discuss therapeutic interventions to treat mitochondrial dysfunction associated with two major metabolic disorders, metabolic syndrome, and cancer. Finally, novel mechanisms of regulation of mitochondrial function are discussed, which open new scenarios for mitochondria targeting.

Protein degradation: a validated therapeutic strategy with exciting prospects

2017 ◽  
Vol 61 (5) ◽  
pp. 517-527 ◽  
Author(s):  
Honorine Lebraud ◽  
Tom D. Heightman
Keyword(s):  
Animal Models ◽  
Protein Degradation ◽  
Small Molecules ◽  
Cancer Patients ◽  
Clinical Efficacy ◽  
Therapeutic Strategy ◽  
Substrate Recognition ◽  
Pharmacological Targets ◽  
Preclinical Animal Models

In a time of unprecedented challenges in developing potent, selective and well-tolerated protein inhibitors as therapeutics, drug hunters are increasingly seeking alternative modalities to modulate pharmacological targets. Selective inhibitors are achievable for only a fraction of the proteome, and are not guaranteed to elicit the desired response in patients, especially when pursuing targets identified through genetic knockdown. Targeted protein degradation holds the potential to expand the range of proteins that can be effectively modulated. Drugs inducing protein degradation through misfolding or by modulating cereblon (CRBN) substrate recognition are already approved for treatment of cancer patients. The last decade has seen the development of proteolysis targeting chimeras (PROTACs), small molecules that elicit proteasomal degradation by causing protein polyubiquitination. These have been used to degrade a range of disease-relevant proteins in cells, and some show promising efficacy in preclinical animal models, although their clinical efficacy and tolerability is yet to be proven. This review introduces current strategies for protein degradation with an emphasis on PROTACs and the role of click chemistry in PROTAC research through the formation of libraries of preclicked PROTACs or in-cell click-formed PROTACs (CLIPTACs).

scholarly journals THE USE OF TOFACITINIB FOR TREATMENT PATIENTS WITH PSORIASIS IN CONDITIONS OF THE DERMATOLOGICAL HOSPITAL

2017 ◽  
Vol 20 (4) ◽  
pp. 220-226
Author(s):  
Ella V. Natarova ◽  
N. S Rudneva ◽  
M. S Kuklina ◽  
Ya. Yu Chumakova
Keyword(s):  
Signal Transduction ◽  
Psoriatic Arthritis ◽  
Small Molecules ◽  
Observational Studies ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Local Data ◽  
Janus Kinases ◽  
Short Course ◽  
Intracellular Signal

A growing understanding of the cellular and molecular mechanisms of inflammation in psoriasis and psoriatic arthritis opens the way to the treatment these diseases with the help of new small molecules, associated with the blockade of intracellular signal transduction. Jaqinus®/Xeljanz® (tofacitinib, “Pfizer”) is the first oral inhibitor of Janus kinases for the treatment of chronic moderately severe and severe plaque psoriasiswhich was approved for usage in Russia. The authors also present own local data regarding usage of tofacitinib 10 and 20 mg/day by short course for the treatment group of 13 patients with severe forms of plaque psoriasis in a progressing stage with resistance to prior systemic conventional therapy who were treated at the TDVCD. The efficacy of therapeutic strategies with the use of tofacitinib for patients of the dermatological hospital with the aim of improving and stabilizing of acute process is shown. Further prospective and observational studies to refine the dosing and safety profile of this group of drugs are needed.

scholarly journals Hypoxia Regulated Inhibin Promotes Tumor Growth and Vascular Permeability By ACVRL1 and CD105 Dependent VE-Cadherin Internalization

2021 ◽  
Author(s):  
Karthikeyan Mythreye ◽  
Ben Horst ◽  
Shrikant Pradhan ◽  
Roohi Chaudhary ◽  
Eduardo Listik ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Ovarian Cancer Cell ◽  
Vascular Normalization ◽  
Cancer Management ◽  
Vessel Normalization ◽  
Ovarian Cancer Cell Lines ◽  
Tumor Growth And Metastasis ◽  
Early Tumor

Abstract Hypoxia, a driver of tumor growth and metastasis, regulates angiogenic pathways that are targets for vessel normalization and ovarian cancer management. However, toxicities and resistance to anti-angiogenics limits their use making identification of new targets vital. Inhibin, a heteromeric TGFb ligand, is a contextual regulator of tumor progression acting as an early tumor suppressor, yet also an established biomarker for ovarian cancers. Here, we demonstrate a previously unknown role for inhibins and find that hypoxia increases inhibin levels in ovarian cancer cell lines, xenograft tumors, and patients. Inhibin is regulated specifically through HIF-1, shifting the balance from activins to inhibins. Hypoxia regulated inhibin promotes tumor growth, endothelial cell invasion and permeability. Targeting inhibin in vivo through knockdown and anti-inhibin strategies robustly reduces permeability in vivo and alters the balance of pro and anti-angiogenic mechanisms resulting in vascular normalization. Mechanistically, inhibin regulates permeability by increasing VE-cadherin internalization via ACVRL1 and CD105, a receptor complex that we find stabilized directly by inhibin. Our findings are the first to demonstrate direct roles for inhibins in vascular normalization via TGF-b receptors providing new insights into the therapeutic significance of inhibins as a strategy to normalize the tumor vasculature in ovarian cancer.

Small Molecules Targeting Mutant P53: A Promising Approach for Cancer Treatment

2020 ◽  
Vol 26 (41) ◽  
pp. 7323-7336 ◽  
Author(s):  
Elizabeth A. Lopes ◽  
Sara Gomes ◽  
Lucília Saraiva ◽  
Maria M.M. Santos
Keyword(s):  
Clinical Trials ◽  
Small Molecules ◽  
Poor Prognosis ◽  
Therapeutic Strategy ◽  
Colorectal Cancers ◽  
Mutant P53 ◽  
P53 Mutations ◽  
Wild Type ◽  
Tumor Types ◽  
Mutant Forms

: More than half of all human tumors express mutant forms of p53, with the ovary, lung, pancreas, and colorectal cancers among the tumor types that display the highest prevalence of p53 mutations. In addition, the expression of mutant forms of p53 in tumors is associated with poor prognosis due to increased chemoresistance and invasiveness. Therefore, the pharmacological restoration of wild-type-like activity to mutant p53 arises as a promising therapeutic strategy against cancer. This review is focused on the most relevant mutant p53 small molecule reactivators described to date. Despite some of them have entered into clinical trials, none has reached the clinic, which emphasizes that new pharmacological alternatives, particularly with higher selectivity and lower adverse toxic side effects, are still required.

scholarly journals MicroRNAs in Cancer Management: Big Challenges for Small Molecules

2015 ◽  
Vol 2015 ◽  
pp. 1-2 ◽  
Author(s):  
Paolo Gandellini ◽  
Elisa Giovannetti ◽  
Francesco Nicassio
Keyword(s):  
Small Molecules ◽  
Cancer Management

Targeting the IAP Family of Caspase Inhibitors as an Emerging Therapeutic Strategy

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 215-219 ◽  
Author(s):  
Aaron D. Schimmer ◽  
Shadi Dalili
Keyword(s):  
Small Molecules ◽  
Antisense Oligonucleotides ◽  
Poor Prognosis ◽  
Therapeutic Strategy ◽  
Hematologic Malignancies ◽  
Clinical Development ◽  
Inhibitor Of Apoptosis ◽  
Caspase Inhibitors ◽  
Execution Phase ◽  
Apoptosis Proteins

The IAPs (inhibitor of apoptosis proteins) are a family of caspase inhibitors that block the execution phase of apoptosis. Overexpression of IAPs confers chemoresistance and, in some groups of patients, is associated with a poor prognosis. Given their role in the development and progression of solid tumors and hematologic malignancies, efforts are underway to develop therapeutic IAP inhibitors, with a focus on X-linked IAP (XIAP) and survivin. Antisense oligonucleotides that target XIAP and survivin have been developed and are currently in phase I clinical trial. Small-molecules that bind and inhibit XIAP have also been identified and are in the process of clinical development. This review focuses on the preclinical data that support the development of IAP-targeted therapies.

Sign in / Sign up

Export Citation Format

Share Document