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 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.

Fanconi Anemia DNA Repair Pathway as a New Mechanism to Exploit Cancer Drug Resistance

2020 ◽  
Vol 20 (9) ◽  
pp. 779-787
Author(s):  
Kajal Ghosal ◽  
Christian Agatemor ◽  
Richard I. Han ◽  
Amy T. Ku ◽  
Sabu Thomas ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dna Repair ◽  
Fanconi Anemia ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Cancer Drugs ◽  
Repair Pathway ◽  
Cancer Drug Resistance ◽  
Anti Cancer ◽  
Cancerous Cells

Chemotherapy employs anti-cancer drugs to stop the growth of cancerous cells, but one common obstacle to the success is the development of chemoresistance, which leads to failure of the previously effective anti-cancer drugs. Resistance arises from different mechanistic pathways, and in this critical review, we focus on the Fanconi Anemia (FA) pathway in chemoresistance. This pathway has yet to be intensively researched by mainstream cancer researchers. This review aims to inspire a new thrust toward the contribution of the FA pathway to drug resistance in cancer. We believe an indepth understanding of this pathway will open new frontiers to effectively treat drug-resistant cancer.

Kinase Inhibitors Targeting Anti-angiogenesis as Anti-cancer Therapies

2012 ◽  
Vol 1 (4) ◽  
pp. 335-346 ◽  
Author(s):  
Jing Liu ◽  
Feiyang Liu ◽  
David L. Waller ◽  
Junfeng Wang ◽  
Qingsong Liu
Keyword(s):  
Kinase Inhibitors ◽  
Cancer Therapies ◽  
Anti Cancer

Prevascularized, Co-Culture Model for Breast Cancer Drug Development

2012 ◽  
Author(s):  
Lauren Marshall ◽  
Isabel Löwstedt ◽  
Paul Gatenholm ◽  
Joel Berry
Keyword(s):  
Breast Cancer ◽  
Drug Development ◽  
Three Dimensional ◽  
Human Tumor ◽  
3D Models ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Anti Cancer

The objective of this study was to create 3D engineered tissue models to accelerate identification of safe and efficacious breast cancer drug therapies. It is expected that this platform will dramatically reduce the time and costs associated with development and regulatory approval of anti-cancer therapies, currently a multi-billion dollar endeavor [1]. Existing two-dimensional (2D) in vitro and in vivo animal studies required for identification of effective cancer therapies account for much of the high costs of anti-cancer medications and health insurance premiums borne by patients, many of whom cannot afford it. An emerging paradigm in pharmaceutical drug development is the use of three-dimensional (3D) cell/biomaterial models that will accurately screen novel therapeutic compounds, repurpose existing compounds and terminate ineffective ones. In particular, identification of effective chemotherapies for breast cancer are anticipated to occur more quickly in 3D in vitro models than 2D in vitro environments and in vivo animal models, neither of which accurately mimic natural human tumor environments [2]. Moreover, these 3D models can be multi-cellular and designed with extracellular matrix (ECM) function and mechanical properties similar to that of natural in vivo cancer environments [3].

scholarly journals Role of HDAC3-miRNA-CAGE Network in Anti-Cancer Drug-Resistance

2018 ◽  
Vol 20 (1) ◽  
pp. 51 ◽  
Author(s):  
Yoojung Kwon ◽  
Youngmi Kim ◽  
Hyun Jung ◽  
Dooil Jeoung
Keyword(s):  
Molecular Networks ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Angiogenic Potential ◽  
Histone Deacetylase 3 ◽  
Cancer Drug Resistance ◽  
Tumorigenic Potential ◽  
Anti Cancer ◽  
Cancer Testis

Histone modification is associated with resistance to anti-cancer drugs. Epigenetic modifications of histones can regulate resistance to anti-cancer drugs. It has been reported that histone deacetylase 3 (HDAC3) regulates responses to anti-cancer drugs, angiogenic potential, and tumorigenic potential of cancer cells in association with cancer-associated genes (CAGE), and in particular, a cancer/testis antigen gene. In this paper, we report the roles of microRNAs that regulate the expression of HDAC3 and CAGE involved in resistance to anti-cancer drugs and associated mechanisms. In this review, roles of HDAC3-miRNAs-CAGE molecular networks in resistance to anti-cancer drugs, and the relevance of HDAC3 as a target for developing anti-cancer drugs are discussed.

scholarly journals Coherent Raman Scattering Microscopy in Oncology Pharmacokinetic Research

2021 ◽  
Vol 12 ◽  
Author(s):  
Junjie Zeng ◽  
Wenying Zhao ◽  
Shuhua Yue
Keyword(s):  
Raman Scattering ◽  
High Speed ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
High Speed Imaging ◽  
Coherent Raman Scattering ◽  
Anti Cancer ◽  
Coherent Raman

The high attrition rates of anti-cancer drugs during clinical development remains a bottleneck problem in pharmaceutical industry. This is partially due to the lack of quantitative, selective, and rapid readouts of anti-cancer drug activity in situ with high resolution. Although fluorescence microscopy has been commonly used in oncology pharmacological research, fluorescent labels are often too large in size for small drug molecules, and thus may disturb the function or metabolism of these molecules. Such challenge can be overcome by coherent Raman scattering microscopy, which is capable of chemically selective, highly sensitive, high spatial resolution, and high-speed imaging, without the need of any labeling. Coherent Raman scattering microscopy has tremendously improved the understanding of pharmaceutical materials in the solid state, pharmacokinetics of anti-cancer drugs and nanocarriers in vitro and in vivo. This review focuses on the latest applications of coherent Raman scattering microscopy as a new emerging platform to facilitate oncology pharmacokinetic research.

Ultra-low voltage triggered release of an anti-cancer drug from polypyrrole nanoparticles

Nanoscale ◽  
2018 ◽  
Vol 10 (20) ◽  
pp. 9773-9779 ◽  
Author(s):  
Devleena Samanta ◽  
Niloufar Hosseini-Nassab ◽  
Aidan D. McCarty ◽  
Richard N. Zare
Keyword(s):  
Low Voltage ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Triggered Release ◽  
Redox Active ◽  
Anti Cancer ◽  
Polypyrrole Nanoparticles

Redox-active anti-cancer drugs can be released without compromising their bioactivity from polypyrrole nanoparticles that respond to ultra-low voltages (−75 mV).

Surfactant-Based Anhydrous Nano Carrier System for Poorly Aqueous Soluble Anti-Cancer Drugs

2021 ◽  
pp. 413-432
Author(s):  
Shekhar Verma ◽  
Nagendra Chandrawanshi ◽  
Vishal Jain
Keyword(s):  
Controlled Release ◽  
Primary Objective ◽  
Water Soluble ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Carrier System ◽  
Anti Cancer ◽  
New Chemical Entities ◽  
Poorly Water Soluble ◽  
Nano Emulsion

Around 40% of new chemical entities and drugs are lipophilic or poor aqueous soluble in nature. Among them many anti-cancer drugs are also consist lipophilic properties. Available poorly water soluble anti-cancer drugs are paclitaxel, etoposide, and docetaxel. To get better stability of those anti-cancer drug via encapsulation and searching suitable carrier system for the controlled release, design and development requires of anhydrous nano carrier system. However, to deliver and entrapment of these kind of anti-cancer drugs are very essential with avoidance of water free preparation to get suitable controlled release application and achieve targeting site. The primary objective of proposed chapter is to develop and design novel stable anhydrous or non-aqueous nano emulsion carrier system and provide suitable carrier system for poorly aqueous soluble anti-cancer drugs. Another important aim is to design and develop better stabilizing agent by combining different type of surfactant, co-surfactant, and co-solvent.

scholarly journals Exploring the Diversity of the Marine Environment for New Anti-cancer Compounds

2021 ◽  
Vol 7 ◽  
Author(s):  
Divya L. Dayanidhi ◽  
Beatrice C. Thomas ◽  
Joshua S. Osterberg ◽  
Mallissa Vuong ◽  
Giselle Vargas ◽  
...  
Keyword(s):  
Terrestrial Ecosystems ◽  
Cancer Therapies ◽  
Clinical Use ◽  
Marine Environments ◽  
Cancer Drugs ◽  
Hallmarks Of Cancer ◽  
Natural Sources ◽  
Anti Cancer ◽  
Almost All ◽  
Untapped Resource

Marine ecosystems contain over 80% of the world’s biodiversity, and many of these organisms have evolved unique adaptations enabling survival in diverse and challenging environments. The biodiversity within the world’s oceans is a virtually untapped resource for the isolation and development of novel compounds, treatments, and solutions to combat human disease. In particular, while over half of our anti-cancer drugs are derived from natural sources, almost all of these are from terrestrial ecosystems. Yet, even from the limited analyses to date, a number of marine-derived anti-cancer compounds have been approved for clinical use, and several others are currently in clinical trials. Here, we review the current suite of marine-derived anti-cancer drugs, with a focus on how these compounds act upon the hallmarks of cancer. We highlight potential marine environments and species that could yield compounds with unique mechanisms. Continued exploration of marine environments, along with the characterization and screening of their inhabitants for unique bioactive chemicals, could prove fruitful in the hunt for novel anti-cancer therapies.

scholarly journals In silico identification of anti-cancer compounds and plants from traditional Chinese medicine database

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Shao-Xing Dai ◽  
Wen-Xing Li ◽  
Fei-Fei Han ◽  
Yi-Cheng Guo ◽  
Jun-Juan Zheng ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Supportive Role ◽  
Starting Point ◽  
Anti Cancer ◽  
Approved Drugs ◽  
Alternative Resource

Abstract There is a constant demand to develop new, effective, and affordable anti-cancer drugs. The traditional Chinese medicine (TCM) is a valuable and alternative resource for identifying novel anti-cancer agents. In this study, we aim to identify the anti-cancer compounds and plants from the TCM database by using cheminformatics. We first predicted 5278 anti-cancer compounds from TCM database. The top 346 compounds were highly potent active in the 60 cell lines test. Similarity analysis revealed that 75% of the 5278 compounds are highly similar to the approved anti-cancer drugs. Based on the predicted anti-cancer compounds, we identified 57 anti-cancer plants by activity enrichment. The identified plants are widely distributed in 46 genera and 28 families, which broadens the scope of the anti-cancer drug screening. Finally, we constructed a network of predicted anti-cancer plants and approved drugs based on the above results. The network highlighted the supportive role of the predicted plant in the development of anti-cancer drug and suggested different molecular anti-cancer mechanisms of the plants. Our study suggests that the predicted compounds and plants from TCM database offer an attractive starting point and a broader scope to mine for potential anti-cancer agents.

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