scholarly journals Can Any Drug Be Repurposed for Cancer Treatment? A Systematic Assessment of the Scientific Literature

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6236
Author(s):  
Nicolai Stransky ◽  
Peter Ruth ◽  
Matthias Schwab ◽  
Markus W. Löffler
Keyword(s):  
False Positive ◽  
Single Agent ◽  
Drug Repurposing ◽  
Reporting Quality ◽  
New Drugs ◽  
In Vivo Studies ◽  
Systematic Assessment ◽  
Anti Cancer ◽  
Pubmed Search

Drug repurposing is a complementary pathway for introducing new drugs against cancer. Broad systematic assessments of ongoing repurposing efforts in oncology are lacking, but may be helpful to critically appraise current and future efforts. Hence, we conducted a systematic PubMed search encompassing 100 frequently prescribed and 100 randomly selected drugs, and assessed the published preclinical anti-cancer effects. Furthermore, we evaluated all the identified original articles for methodological quality. We found reports indicating anti-cancer effects for 138/200 drugs, especially among frequently prescribed drugs (81/100). Most were reports suggesting single-agent activity of the drugs (61%). Basic information, such as the cell line used or control treatments utilized, were reported consistently, while more detailed information (e.g., excluded data) was mostly missing. The majority (56%) of in vivo studies reported randomizing animals, while only few articles stated that the experiments were conducted in a blinded fashion. In conclusion, we found promising reports of anti-cancer effects for the majority of the assessed drugs, but speculate that many of them are false-positive findings. Reward systems should be adjusted to encourage the widespread usage of high reporting quality and bias-reducing methodologies, aiming to decrease the rate of false-positive results, and thereby increasing the trust in the findings.

scholarly journals Virtual Drug Repurposing Study Against SARS-CoV-2 TMPRSS2 Target

2020 ◽  
Author(s):  
Serdar Durdagi
Keyword(s):  
Clinical Investigation ◽  
Binding Free Energy ◽  
Drug Repurposing ◽  
Md Simulations ◽  
Positive Control ◽  
New Drugs ◽  
In Vivo Studies ◽  
Approved Drugs

<p>Currently, the world suffers from a new coronavirus SARS-CoV-2 that causes COVID-19. Therefore, there is a need for the urgent development of novel drugs and vaccines for COVID-19. Since it can take years to develop new drugs against this disease, here we used a hybrid combined molecular modeling approach in virtual drug screening repurposing study to identify new compounds against this disease. One of the important SARS-CoV-2 targets namely type 2 transmembrane serine protease (TMPRSS2) was screened with NPC’s NIH small molecule library which includes approved drugs by FDA and compounds in clinical investigation. We used 6654 small molecules in molecular docking and top-50 docking scored compounds were initially used in short (10-ns) molecular dynamics (MD) simulations. Based on average MM/GBSA binding free energy results, long (100-ns) MD simulations were employed for the identified hits. Both binding energy results as well as crucial residues in ligand binding were also compared with a positive control TMPRSS2 inhibitor, Camostat mesylate. Based on these numerical calculations we proposed a compound (benzquercin) as strong TMPRSS2 inhibitor. If these results can be validated by in vitro and in vivo studies, benzquercin can be considered to be used as inhibitor of TMPRSS2 at the clinical studies.</p>

Sildenafil in combination therapy against cancer: A literature review

2020 ◽  
Vol 27 ◽  
Author(s):  
Rabah Iratni ◽  
Mohammed Akli Ayoub
Keyword(s):  
Combination Therapy ◽  
Drug Repurposing ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
Beneficial Effects ◽  
Chemotherapy Drugs ◽  
Anti Cancer ◽  
Hypertensive Drug

: The concept of drug repurposing and Sildenafil or blue pill are tightly linked over the years. Indeed, in addition to its initial clinical application as an anti-hypertensive drug in the pulmonary system, Sildenafil is also known for its beneficial effects in erectile dysfunction. Moreover, evidence have been accumulated to support its value in anti-cancer therapy either alone or in a combination with other clinically efficient chemotherapy drugs. In this review, we focused on the old and recent in vitro and in vivo studies demonstrating the cellular and molecular rationale for the application of Sildenafil in combination therapy in many various types of cancer. We emphasized on the different molecular targets as well as the different signaling pathways involved in cancer cells. The pro-apoptotic effect of Sildenafil through nitric oxide (NO)/ phosphodiesterase type 5 (PDE5)-dependent manner seems to be one of the most common mechanisms. However, the activation of autophagy as well as the modulation of the anti-tumor immunity constitute the other pathways triggered by Sildenafil. Overall, the studies converged to reveal the complexity of the anti-cancer potential of Sildenafil. Thus, through our review we aimed to present an updated and simplified picture of such repurposing of Sildenafil in the field of oncology.

Anti-cancer potential of some commonly used drugs

2021 ◽  
Vol 27 ◽  
Author(s):  
Shweta Dang ◽  
Pallavi Kumari
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Drug Repurposing ◽  
Cancer Therapeutics ◽  
In Vivo Studies ◽  
New Drug ◽  
Area Of Interest ◽  
Therapeutic Benefits ◽  
Anti Cancer

: Cancer is a global concern leading to millions of deaths every year. A declining trend in new drug discovery and development is becoming one of the major issues among the pharmaceutical, biotechnology industries, and regulatory agencies. New drug development is proven to be a very lengthy and costly process. The launch of a new drug takes 8-12 years and huge investments. The success rate in oncology therapeutics is also low due to toxicities at the pre-clinical and clinical trial levels. Many oncological drugs get rejected at a very promising stage, showing adverse reactions on healthy cells. Thus, exploring new therapeutic benefits of the existing, shelved drugs for their anti-cancerous action could result in a therapeutic approach preventing the toxicities which occur during clinical trials. Drug repurposing has the potential to overcome the challenges faced via conventional way of drug discovery and is becoming an area of interest for researchers and scientists. However, very few in vivo studies are conducted to prove the anti-cancerous activity of the drugs. Insufficient in vivo animal studies and a lack of human clinical trials are the lacunae in the field of drug repurposing. This review focuses on an aspect of drug repurposing for cancer therapeutics. Various studies that show that drugs approved for clinical indications other than cancer have shown promising anti-cancer activities. Some of the commonly used drugs like Benzodiazepines (Diazepam, Midzolam), Antidepressants (Imipramine, Clomipramine, and Citalopram), Antiepileptic (Valporic acid, Phenytoin), Antidiabetics (metformin), etc. have been reported to show potential activity against the cancerous cells.

scholarly journals Virtual Drug Repurposing Study Against SARS-CoV-2 TMPRSS2 Target

2020 ◽  
Author(s):  
Serdar Durdagi
Keyword(s):  
Clinical Investigation ◽  
Binding Free Energy ◽  
Drug Repurposing ◽  
Md Simulations ◽  
Positive Control ◽  
New Drugs ◽  
In Vivo Studies ◽  
Approved Drugs

<p>Currently, the world suffers from a new coronavirus SARS-CoV-2 that causes COVID-19. Therefore, there is a need for the urgent development of novel drugs and vaccines for COVID-19. Since it can take years to develop new drugs against this disease, here we used a hybrid combined molecular modeling approach in virtual drug screening repurposing study to identify new compounds against this disease. One of the important SARS-CoV-2 targets namely type 2 transmembrane serine protease (TMPRSS2) was screened with NPC’s NIH small molecule library which includes approved drugs by FDA and compounds in clinical investigation. We used 6654 small molecules in molecular docking and top-50 docking scored compounds were initially used in short (10-ns) molecular dynamics (MD) simulations. Based on average MM/GBSA binding free energy results, long (100-ns) MD simulations were employed for the identified hits. Both binding energy results as well as crucial residues in ligand binding were also compared with a positive control TMPRSS2 inhibitor, Camostat mesylate. Based on these numerical calculations we proposed a compound (benzquercin) as strong TMPRSS2 inhibitor. If these results can be validated by in vitro and in vivo studies, benzquercin can be considered to be used as inhibitor of TMPRSS2 at the clinical studies.</p>

scholarly journals Anticancer Compounds Derived from Marine Diatoms

Marine Drugs ◽  
2020 ◽  
Vol 18 (7) ◽  
pp. 356 ◽  
Author(s):  
Hanaa Ali Hussein ◽  
Mohd Azmuddin Abdullah
Keyword(s):  
Unsaturated Fatty Acids ◽  
High Surface ◽  
High Surface Area ◽  
Drug Carriers ◽  
Growth Cycle ◽  
In Vivo Studies ◽  
High Yield ◽  
Anti Cancer ◽  
Nano Medicine

Cancer is the main cause of death worldwide, so the discovery of new and effective therapeutic agents must be urgently addressed. Diatoms are rich in minerals and secondary metabolites such as saturated and unsaturated fatty acids, esters, acyl lipids, sterols, proteins, and flavonoids. These bioactive compounds have been reported as potent anti-cancer, anti-oxidant and anti-bacterial agents. Diatoms are unicellular photosynthetic organisms, which are important in the biogeochemical circulation of silica, nitrogen, and carbon, attributable to their short growth-cycle and high yield. The biosilica of diatoms is potentially effective as a carrier for targeted drug delivery in cancer therapy due to its high surface area, nano-porosity, bio-compatibility, and bio-degradability. In vivo studies have shown no significant symptoms of tissue damage in animal models, suggesting the suitability of a diatoms-based system as a safe nanocarrier in nano-medicine applications. This review presents an overview of diatoms’ microalgae possessing anti-cancer activities and the potential role of the diatoms and biosilica in the delivery of anticancer drugs. Diatoms-based antibodies and vitamin B12 as drug carriers are also elaborated.

scholarly journals The Occurrence and Biological Activity of Tormentic Acid—A Review

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3797
Author(s):  
Marta Olech ◽  
Wojciech Ziemichód ◽  
Natalia Nowacka-Jechalke
Keyword(s):  
Biological Activity ◽  
Plant Species ◽  
Current Knowledge ◽  
In Vivo Studies ◽  
Natural Sources ◽  
Anti Cancer ◽  
Biochemical Mechanisms ◽  
Tormentic Acid

This review focuses on the natural sources and pharmacological activity of tormentic acid (TA; 2α,3β,19α-trihydroxyurs-2-en-28-oic acid). The current knowledge of its occurrence in various plant species and families is summarized. Biological activity (e.g., anti-inflammatory, antidiabetic, antihyperlipidemic, hepatoprotective, cardioprotective, neuroprotective, anti-cancer, anti-osteoarthritic, antinociceptive, antioxidative, anti-melanogenic, cytotoxic, antimicrobial, and antiparasitic) confirmed in in vitro and in vivo studies is compiled and described. Biochemical mechanisms affected by TA are indicated. Moreover, issues related to the biotechnological methods of production, effective eluents, and TA derivatives are presented.

Viscum album (L) extracts in cancer treatment: a systematic review of in vitro and in vivo studies

2021 ◽  
Vol 14 (2) ◽  
pp. 52-52
Author(s):  
Aloisio Cunha de Carvalho ◽  
Leoni Villano Bonamin
Keyword(s):  
Systematic Review ◽  
Experimental Studies ◽  
Pharmaceutical Preparations ◽  
Viscum Album ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Pubmed Database ◽  
Anti Cancer

Background: Several reviews about phytotherapy and homeopathy have been published in the last years, including Viscum album (VA.L). VA is a parasite plant whose extract has anti-cancer proprieties and is used alone or in combination with conventional chemotherapy. Methods: We performed a systematic review about the in vivo and in vitro models described in the literature, including veterinary clinical trials. The literature was consulted from Pubmed database. Results: There are several kinds of pharmaceutical preparations about VA and their active principles used in experimental studies, lectin being frequently studied (alone or as an extract compound). More than 50% of available literature about VA is related to the lectin effects. On the other hand, the effects of viscotoxins are less studied. Among the in vivo experimental studies about VA and its compounds, the B16 murine melanoma is the most used model, followed by Ehrlich, Walker and Dalton tumors. The results point to the apoptotic effects, metastasis control and tumor regression. Some veterinary clinical studies about the use of VA in the treatment of sarcoid, fibrosarcoma and neuroblastoma are quoted in literature too, with interesting results. Considering the in vitro models, our review revealed that NALM6 leukemia cells, B16 melanoma and NC1-H460 lung carcinoma were the most studied tumor models, apoptosis signals being the most important findings. Only one study verified immunoglobulin and interleukin production. All consulted papers were related to phytotherapy preparations only. Conclusions: Although the literature about the anti-cancer activity of VA extract and its lectins is enough, there is a marked lack of information about viscotoxin activities and about the effects of homeopathic preparations of this plant on animal tumors and on in vitro cultivated tumor cells.

Advancements in Cancer Therapeutics

2021 ◽  
pp. 89-115
Author(s):  
Serda Kecel Gunduz ◽  
Bilge Bicak ◽  
Aysen E. Ozel
Keyword(s):  
Protein Design ◽  
Complex Structure ◽  
Cancer Therapeutics ◽  
New Drugs ◽  
In Vivo Studies ◽  
Drug Induced ◽  
Dimensional Simulation ◽  
Dynamics And Function

In this chapter, computational approaches for the discovery of new drugs that are useful for diagnosis and treatment of disease will be described in three parts. MD technique uniquely supports protein design attempts by giving information about protein dynamics associated with atomic-level descriptions of the relationship between dynamics and function. The purpose of molecular docking is to provide an estimate of the ligand-receptor complex structure using computational methods. By this estimation, the mechanism of drug binding and action are described by determining the three-dimensional simulation of drug and drug-induced macrostructure. ADME characteristics are physicochemically significant descriptors and pharmacokinetically relevant properties used to design more effective drugs and new analogs. As a result, in-silico calculations can provide robust preliminary information as to drug activity and mechanism in the drug production process, as well as in vitro and in vivo studies.

scholarly journals Nano-encapsulated tryptanthrin derivative for combined anticancer therapy via inhibiting indoleamine 2,3-dioxygenase and inducing immunogenic cell death

Nanomedicine ◽  
2019 ◽  
Vol 14 (18) ◽  
pp. 2423-2440 ◽  
Author(s):  
Canyu Yang ◽  
Bing He ◽  
Qiang Zheng ◽  
Dakuan Wang ◽  
Mengmeng Qin ◽  
...  
Keyword(s):  
Cell Death ◽  
Single Agent ◽  
Tumor Burden ◽  
Antitumor Efficacy ◽  
In Vivo Studies ◽  
Immunogenic Cell Death ◽  
Indoleamine 2,3 Dioxygenase ◽  
Tumor Tissues

Aim: We developed a polycaprolactone-based nanoparticle (NP) to encapsulate tryptanthrin derivative CY-1-4 and evaluated its antitumor efficacy. Materials & methods: CY-1-4 NPs were prepared and evaluated for their cytotoxicity and associated mechanisms, indoleamine 2,3-dioxygenase (IDO)-inhibitory ability, immunogenic cell death (ICD)-inducing ability and antitumor efficacy. Results: CY-1-4 NPs were 123 nm in size. In vitro experiments indicated that they could both induce ICD and inhibit IDO. In vivo studies indicated that a medium dose reduced 58% of the tumor burden in a B16-F10-bearing mouse model, decreased IDO expression in tumor tissues and regulated lymphocytes subsets in spleen and tumors. Conclusion: CY-1-4 is a potential antitumor candidate that could act as a single agent with combined functions of IDO inhibition and ICD induction.

scholarly journals Based on Principles and Insights of COVID-19 Epidemiology, Genome Sequencing, and Pathogenesis: Retrospective Analysis of Sinigrin and ProlixinRX (Fluphenazine) Provides Off-Label Drug Candidates

2020 ◽  
Vol 25 (10) ◽  
pp. 1123-1140
Author(s):  
Jilan Nazeam ◽  
Esraa Z. Mohammed ◽  
Mariam Raafat ◽  
Mariam Houssein ◽  
Asmaa Elkafoury ◽  
...  
Keyword(s):  
Natural Products ◽  
Evidence Synthesis ◽  
Drug Repurposing ◽  
New Drugs ◽  
Future Research ◽  
Nitrogenous Compounds ◽  
Future Research Agenda ◽  
Starting Point

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen of pandemic coronavirus disease 2019 (COVID-19). So far, no approved therapy has been developed to halt the spread of the pathogen, and unfortunately, the strategies for developing a new therapy will require a long time and very extensive resources. Therefore, drug repurposing has emerged as an ideal strategy toward a smart, versatile, quick way to confine the lethal disease. In this endeavor, natural products have been an untapped source for new drugs. This review represents the confederated experience of multidisciplinary researchers of 99 articles using several databases: Google Scholar, Science Direct, MEDLINE, Web of Science, Scopus, and PubMed. To establish the hypothesis, a Bayesian perspective of a systematic review was used to outline evidence synthesis. Our docking documentation of 69 compounds and future research agenda assumptions were directed toward finding an effective and economic anti-COVID-19 treatment from natural products. Glucosinolate, flavones, and sulfated nitrogenous compounds demonstrate direct anti-SARS-CoV-2 activity through inhibition protease enzymes and may be considered potential candidates against coronavirus. These findings could be a starting point to initiate an integrative study that may encompass interested scientists and research institutes to test the hypothesis in vitro, in vivo, and in clinics after satisfying all ethical requirements.

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