FREQUENT HOMOLOGOUS RECOMBINATION DEFICIENCY IN HIGH-GRADE ENDOMETRIAL CANCER PROVIDES OPPORTUNITIES FOR NOVEL THERAPEUTIC STRATEGIES.

2017 ◽  
Author(s):  
Marthe de Jonge
Keyword(s):  
Endometrial Cancer ◽  
Homologous Recombination ◽  
Therapeutic Strategies ◽  
High Grade ◽  
Homologous Recombination Deficiency ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

scholarly journals Biological intratumoral therapy for the high-grade glioma part I: intratumoral delivery and immunotoxins

CNS Oncology ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. CNS38 ◽  
Author(s):  
Joshua Loya ◽  
Charlie Zhang ◽  
Emily Cox ◽  
Achal S Achrol ◽  
Santosh Kesari
Keyword(s):  
Translational Research ◽  
Standard Of Care ◽  
High Grade Glioma ◽  
Therapeutic Strategies ◽  
High Grade ◽  
Major Focus ◽  
Microsurgical Resection ◽  
Intratumoral Delivery ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Management of high-grade gliomas remains a complex challenge. Standard of care consists of microsurgical resection, chemotherapy and radiation, but despite these aggressive multimodality therapies the overall prognosis remains poor. A major focus of ongoing translational research studies is to develop novel therapeutic strategies that can maximize tumor cell eradication while minimizing collateral side effects. Particularly, biological intratumoral therapies have been the focus of new translational research efforts due to their inherent potential to be both dynamically adaptive and target specific. This two-part review will provide an overview of biological intratumoral therapies and summarize key advances and remaining challenges in intratumoral biological therapies for high-grade glioma. Part I focuses on discussion of the concepts of intratumoral delivery and immunotoxin therapies.

scholarly journals Endometrial Cancer as a Metabolic Disease with Dysregulated PI3K Signaling: Shedding Light on Novel Therapeutic Strategies

2020 ◽  
Vol 21 (17) ◽  
pp. 6073
Author(s):  
Satoru Kyo ◽  
Kentaro Nakayama
Keyword(s):  
Endometrial Cancer ◽  
Epidemiological Studies ◽  
Reproductive Organs ◽  
Pi3k Pathway ◽  
Therapeutic Strategies ◽  
Pi3k Signaling ◽  
Obese Women ◽  
Alternative Pathways ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Endometrial cancer (EC) is one of the most common malignancies of the female reproductive organs. The most characteristic feature of EC is the frequent association with metabolic disorders. However, the components of these disorders that are involved in carcinogenesis remain unclear. Accumulating epidemiological studies have clearly revealed that hyperinsulinemia, which accompanies these disorders, plays central roles in the development of EC via the insulin-phosphoinositide 3 kinase (PI3K) signaling pathway as a metabolic driver. Recent comprehensive genomic analyses showed that over 90% of ECs have genomic alterations in this pathway, resulting in enhanced insulin signaling and production of optimal tumor microenvironments (TMEs). Targeting PI3K signaling is therefore an attractive treatment strategy. Several clinical trials for recurrent or advanced ECs have been attempted using PI3K-serine/threonine kinase (AKT) inhibitors. However, these agents exhibited far lower efficacy than expected, possibly due to activation of alternative pathways that compensate for the PIK3-AKT pathway and allow tumor growth, or due to adaptive mechanisms including the insulin feedback pathway that limits the efficacy of agents. Overcoming these responses with careful management of insulin levels is key to successful treatment. Further interest in specific TMEs via the insulin PI3K-pathway in obese women will provide insight into not only novel therapeutic strategies but also preventive strategies against EC.

scholarly journals The Current Landscape of Oncolytic Herpes Simplex Viruses as Novel Therapies for Brain Malignancies

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1158
Author(s):  
Joshua D. Bernstock ◽  
Samantha E. Hoffman ◽  
Jason A. Chen ◽  
Saksham Gupta ◽  
Ari D. Kappel ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Brain Tumors ◽  
Therapeutic Strategies ◽  
High Grade ◽  
Novel Therapies ◽  
Herpes Viruses ◽  
Significant Morbidity ◽  
Herpes Simplex Viruses ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Despite advances in surgical resection and chemoradiation, high-grade brain tumors continue to be associated with significant morbidity/mortality. Novel therapeutic strategies and approaches are, therefore, desperately needed for patients and their families. Given the success experienced in treating multiple other forms of cancer, immunotherapy and, in particular, immunovirotherapy are at the forefront amongst novel therapeutic strategies that are currently under investigation for incurable brain tumors. Accordingly, herein, we provide a focused mini review of pertinent oncolytic herpes viruses (oHSV) that are being investigated in clinical trials.

PCSK9 Inhibitors: Novel Therapeutic Strategies for Lowering LDLCholesterol

2018 ◽  
Vol 19 (2) ◽  
pp. 165-176 ◽  
Author(s):  
Yan Wang ◽  
Zhao-Peng Liu
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Maximum Tolerated Dose ◽  
Therapeutic Strategies ◽  
Low Density ◽  
Pcsk9 Inhibitors ◽  
Cvd Risk ◽  
Safety Issues ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Statins are currently the major therapeutic strategies to lower low-density lipoprotein cholesterol (LDL-C) levels. However, a number of hypercholesterolemia patients still have a residual cardiovascular disease (CVD) risk despite taking the maximum-tolerated dose of statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein receptor (LDLR), inducing its degradation in the lysosome and inhibiting LDLR recirculating to the cell membranes. The gain-offunction mutations in PCSK9 elevate the LDL-C levels in plasma. Therefore, PCSK9 inhibitors become novel therapeutic approaches in the treatment of hypercholesterolemia. Several PCSK9 inhibitors have been under investigation, and much progress has been made in clinical trials, especially for monoclonal antibodies (MoAbs). Two MoAbs, evolocumab and alirocumab, are now in clinical use. In this review, we summarize the development of PCSK9 inhibitors, including antisense oligonucleotides (ASOs), small interfering RNA (siRNA), small molecule inhibitor, MoAbs, mimetic peptides and adnectins, and the related safety issues.

scholarly journals The Senescence-Associated Secretory Phenotype (SASP) in the Challenging Future of Cancer Therapy and Age-Related Diseases

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 485
Author(s):  
Lorenzo Cuollo ◽  
Fabrizio Antonangeli ◽  
Angela Santoni ◽  
Alessandra Soriani
Keyword(s):  
Cancer Therapy ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Senescent Cell ◽  
Pharmacological Intervention ◽  
Tissue Microenvironment ◽  
Age Related ◽  
Secretory Phenotype ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Cellular senescence represents a robust tumor-protecting mechanism that halts the proliferation of stressed or premalignant cells. However, this state of stable proliferative arrest is accompanied by the Senescence-Associated Secretory Phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment and contributes to age-related conditions, including, paradoxically, cancer. Novel therapeutic strategies aim at eliminating senescent cells with the use of senolytics or abolishing the SASP without killing the senescent cell with the use of the so-called “senomorphics”. In addition, recent works demonstrate the possibility of modifying the composition of the secretome by genetic or pharmacological intervention. The purpose is not to renounce the potent immunostimulatory nature of SASP, but rather learning to modulate it for combating cancer and other age-related diseases. This review describes the main molecular mechanisms regulating the SASP and reports the evidence of the feasibility of abrogating or modulating the SASP, discussing the possible implications of both strategies.

scholarly journals Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management

2021 ◽  
Vol 139 ◽  
pp. 111708
Author(s):  
Pushkar Singh Rawat ◽  
Aiswarya Jaiswal ◽  
Amit Khurana ◽  
Jasvinder Singh Bhatti ◽  
Umashanker Navik
Keyword(s):  
Molecular Mechanism ◽  
Therapeutic Strategies ◽  
Effective Management ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

scholarly journals Short-Term Reproducibility of MUC5AC Measurement in Human Tear Fluid

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 57
Author(s):  
Ashley M. Woodward ◽  
Michelle Senchyna ◽  
Pablo Argüeso
Keyword(s):  
Statistical Difference ◽  
Tear Film ◽  
Therapeutic Strategies ◽  
Individual Variability ◽  
Tear Fluid ◽  
Individual Data ◽  
Short Term ◽  
Coefficients Of Variation ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

The assessment of tear fluid components is a common and valuable approach to understanding ocular surface disease and testing the efficacy of novel therapeutic strategies. However, the interpretation and utility of the findings can be limited by changes in the composition of the tear film, particularly in studies requiring repetitive patient sampling. Here, tear samples were collected twice within a one-hour interval to evaluate the short-term reproducibility of an immunoassay aimed to measure the amount of MUC5AC mucin. We found no statistical difference in total protein or MUC5AC content between the two consecutive collections of tear fluid, although the inter-individual variability in each group was high, with coefficients of variation exceeding 30% and 50%, respectively. Scatterplots showed a significant correlation in both protein and MUC5AC following collection within a one-hour interval. These data indicate that, regardless of the high inter-individual variability, repeated collection of tear fluid within an hour interval produces reproducible intra-individual data in terms of MUC5AC mucin content, and suggest that the normal mucin composition of the tear fluid can be re-established within an hour of the initial collection.

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