scholarly journals CRISPR-dCas9-Based Artificial Transcription Factors to Improve Efficacy of Cancer Treatment With Drug Repurposing: Proposal for Future Research

2021 ◽  
Vol 10 ◽  
Author(s):  
Alejandro Martinez-Escobar ◽  
Benjamín Luna-Callejas ◽  
Eva Ramón-Gallegos
Keyword(s):  
Transcription Factors ◽  
Cancer Treatment ◽  
Drug Repurposing ◽  
Resistance Mechanisms ◽  
Cancer Drug ◽  
Future Research ◽  
Cancer Therapies ◽  
Advantages And Disadvantages ◽  
Artificial Transcription Factors ◽  
Repurposed Drugs

Due to the high resistance that cancer has shown to conventional therapies, it is difficult to treat this disease, particularly in advanced stages. In recent decades, treatments have been improved, being more specific according to the characteristics of the tumor, becoming more effective, less toxic, and invasive. Cancer can be treated by the combination of surgery, radiation therapy, and/or drug administration, but therapies based on anticancer drugs are the main cancer treatment. Cancer drug development requires long-time preclinical and clinical studies and is not cost-effective. Drug repurposing is an alternative for cancer therapies development since it is faster, safer, easier, cheaper, and repurposed drugs do not have serious side effects. However, cancer is a complex, heterogeneous, and highly dynamic disease with multiple evolving molecular constituents. This tumor heterogeneity causes several resistance mechanisms in cancer therapies, mainly the target mutation. The CRISPR-dCas9-based artificial transcription factors (ATFs) could be used in cancer therapy due to their possibility to manipulate DNA to modify target genes, activate tumor suppressor genes, silence oncogenes, and tumor resistance mechanisms for targeted therapy. In addition, drug repurposing combined with the use of CRISPR-dCas9-based ATFs could be an alternative cancer treatment to reduce cancer mortality. The aim of this review is to describe the potential of the repurposed drugs combined with CRISPR-dCas9-based ATFs to improve the efficacy of cancer treatment, discussing the possible advantages and disadvantages.

Overview on Anticancer Drug Design and Development

2018 ◽  
Vol 25 (15) ◽  
pp. 1704-1719 ◽  
Author(s):  
Sureyya Olgen
Keyword(s):  
Kinase Inhibitors ◽  
Molecular Design ◽  
Resistance Mechanisms ◽  
Cancer Drug ◽  
Computational Techniques ◽  
Cancer Therapies ◽  
Cancer Drugs ◽  
Design Strategies ◽  
Advantages And Disadvantages ◽  
Anti Cancer

Background: Many impediments of current anti-cancer therapies have urged scientists to discover new agents. As a result of growing spectrums of new targets and strategies and recent biological and biotechnological progresses, many anti-cancer agents such as monoclonal antibodies, small molecule tyrosine kinase inhibitors and epigenetic drugs have been reached to clinical trials. Objectives: This review helps to understand the rationale for the development of inhibitors against major targets such as cell growth, proliferation, survival, angiogenesis and recent targets such as proteasome, heat shock proteins, and epigenetics. Methods: Recent approaches of the target-based anti-cancer drug developments were highlighted to giving some examples from approved agents. Many factors, such as metabolic change, hypoxia, cancer precursors and cancer resistant cells, and their effect on drug resistance mechanisms were discussed. The impacts of advanced computational techniques to identify targets of cancer and designing more selective inhibitors were explained. Results: Contributions of recent techniques such as a network analysis, the precise modes of action and computational methodologies especially simulation of bio-molecular processes to clarify targets, mechanism actions and reasons of lack of efficacy of anti-cancer drugs have been explained. The relationship between the several mechanisms and molecular design strategies has been discussed. Conclusion: This review provides an overview of important targets and design strategies of anti-cancer drugs, advantages and disadvantages of these methods and evaluation of some currently used anticancer targets in clinical studies.

scholarly journals Mechanisms of Multidrug Resistance in Cancer Chemotherapy

2020 ◽  
Vol 21 (9) ◽  
pp. 3233 ◽  
Author(s):  
Karol Bukowski ◽  
Mateusz Kciuk ◽  
Renata Kontek
Keyword(s):  
Multidrug Resistance ◽  
Cancer Treatment ◽  
Anticancer Agents ◽  
Alkylating Agents ◽  
Gene Mutations ◽  
Resistance Mechanisms ◽  
Chemotherapeutic Agents ◽  
Future Research ◽  
Repair Capacity ◽  
Dna Repair Capacity

Cancer is one of the main causes of death worldwide. Despite the significant development of methods of cancer healing during the past decades, chemotherapy still remains the main method for cancer treatment. Depending on the mechanism of action, commonly used chemotherapeutic agents can be divided into several classes (antimetabolites, alkylating agents, mitotic spindle inhibitors, topoisomerase inhibitors, and others). Multidrug resistance (MDR) is responsible for over 90% of deaths in cancer patients receiving traditional chemotherapeutics or novel targeted drugs. The mechanisms of MDR include elevated metabolism of xenobiotics, enhanced efflux of drugs, growth factors, increased DNA repair capacity, and genetic factors (gene mutations, amplifications, and epigenetic alterations). Rapidly increasing numbers of biomedical studies are focused on designing chemotherapeutics that are able to evade or reverse MDR. The aim of this review is not only to demonstrate the latest data on the mechanisms of cellular resistance to anticancer agents currently used in clinical treatment but also to present the mechanisms of action of novel potential antitumor drugs which have been designed to overcome these resistance mechanisms. Better understanding of the mechanisms of MDR and targets of novel chemotherapy agents should provide guidance for future research concerning new effective strategies in cancer treatment.

scholarly journals New Insight into Breast Cancer Cells Involving Drug Combinations for Dopamine and Serotonin Receptors

2021 ◽  
Vol 11 (13) ◽  
pp. 6082
Author(s):  
Bárbara Costa ◽  
Rita Matos ◽  
Irina Amorim ◽  
Fátima Gärtner ◽  
Nuno Vale
Keyword(s):  
Breast Cancer ◽  
Serotonin Receptors ◽  
Drug Repurposing ◽  
Cancer Therapies ◽  
Vimentin Expression ◽  
Reference Drug ◽  
Novel Treatments ◽  
Dopamine And Serotonin Receptors ◽  
Repurposed Drugs ◽  
E Cadherin

The breast cancer therapies available are insufficient, especially since first-line treatments, such as paclitaxel, result in drug resistance and their toxicity often limits their concentration. Strategies like drug repurposing are beneficial, and novel treatments can emerge by repurposing drugs that interfere with the dopamine and serotonin receptors, and thus influence tumor growth. In this study, the MTT assay was used to test the efficacy of such repurposed drugs commonly used for neurodegenerative disorders that act on the dopamine and serotonin receptors to reduce the MCF-7 cell’s viability, either by their single use or in combination with the reference drug paclitaxel. Furthermore, the expression of vimentin and E-cadherin was assayed by immunofluorescence. The dopamine receptor-altering drugs benztropine and thioridazine resulted in the strongest reduction of cell viability when combined with paclitaxel, which may be connected to the alteration of E-cadherin rather than vimentin expression. More studies are needed to understand the mechanism of action of the combinations tested and the efficacious role of dopamine and serotonin.

scholarly journals Amino Acid Metabolism in Cancer Drug Resistance

Cells ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 140
Author(s):  
Hee-Chan Yoo ◽  
Jung-Min Han
Keyword(s):  
Drug Resistance ◽  
Amino Acid ◽  
Cancer Cells ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Epigenetic Modification ◽  
Redox Homeostasis ◽  
Resistance Mechanisms ◽  
Cancer Drug ◽  
Cancer Therapies

Despite the numerous investigations on resistance mechanisms, drug resistance in cancer therapies still limits favorable outcomes in cancer patients. The complexities of the inherent characteristics of tumors, such as tumor heterogeneity and the complicated interaction within the tumor microenvironment, still hinder efforts to overcome drug resistance in cancer cells, requiring innovative approaches. In this review, we describe recent studies offering evidence for the essential roles of amino acid metabolism in driving drug resistance in cancer cells. Amino acids support cancer cells in counteracting therapies by maintaining redox homeostasis, sustaining biosynthetic processes, regulating epigenetic modification, and providing metabolic intermediates for energy generation. In addition, amino acid metabolism impacts anticancer immune responses, creating an immunosuppressive or immunoeffective microenvironment. A comprehensive understanding of amino acid metabolism as it relates to therapeutic resistance mechanisms will improve anticancer therapeutic strategies.

scholarly journals Repurposing Old Drugs into New Epigenetic Inhibitors: Promising Candidates for Cancer Treatment?

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 410 ◽  
Author(s):  
Filipa Moreira-Silva ◽  
Vânia Camilo ◽  
Vítor Gaspar ◽  
João F. Mano ◽  
Rui Henrique ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Drug Repurposing ◽  
Inhibitory Effect ◽  
Epigenetic Alterations ◽  
Effective Strategies ◽  
Epigenetic Machinery ◽  
Traditional Drug ◽  
Repurposed Drugs ◽  
Old Drugs

Epigenetic alterations, as a cancer hallmark, are associated with cancer initiation, progression and aggressiveness. Considering, however, that these alterations are reversible, drugs that target epigenetic machinery may have an inhibitory effect upon cancer treatment. The traditional drug discovery pathway is time-consuming and expensive, and thus, new and more effective strategies are required. Drug Repurposing (DR) comprises the discovery of a new medical indication for a drug that is approved for another indication, which has been recalled, that was not accepted or failed to prove efficacy. DR presents several advantages, mainly reduced resources, absence of the initial target discovery process and the reduced time necessary for the drug to be commercially available. There are numerous old drugs that are under study as repurposed epigenetic inhibitors which have demonstrated promising results in in vitro tumor models. Herein, we summarize the DR process and explore several repurposed drugs with different epigenetic targets that constitute promising candidates for cancer treatment, highlighting their mechanisms of action.

scholarly journals Nanoparticles for Cancer Therapy: Current Progress and Challenges

2021 ◽  
Author(s):  
Shreelaxmi Gavas ◽  
Sameer Quazi ◽  
Tomasz Karpiński
Keyword(s):  
Multidrug Resistance ◽  
Cancer Treatment ◽  
Resistance Mechanisms ◽  
Multi Drug Resistance ◽  
Cancer Therapies ◽  
Therapeutic Implications ◽  
Current Perspective ◽  
Reduced Toxicity

Cancer is one of the leading causes of death and morbidity with a complex pathophysiology. Traditional cancer therapies include chemotherapy, radiation therapy, targeted therapy, and immunotherapy. However, limitations such as lack of specificity, cytotoxicity, and multi-drug resistance pose a substantial challenge for favorable cancer treatment. The advent of nanotechnology has revolutionized the arena of cancer diagnosis and treatment. Nanoparticles (1-100nm) can be used in the treatment of cancer owing to their specific advantages such as biocompatibility, reduced toxicity, more excellent stability, enhanced permeability and retention effect, and precise targeting. Nanoparticles are classified into several main categories. The nanoparticle drug delivery system is particular and utilizes tumor and tumor environment characteristics. Nanoparticles not only solve the limitations of conventional cancer treatment but also overcome multidrug resistance. Additionally, as new multidrug resistance mechanisms are unraveled and studied, nanoparticles are being investigated more vigorously. Various therapeutic implications of nano-formulations have created brand new perspectives for cancer treatment. However, a majority of the research is limited to in vivo and in vitro studies, and the number of nano-drugs that are approved has not much amplified over the years. In this review, we discuss numerous types of nanoparticles, targeting mechanisms along with approved nanotherapeutics for oncological implications in cancer treatment. Further, we also summarize the current perspective, advantages, and challenges in clinical translation.

scholarly journals Nanoparticles for Cancer Therapy: Current Progress and Challenges

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shreelaxmi Gavas ◽  
Sameer Quazi ◽  
Tomasz M. Karpiński
Keyword(s):  
Multidrug Resistance ◽  
Cancer Treatment ◽  
Resistance Mechanisms ◽  
Multi Drug Resistance ◽  
Cancer Therapies ◽  
Therapeutic Implications ◽  
Current Perspective ◽  
Reduced Toxicity

AbstractCancer is one of the leading causes of death and morbidity with a complex pathophysiology. Traditional cancer therapies include chemotherapy, radiation therapy, targeted therapy, and immunotherapy. However, limitations such as lack of specificity, cytotoxicity, and multi-drug resistance pose a substantial challenge for favorable cancer treatment. The advent of nanotechnology has revolutionized the arena of cancer diagnosis and treatment. Nanoparticles (1–100 nm) can be used to treat cancer due to their specific advantages such as biocompatibility, reduced toxicity, more excellent stability, enhanced permeability and retention effect, and precise targeting. Nanoparticles are classified into several main categories. The nanoparticle drug delivery system is particular and utilizes tumor and tumor environment characteristics. Nanoparticles not only solve the limitations of conventional cancer treatment but also overcome multidrug resistance. Additionally, as new multidrug resistance mechanisms are unraveled and studied, nanoparticles are being investigated more vigorously. Various therapeutic implications of nanoformulations have created brand new perspectives for cancer treatment. However, most of the research is limited to in vivo and in vitro studies, and the number of approved nanodrugs has not much amplified over the years. This review discusses numerous types of nanoparticles, targeting mechanisms, and approved nanotherapeutics for oncological implications in cancer treatment. Further, we also summarize the current perspective, advantages, and challenges in clinical translation.

A Review of Drug Side Effect Identification Methods

2020 ◽  
Vol 26 (26) ◽  
pp. 3096-3104 ◽  
Author(s):  
Shuai Deng ◽  
Yige Sun ◽  
Tianyi Zhao ◽  
Yang Hu ◽  
Tianyi Zang
Keyword(s):  
Side Effects ◽  
Future Research ◽  
Drug Side Effects ◽  
Important Indicator ◽  
Advantages And Disadvantages ◽  
Key Points ◽  
Network Methods ◽  
Future Research Directions ◽  
The One ◽  
Approved Drugs

Drug side effects have become an important indicator for evaluating the safety of drugs. There are two main factors in the frequent occurrence of drug safety problems; on the one hand, the clinical understanding of drug side effects is insufficient, leading to frequent adverse drug reactions, while on the other hand, due to the long-term period and complexity of clinical trials, side effects of approved drugs on the market cannot be reported in a timely manner. Therefore, many researchers have focused on developing methods to identify drug side effects. In this review, we summarize the methods of identifying drug side effects and common databases in this field. We classified methods of identifying side effects into four categories: biological experimental, machine learning, text mining and network methods. We point out the key points of each kind of method. In addition, we also explain the advantages and disadvantages of each method. Finally, we propose future research directions.

Clinical applications of circulating tumor DNA in monitoring breast cancer drug resistance

2020 ◽  
Vol 16 (34) ◽  
pp. 2863-2878
Author(s):  
Yang Liu ◽  
Qian Du ◽  
Dan Sun ◽  
Ruiying Han ◽  
Mengmeng Teng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Resistance Mechanisms ◽  
Clinical Applications ◽  
Current Status ◽  
Cancer Drug ◽  
Genomic Alteration ◽  
Tumor Dna

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide. Unfortunately, treatments often fail because of the development of drug resistance, the underlying mechanisms of which remain unclear. Circulating tumor DNA (ctDNA) is free DNA released into the blood by necrosis, apoptosis or direct secretion by tumor cells. In contrast to repeated, highly invasive tumor biopsies, ctDNA reflects all molecular alterations of tumors dynamically and captures both spatial and temporal tumor heterogeneity. Highly sensitive technologies, including personalized digital PCR and deep sequencing, make it possible to monitor response to therapies, predict drug resistance and tailor treatment regimens by identifying the genomic alteration profile of ctDNA, thereby achieving precision medicine. This review focuses on the current status of ctDNA biology, the technologies used to detect ctDNA and the potential clinical applications of identifying drug resistance mechanisms by detecting tumor-specific genomic alterations in breast cancer.

Cancer and Cancer Treatment-Related Cognitive Impairment

2019 ◽  
pp. 60-83
Author(s):  
James C.  Root ◽  
Elizabeth Ryan ◽  
Tim A. Ahles
Keyword(s):  
Cancer Survivors ◽  
Cancer Treatment ◽  
Clinical Presentation ◽  
Functional Neuroimaging ◽  
Theoretical Models ◽  
Future Research ◽  
Cognitive Changes ◽  
Central Nervous System Cancer ◽  
Pharmacologic Treatments

As the population of cancer survivors has grown into the millions, there is increasing emphasis on understanding how late effects of treatment impact survivors’ ability return to work/school, ability to function and live independently, and overall quality of life. Cognitive changes are one of the most feared problems among cancer survivors. This chapter describes the growing literature examining cognitive changes associated with non-central nervous system cancer and cancer treatment. Typical elements of cancer treatment are discussed, followed by a description of clinical presentation, self-reported and objectively assessed cognitive findings, and results of structural and functional neuroimaging research. Genetic and other risk factors for cognitive decline following treatment are identified and discussed, together with biomarkers and animal models of treatment-related effects. This is followed by a discussion of behavioral and pharmacologic treatments. Finally, challenges and recommendations for future research are provided to help guide subsequent research and theoretical models.

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