Targeting Mutant KRAS for Anticancer Therapy

2019 ◽  
Vol 19 (23) ◽  
pp. 2098-2113 ◽  
Author(s):  
Fengqian Chen ◽  
Martin P. Alphonse ◽  
Yan Liu ◽  
Qi Liu
Keyword(s):  
Future Development ◽  
Anticancer Therapy ◽  
Therapeutic Strategies ◽  
Therapeutic Approaches ◽  
Cellular Processes ◽  
The Past ◽  
Cancer Types

: Over the past decades, designing therapeutic strategies to target KRAS-mutant cancers, which is one of the most frequent mutant oncogenes among all cancer types, have proven unsuccessful regardless of many concerted attempts. There are key challenges for KRAS-mutant anticancer therapy, as the complex cellular processes involved in KRAS signaling has present. Herein, we highlight the emerging therapeutic approaches for inhibiting KRAS signaling and blocking KRAS functions, in hope to serve as a more effective guideline for future development of therapeutics.

scholarly journals Molecular Mechanisms of Heat Shock Factors in Cancer

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1202
Author(s):  
Mikael Christer Puustinen ◽  
Lea Sistonen
Keyword(s):  
Heat Shock ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Heat Shock Factors ◽  
Therapeutic Approaches ◽  
The Past ◽  
Cancer Types ◽  
Cellular Pathways ◽  
As Stress ◽  
Regulatory Functions

Malignant transformation is accompanied by alterations in the key cellular pathways that regulate development, metabolism, proliferation and motility as well as stress resilience. The members of the transcription factor family, called heat shock factors (HSFs), have been shown to play important roles in all of these biological processes, and in the past decade it has become evident that their activities are rewired during tumorigenesis. This review focuses on the expression patterns and functions of HSF1, HSF2, and HSF4 in specific cancer types, highlighting the mechanisms by which the regulatory functions of these transcription factors are modulated. Recently developed therapeutic approaches that target HSFs are also discussed.

scholarly journals The Potential of MicroRNAs in Personalized Medicine against Cancers

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Anne Saumet ◽  
Anthony Mathelier ◽  
Charles-Henri Lecellier
Keyword(s):  
Personalized Medicine ◽  
Human Cancer ◽  
Therapeutic Strategies ◽  
Cellular Processes ◽  
Cancer Types

MicroRNAs orchestrate the expression of the genome and impact many, if not all, cellular processes. Their deregulation is thus often causative of human malignancies, including cancers. Numerous studies have implicated microRNAs in the different steps of tumorigenesis including initiation, progression, metastasis, and resistance to chemo/radiotherapies. Thus, microRNAs constitute appealing targets for novel anticancer therapeutic strategies aimed at restoring their expression or function. As microRNAs are present in a variety of human cancer types, microRNA profiles can be used as tumor-specific signatures to detect various cancers (diagnosis), to predict their outcome (prognosis), and to monitor their treatment (theranosis). In this review, we present the different aspects of microRNA biology that make them remarkable molecules in the emerging field of personalized medicine against cancers and provide several examples of their industrial exploitation.

scholarly journals Novel therapeutic approaches for chronic kidney disease due to glomerular disorders

2016 ◽  
Vol 311 (1) ◽  
pp. F63-F65 ◽  
Author(s):  
Maria Del Nogal-Avila ◽  
Hector Donoro-Blazquez ◽  
Manish K. Saha ◽  
Caroline B. Marshall ◽  
Lionel C. Clement ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Trials ◽  
Kidney Disease ◽  
Therapeutic Strategies ◽  
Therapeutic Approaches ◽  
The Past ◽  
Disease Mechanisms ◽  
Toxic Drugs ◽  
Novel Therapeutic

Improved understanding of glomerular disease mechanisms over the past decade has led to the emergence of new and targeted therapeutic strategies for chronic kidney disease (CKD). Most promising among these are the administration of recombinant mutated human angiopoietin-like 4, sialic acid-related sugars that induce sialylation in vivo, compounds related to Bis-T-23, and immune depletion of the soluble urokinase receptor from the circulation. Taking these therapeutic strategies into clinical trials will be the first step away from repurposed and relatively toxic drugs currently used for treating kidney disease.

scholarly journals Fecal microRNAs as Innovative Biomarkers of Intestinal Diseases and Effective Players in Host-Microbiome Interactions

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2174 ◽  
Author(s):  
Meysam Sarshar ◽  
Daniela Scribano ◽  
Cecilia Ambrosi ◽  
Anna Teresa Palamara ◽  
Andrea Masotti
Keyword(s):  
Colorectal Cancer ◽  
Target Genes ◽  
Disease Diagnosis ◽  
Bacterial Metabolism ◽  
Therapeutic Approaches ◽  
Intestinal Diseases ◽  
Cellular Processes ◽  
The Past ◽  
Messenger Molecules

Over the past decade, short non-coding microRNAs (miRNAs), including circulating and fecal miRNAs have emerged as important modulators of various cellular processes by regulating the expression of target genes. Recent studies revealed the role of miRNAs as powerful biomarkers in disease diagnosis and for the development of innovative therapeutic applications in several human conditions, including intestinal diseases. In this review, we explored the literature and summarized the role of identified dysregulated fecal miRNAs in intestinal diseases, with particular focus on colorectal cancer (CRC) and celiac disease (CD). The aim of this review is to highlight one fascinating aspect of fecal miRNA function related to gut microbiota shaping and bacterial metabolism influencing. The role of miRNAs as “messenger” molecules for inter kingdom communications will be analyzed to highlight their role in the complex host-bacteria interactions. Moreover, whether fecal miRNAs could open up new perspectives to develop novel suitable biomarkers for disease detection and innovative therapeutic approaches to restore microbiota balance will be discussed.

scholarly journals Cholesterol and Sphingolipid Enriched Lipid Rafts as Therapeutic Targets in Cancer

2021 ◽  
Vol 22 (2) ◽  
pp. 726
Author(s):  
Michela Codini ◽  
Mercedes Garcia-Gil ◽  
Elisabetta Albi
Keyword(s):  
Lipid Rafts ◽  
Cholesterol Content ◽  
Membrane Lipid ◽  
Therapeutic Strategies ◽  
Membrane Properties ◽  
Cellular Processes ◽  
The Past ◽  
Nuclear Membranes ◽  
Technical Advances

Lipid rafts are critical cell membrane lipid platforms enriched in sphingolipid and cholesterol content involved in diverse cellular processes. They have been proposed to influence membrane properties and to accommodate receptors within themselves by facilitating their interaction with ligands. Over the past decade, technical advances have improved our understanding of lipid rafts as bioactive structures. In this review, we will cover the more recent findings about cholesterol, sphingolipids and lipid rafts located in cellular and nuclear membranes in cancer. Collectively, the data provide insights on the role of lipid rafts as biomolecular targets in cancer with good perspectives for the development of innovative therapeutic strategies.

scholarly journals Evaluation of MicroRNAs Regulating Anoikis Pathways and Its Therapeutic Potential

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Sharan Malagobadan ◽  
Noor Hasima Nagoor
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Therapeutic Potential ◽  
Research Question ◽  
Therapeutic Strategies ◽  
Anoikis Resistance ◽  
The Past ◽  
Cancer Types ◽  
Novel Therapeutic Strategies ◽  
Survival Mechanisms

Dysregulation of microRNAs (miRNAs) has been implicated in almost every known survival mechanisms utilized by cancer cells. One of such mechanisms, anoikis resistance, plays a pivotal role in enabling metastasis by allowing cancer cells to circumvent cell death induced by lack of attachment. Understanding how miRNAs regulate the various anoikis pathways has become the research question of increasing number of studies published in the past years. Through these studies, a growing list of miRNAs has been identified to be important players in promoting either anoikis or resistance to anoikis. In this review, we will be focusing on these miRNAs and how the findings from those studies can contribute to novel therapeutic strategies against cancer progression. We will be examining miRNAs that have been found to promote anoikis sensitivity in numerous cancer types followed by miRNAs that inhibit anoikis. In addition, we will also be taking a look at major signaling pathways involved in the action of the each of these miRNAs to gain a better understanding on how miRNAs regulate anoikis.

Changes in the Teacher Training and Qualification in Bulgaria

2019 ◽  
Vol 7 (3) ◽  
pp. 3-23
Author(s):  
Viara Gyurova
Keyword(s):  
Teacher Education ◽  
Teacher Training ◽  
20Th Century ◽  
Future Development ◽  
Training System ◽  
Development System ◽  
The Past ◽  
Teacher Qualification

Since the beginning of the last decade of the past 20th century, Bulgaria has entered a new, complex stage of its development, with many reforms. Education and teacher training reforms are influenced by the global and European trends, as well as by the national changes (political, economical, social, and technological). The author analyses the main characteristics of the changed teacher training system and teacher qualification and development system. Some of the challenges and directions of the transformation and future development of the teacher education and qualification in Bulgaria are discussed.

Targeting Membrane Receptors of Ovarian Cancer Cells for Therapy

2019 ◽  
Vol 19 (6) ◽  
pp. 449-467
Author(s):  
Zhiquan Liang ◽  
Ziwen Lu ◽  
Yafei Zhang ◽  
Dongsheng Shang ◽  
Ruyan Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Receptor Binding ◽  
Cytoreductive Surgery ◽  
Therapeutic Strategies ◽  
Membrane Receptors ◽  
Ovarian Cancer Cells ◽  
Advanced Stage ◽  
Targeted Therapeutics ◽  
Cellular Processes

Ovarian cancer is a leading cause of death worldwide from gynecological malignancies, mainly because there are few early symptoms and the disease is generally diagnosed at an advanced stage. In addition, despite the effectiveness of cytoreductive surgery for ovarian cancer and the high response rates to chemotherapy, survival has improved little over the last 20 years. The management of patients with ovarian cancer also remains similar despite studies showing striking differences and heterogeneity among different subtypes. It is therefore clear that novel targeted therapeutics are urgently needed to improve clinical outcomes for ovarian cancer. To that end, several membrane receptors associated with pivotal cellular processes and often aberrantly overexpressed in ovarian cancer cells have emerged as potential targets for receptor-mediated therapeutic strategies including specific agents and multifunctional delivery systems based on ligand-receptor binding. This review focuses on the profiles and potentials of such strategies proposed for ovarian cancer treatment and imaging.

scholarly journals Translating Molecular Profiling of Soft Tissue Sarcomas into Daily Clinical Practice

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 512
Author(s):  
Celine Jacobs ◽  
Lore Lapeire
Keyword(s):  
Soft Tissue ◽  
Unmet Need ◽  
Soft Tissue Sarcomas ◽  
Molecular Profiling ◽  
Point Of View ◽  
Molecular Techniques ◽  
Mesenchymal Tumors ◽  
The Past ◽  
Cancer Types ◽  
Sarcoma Treatment

Soft tissue sarcomas are a group of rare mesenchymal tumors with more than 70 subtypes described. Treatment of these subtypes in an advanced setting is mainly according to a one-size-fits-all strategy indicating a high unmet need of new and more targeted therapeutic options in order to optimize survival. The introduction of advanced molecular techniques in cancer has led to better diagnostics and identification of new therapeutic targets, leading to more personalized treatment and improved prognosis for several cancer types. In sarcoma, a likewise evolution is seen, albeit at a slower pace. This manuscript describes how in the past years advanced molecular profiling in soft tissue sarcomas was able to identify specific and often pathognomonic aberrations, deferring standard sarcoma treatment in favor of more targeted treatment from an oncologist’s point of view.

scholarly journals Novel Roles for the Sirtuin Deacylase SIRT5 in Normal Physiology and in Cancer

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 741-741
Author(s):  
David Lombard
Keyword(s):  
Mitochondrial Matrix ◽  
Genomic Integrity ◽  
Biological Functions ◽  
Protein Targets ◽  
Post Translational Modifications ◽  
Catalytic Activities ◽  
Cellular Processes ◽  
Specific Cancer ◽  
Cancer Types ◽  
Chromatin Biology

Abstract Sirtuins are NAD+-dependent deacylases that regulate diverse cellular processes such as metabolic homeostasis and genomic integrity. Mammals possess seven sirtuin family members, SIRT1-SIRT7, that display diverse subcellular localization patterns, catalytic activities, protein targets, and biological functions. Three sirtuins, SIRT3, SIRT4, and SIRT5, are primarily located in the mitochondrial matrix. SIRT5 is a very inefficient deacetylase, instead removing negatively charged post-translational modifications (succinyl, glutaryl, and malonyl groups) from lysines of its target proteins, in mitochondria and throughout the cell. SIRT5 plays only modest known roles in normal physiology, with its major functions occurring in the heart under stress conditions. In contrast, in specific cancer types, including melanoma, we have identified a major pro-survival role for SIRT5. We have traced this function of SIRT5 to novel roles for this protein in regulating chromatin biology. New insights into mechanisms of SIRT5 action in cancer, and in normal myocardium, will be discussed.

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