The Evaluation of Animal Models in the Development of Anticancer Agents: From Preclinical to Clinical Tests

2019 ◽  
Vol 19 (4) ◽  
pp. 277-284
Author(s):  
Jie Wang ◽  
Haiyan Dong ◽  
Jian Liu ◽  
Ning Zheng ◽  
Xiaodong Xie ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Drug Effects ◽  
Relevant Information ◽  
Clinical Tests ◽  
Toxicological Studies ◽  
Anti Cancer ◽  
Online Sources

Background: One of the main reasons for most of the anticancer drugs to fail in the late preclinical testing and early clinical trials is the differences in drug effects observed from animals and patients, and the challenge has been to find a balance to reduce the inherent differences from species. Objective: Predicting safe starting doses and dosing schedules for human clinical trials is the main purpose of toxicological studies of anticancer drugs. Methods: Relevant information and data were assimilated from manuscripts, congress publications, and online sources. Results: We systematically overview the cons and pros of animal models and briefed the ways to determine human clinical starting doses derived from animal toxicological studies for anticancer drugs. Conclusion: This information helps smart select the suitable predictive model for anti-cancer drugs with the different mechanisms and emphasized the pharmaceutical challenges behind and ahead.

scholarly journals Anticancer Agents from Diverse Natural Sources

2014 ◽  
Vol 9 (11) ◽  
pp. 1934578X1400901 ◽  
Author(s):  
Jabeena Khazir ◽  
Darren L. Riley ◽  
Lynne A. Pilcher ◽  
Pieter De-Maayer ◽  
Bilal Ahmad Mir
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Anticancer Agents ◽  
Marine Organisms ◽  
New Drugs ◽  
Human Diseases ◽  
Cancer Drugs ◽  
Natural Sources ◽  
Anti Cancer ◽  
Ancient Times

This review attempts to portray the discovery and development of anticancer agents/drugs from diverse natural sources. Natural molecules from these natural sources including plants, microbes and marine organisms have been the basis of treatment of human diseases since the ancient times. Compounds derived from nature have been important sources of new drugs and also serve as templates for synthetic modification. Many successful anti-cancer drugs currently in use are naturally derived or their analogues and many more are under clinical trials. This review aims to highlight the invaluable role that natural products have played, and continue to play, in the discovery of anticancer agents.

Recent Progress in Histone Deacetylase Inhibitors as Anticancer Agents

2020 ◽  
Vol 27 (15) ◽  
pp. 2449-2493 ◽  
Author(s):  
Loredana Cappellacci ◽  
Diego R. Perinelli ◽  
Filippo Maggi ◽  
Mario Grifantini ◽  
Riccardo Petrelli
Keyword(s):  
Clinical Trials ◽  
Histone Deacetylase ◽  
Anticancer Agents ◽  
Histone Deacetylase Inhibitors ◽  
Cyclic Peptide ◽  
Hdac Inhibitors ◽  
Cancer Therapeutics ◽  
Rational Drug Design ◽  
Modeling Tools ◽  
Anti Cancer

Histone Deacetylase (HDAC) inhibitors are a relatively new class of anti-cancer agents that play important roles in epigenetic or non-epigenetic regulation, inducing death, apoptosis, and cell cycle arrest in cancer cells. Recently, their use has been clinically validated in cancer patients resulting in the approval by the FDA of four HDAC inhibitors, vorinostat, romidepsin, belinostat and panobinostat, used for the treatment of cutaneous/peripheral T-cell lymphoma and multiple myeloma. Many more HDAC inhibitors are at different stages of clinical development for the treatment of hematological malignancies as well as solid tumors. Also, clinical trials of several HDAC inhibitors for use as anti-cancer drugs (alone or in combination with other anti-cancer therapeutics) are ongoing. In the intensifying efforts to discover new, hopefully, more therapeutically efficacious HDAC inhibitors, molecular modelingbased rational drug design has played an important role. In this review, we summarize four major structural classes of HDAC inhibitors (hydroxamic acid derivatives, aminobenzamide, cyclic peptide and short-chain fatty acids) that are in clinical trials and different computer modeling tools available for their structural modifications as a guide to discover additional HDAC inhibitors with greater therapeutic utility.

Recent Progress in the Development of Quinoline Derivatives for the Exploitation of Anti-cancer Agents

2020 ◽  
Vol 20 ◽  
Author(s):  
Ruo-Jun Man ◽  
Nasreen Jeelani ◽  
Chongchen Zhou ◽  
Yu-Shun Yang
Keyword(s):  
Clinical Trials ◽  
Anticancer Agents ◽  
Rational Design ◽  
Biological Macromolecules ◽  
Quinoline Derivatives ◽  
Specific Topic ◽  
Anti Cancer ◽  
The World ◽  
New Challenges ◽  
The Relationship

Background: Along with the progress in medicine and therapies, the exploitation of anti-cancer agents focused more on the vital signaling pathways and key biological macromolecules. With rational design and advanced synthesis, quinoline derivatives have been utilized frequently in medicinal chemistry, especially in developing anti-cancer drugs or candidates. Methods: Using DOI searching, articles published before 2020 all over the world have been reviewed as comprehensively as possible. Results: In this review, we selected the representative quinoline derivate drugs in market or clinical trials, classified them into five major categories with detailed targets according to their main mechanisms, discussed the relationship within the same mechanism, and generated a summative discussion with prospective expectations. For each mechanism, the introduction of the target was presented, with the typical examples of quinoline derivate drugs. Conclusion: This review has highlighted the quinoline drugs or candidates, suited them into corresponding targets in their pathways, summarized and discussed. We hope that this review may help the researchers who are interested in discovering quinoline derivate anticancer agents obtain considerable understanding in this specific topic. Through the flourishing period and the vigorous strategies in clinical trials, quinoline drugs would be potential but facing new challenges in future.

Reporting of Serious Adverse Drug Reactions of Targeted Anticancer Agents in Pivotal Phase III Clinical Trials

2011 ◽  
Vol 29 (2) ◽  
pp. 174-185 ◽  
Author(s):  
Bostjan Seruga ◽  
Lynn Sterling ◽  
Lisa Wang ◽  
Ian F. Tannock
Keyword(s):  
Clinical Trials ◽  
Anticancer Drugs ◽  
Adverse Drug Reactions ◽  
Anticancer Agents ◽  
Randomized Clinical Trials ◽  
Phase Iii ◽  
Limited Information ◽  
Drug Reactions ◽  
Pivotal Phase ◽  
Initial Drug

Purpose Oncologists prescribe anticancer drugs based on results of phase III randomized clinical trials (RCTs), but some safety concerns appear only later in updated drug labels. Here, we analyze adverse drug reactions (ADRs) of targeted anticancer agents from updated drug labels and their reporting in corresponding pivotal RCTs. Methods We searched the US Food and Drug Administration (FDA) Web site for approved targeted anticancer drugs with updates of their labels related to safety in 2008 and 2009 and at least one RCT referenced in the updated drug label. For each drug, serious ADRs, including potentially fatal ADRs, were identified from the updated label. Published reports of RCTs referenced in the label were searched to determine whether they described these ADRs. Results We identified 12 eligible targeted anticancer agents with 36 corresponding RCTs referenced in updated drug labels. There were 76 serious ADRs reported in updated drug labels, and 50% (n = 38) were potentially fatal. Of these, 39% (n = 30) of all serious ADRs and 39% (n = 15) of potentially fatal ADRs were not described in any published report of RCTs, whereas 49% and 58%, respectively, were not described in initial drug labels. After a median 4.3 years between initial approval and update of drug labels, 42% (n = 5) of targeted cancer agents acquired one or more boxed warnings (the highest level of FDA alert). Conclusion Published reports of pivotal RCTs and initial drug labels contain limited information about serious ADRs of targeted anticancer agents. Rare but serious ADRs may be important causes of morbidity and mortality in general oncologic practice.

scholarly journals Alkaloids Isolated from Natural Herbs as the Anticancer Agents

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Jin-Jian Lu ◽  
Jiao-Lin Bao ◽  
Xiu-Ping Chen ◽  
Min Huang ◽  
Yi-Tao Wang
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Chemical Compounds ◽  
Mechanisms Of Action ◽  
Anticancer Properties ◽  
Important Chemical

Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation and antimetastasis effects on various types of cancers bothin vitroandin vivo. Alkaloids, such as camptothecin and vinblastine, have already been successfully developed into anticancer drugs. This paper focuses on the naturally derived alkaloids with prospective anticancer properties, such as berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine, and summarizes the mechanisms of action of these compounds. Based on the information in the literature that is summarized in this paper, the use of alkaloids as anticancer agents is very promising, but more research and clinical trials are necessary before final recommendations on specific alkaloids can be made.

scholarly journals Marine-Derived Anticancer Agents: Clinical Benefits, Innovative Mechanisms, and New Targets

Marine Drugs ◽  
2019 ◽  
Vol 17 (6) ◽  
pp. 329 ◽  
Author(s):  
Renato B. Pereira ◽  
Nikolai M. Evdokimov ◽  
Florence Lefranc ◽  
Patrícia Valentão ◽  
Alexander Kornienko ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Molecular Targets ◽  
Mechanisms Of Action ◽  
Late Development ◽  
Clinical Benefits ◽  
Approved Drugs ◽  
Current Paradigm

The role of the marine environment in the development of anticancer drugs has been widely reviewed, particularly in recent years. However, the innovation in terms of clinical benefits has not been duly emphasized, although there are important breakthroughs associated with the use of marine-derived anticancer agents that have altered the current paradigm in chemotherapy. In addition, the discovery and development of marine drugs has been extremely rewarding with significant scientific gains, such as the discovery of new anticancer mechanisms of action as well as novel molecular targets. Approximately 50 years since the approval of cytarabine, the marine-derived anticancer pharmaceutical pipeline includes four approved drugs and eighteen agents in clinical trials, six of which are in late development. Thus, the dynamic pharmaceutical pipeline consisting of approved and developmental marine-derived anticancer agents offers new hopes and new tools in the treatment of patients afflicted with previously intractable types of cancer.

scholarly journals Glycosaminoglycans and Glycosaminoglycan Mimetics in Cancer and Inflammation

2019 ◽  
Vol 20 (8) ◽  
pp. 1963 ◽  
Author(s):  
Shravan Morla
Keyword(s):  
Extracellular Matrix ◽  
Clinical Trials ◽  
Animal Models ◽  
Mammalian Cells ◽  
Viral Infections ◽  
Anti Cancer ◽  
Significant Interest ◽  
Multiple Ligands ◽  
Cancer And Inflammation ◽  
Intracellular Milieu

Glycosaminoglycans (GAGs) are a class of biomolecules expressed virtually on all mammalian cells and usually covalently attached to proteins, forming proteoglycans. They are present not only on the cell surface, but also in the intracellular milieu and extracellular matrix. GAGs interact with multiple ligands, both soluble and insoluble, and modulate an important role in various physiological and pathological processes including cancer, bacterial and viral infections, inflammation, Alzheimer’s disease, and many more. Considering their involvement in multiple diseases, their use in the development of drugs has been of significant interest in both academia and industry. Many GAG-based drugs are being developed with encouraging results in animal models and clinical trials, showcasing their potential for development as therapeutics. In this review, the role GAGs play in both the development and inhibition of cancer and inflammation is presented. Further, advancements in the development of GAGs and their mimetics as anti-cancer and anti-inflammatory agents are discussed.

scholarly journals Les Effets Indésirables Digestifs De La Chimiothérapie : Cas Des Patients De L’institut National D’oncologie De Rabat (Maroc)

2016 ◽  
Vol 12 (33) ◽  
pp. 454
Author(s):  
Mustapha Ahtit ◽  
Soulaymani Abdelmajid ◽  
Khadmaoui Abderrazak ◽  
R. Benkirane ◽  
Soulaymani Bencheikh Rachida ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
Drug Effects ◽  
Adverse Drug Effects ◽  
Cancer Disease ◽  
Anticancer Chemotherapy ◽  
Anti Cancer ◽  
The Family ◽  
Anticancer Treatment ◽  
A Prospective Study

An adverse reaction of an anticancer drug is a harmful and an unintended reaction by patient suffering from cancer disease who is often polymedicated. The treatment of cancers by anti-cancer molecules produces serious adverse drug effects. The main purpose of this paper is to present and evaluate the digestive adverse effects involved in anti-cancer drugs and their potential of correlation to anticipate, prevent and improve the quality of care of patient suffering from cancer disease. This is a prospective study that that enrolled 147 patients seen between January 25 and June 25, 2009 with adverse drug reactions due to an anticancer treatment. Breast and cavum cancers present 34% of cases. The average age was 46.52 years. The sex ratio (M / F) was 0.33. During the study period 283 Adverse drug effects of anticancer drugs were collected with a predominance (132) adverse digestive effects and 32 anticancer drugs were counted on all medical prescriptions. Nausea and vomiting are the most common side effects, sometimes very severe. The availability of anti-emetics in the family of 5-HT3 serotoninergic antagonists has considerably improved the experience of patients undergoing anticancer chemotherapy, hence the importance of pharmacovigilance as a tool is to improve the quality of anticancer care.

scholarly journals Ionophores: Potential Use as Anticancer Drugs and Chemosensitizers

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 360 ◽  
Author(s):  
Vivek Kaushik ◽  
Juan Yakisich ◽  
Anil Kumar ◽  
Neelam Azad ◽  
Anand Iyer
Keyword(s):  
Clinical Trials ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Targeted Drug Delivery ◽  
Ion Homeostasis ◽  
Anticancer Activities ◽  
In Vivo Models ◽  
Potential Use

Ion homeostasis is extremely important for the survival of both normal as well as neoplastic cells. The altered ion homeostasis found in cancer cells prompted the investigation of several ionophores as potential anticancer agents. Few ionophores, such as Salinomycin, Nigericin and Obatoclax, have demonstrated potent anticancer activities against cancer stem-like cells that are considered highly resistant to chemotherapy and responsible for tumor relapse. The preclinical success of these compounds in in vitro and in vivo models have not been translated into clinical trials. At present, phase I/II clinical trials demonstrated limited benefit of Obatoclax alone or in combination with other anticancer drugs. However, future development in targeted drug delivery may be useful to improve the efficacy of these compounds. Alternatively, these compounds may be used as leading molecules for the development of less toxic derivatives.

The Animal Models for Hemorrhage and Thrombosis in the Neonate

1987 ◽  
Vol 57 (01) ◽  
pp. 118-122 ◽  
Author(s):  
C Thomas Kisker
Keyword(s):  
Animal Models ◽  
Normal Development ◽  
Relevant Information ◽  
Relevant Model ◽  
Current Information ◽  
Single Animal ◽  
Hemostatic Disorders ◽  
Thrombotic Diseases

SummaryAnimal models have added significantly to our understanding of adult hemorrhagic and thrombotic diseases. Few models, however, have been developed for studies of the hemostatic disorders in the fetus and newborn. This report reviews the current information on animal models of fetal and neonatal hemostasis. The requirements of a relevant model are addressed and previous studies using fetal and neonatal animal models are reviewed. A recommendation of a single animal for all studies of fetal and neonatal hemostasis is not possible. However, the lamb has been the most frequently studied and appears to provide relevant information regarding normal development and the factors which may adversely influence hemostasis in the fetus and newborn.

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