scholarly journals Chemoresistance of Cancer Cells: Requirements of Tumor Microenvironment-mimicking In Vitro Models in Anti-Cancer Drug Development

Theranostics ◽  
2018 ◽  
Vol 8 (19) ◽  
pp. 5259-5275 ◽  
Author(s):  
Yeonho Jo ◽  
Nakwon Choi ◽  
Kyobum Kim ◽  
Hyung-Jun Koo ◽  
Jonghoon Choi ◽  
...  
Author(s):  
Lauren Marshall ◽  
Isabel Löwstedt ◽  
Paul Gatenholm ◽  
Joel Berry

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].


Lab on a Chip ◽  
2019 ◽  
Vol 19 (3) ◽  
pp. 369-386 ◽  
Author(s):  
Menglin Shang ◽  
Ren Hao Soon ◽  
Chwee Teck Lim ◽  
Bee Luan Khoo ◽  
Jongyoon Han

Microfluidic tumor model has the unique advantage of recapitulating tumor microenvironment in a comparatively easier and representative fashion. In this review, we aim to focus more on the possibility of generating clinically actionable information from these microfluidic systems, not just scientific insight.


Author(s):  
Patrick J. Bednarski ◽  
Katharina Korpis ◽  
Aron F. Westendorf ◽  
Steffi Perfahl ◽  
Renate Grünert

Various Pt IV diazides have been investigated over the years as light-activatable prodrugs that interfere with cell proliferation, accumulate in cancer cells and cause cell death. The potencies of the complexes vary depending on the substituted amines (pyridine=piperidine>ammine) as well as the coordination geometry ( trans diazide> cis ). Light-activated Pt IV diazides tend to be less specific than cisplatin at inhibiting cancer cell growth, but cells resistant to cisplatin show little cross-resistance to Pt IV diazides. Platinum is accumulated in the cancer cells to a similar level as cisplatin, but only when activated by light, indicating that reactive Pt species form photolytically. Studies show that Pt also becomes attached to cellular DNA upon the light activation of various Pt IV diazides. Structures of some of the photolysis products were elucidated by LC–MS/MS; monoaqua- and diaqua-Pt II complexes form that are reactive towards biomolecules such as calf thymus DNA. Platination of calf thymus DNA can be blocked by the addition of nucleophiles such as glutathione and chloride, further evidence that aqua-Pt II species form upon irradiation. Evidence is presented that reactive oxygen species may be generated in the first hours following photoactivation. Cell death does not take the usual apoptotic pathways seen with cisplatin, but appears to involve autophagy. Thus, photoactivated diazido-Pt IV complexes represent an interesting class of potential anti-cancer agents that can be selectively activated by light and kill cells by a mechanism different to the anti-cancer drug cisplatin.


Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2903 ◽  
Author(s):  
Yong Zhang ◽  
Jingjing Xu ◽  
Yuezhou Yu ◽  
Wenhao Shang ◽  
Anpei Ye

A novel anti-cancer drug sensitivity testing (DST) approach was developed based on in vitro single-cell Raman spectrum intensity (RSI). Generally, the intensity of Raman spectra (RS) for a single living cell treated with drugs positively relates to the sensitivity of the cells to the drugs. In this study, five cancer cell lines (BGC 823, SGC 7901, MGC 803, AGS, and NCI-N87) were exposed to three cytotoxic compounds or to combinations of these compounds, and then they were evaluated for their responses with RSI. The results of RSI were consistent with conventional DST methods. The parametric correlation coefficient for the RSI and Methylthiazolyl tetrazolium assay (MTT) was 0.8558 ± 0.0850, and the coefficient of determination was calculated as R2 = 0.9529 ± 0.0355 for fitting the dose–response curve. Moreover, RSI data for NCI-N87 cells treated by trastuzumab, everolimus (cytostatic), and these drugs in combination demonstrated that the RSI method was suitable for testing the sensitivity of cytostatic drugs. Furthermore, a heterogeneity coefficient H was introduced for quantitative characterization of the heterogeneity of cancer cells treated by drugs. The largest possible variance between RSs of cancer cells were quantitatively obtained using eigenvalues of principal component analysis (PCA). The ratio of H between resistant cells and sensitive cells was greater than 1.5, which suggested the H-value was effective to describe the heterogeneity of cancer cells. Briefly, the RSI method might be a powerful tool for simple and rapid detection of the sensitivity of tumor cells to anti-cancer drugs and the heterogeneity of their responses to these drugs.


2017 ◽  
Vol 5 (3) ◽  
pp. 532-550 ◽  
Author(s):  
Muhammad Gulfam ◽  
Teresa Matini ◽  
Patrícia F. Monteiro ◽  
Raphaël Riva ◽  
Hilary Collins ◽  
...  

PEG-poly(caprolactone) co-polymers with disulfide-linked cores are highly efficient for delivery of the anti-cancer drug methotrexate in vitro.


2021 ◽  
Vol 22 (5) ◽  
pp. 2408
Author(s):  
Bin Zhang ◽  
Jiamei Zou ◽  
Qiting Zhang ◽  
Ze Wang ◽  
Ning Wang ◽  
...  

Eukaryotic elongation factor 2 kinase (eEF2K or Ca2+/calmodulin-dependent protein kinase, CAMKIII) is a new member of an atypical α-kinase family different from conventional protein kinases that is now considered as a potential target for the treatment of cancer. This protein regulates the phosphorylation of eukaryotic elongation factor 2 (eEF2) to restrain activity and inhibit the elongation stage of protein synthesis. Mounting evidence shows that eEF2K regulates the cell cycle, autophagy, apoptosis, angiogenesis, invasion, and metastasis in several types of cancers. The expression of eEF2K promotes survival of cancer cells, and the level of this protein is increased in many cancer cells to adapt them to the microenvironment conditions including hypoxia, nutrient depletion, and acidosis. The physiological function of eEF2K and its role in the development and progression of cancer are here reviewed in detail. In addition, a summary of progress for in vitro eEF2K inhibitors from anti-cancer drug discovery research in recent years, along with their structure–activity relationships (SARs) and synthetic routes or natural sources, is also described. Special attention is given to those inhibitors that have been already validated in vivo, with the overall aim to provide reference context for the further development of new first-in-class anti-cancer drugs that target eEF2K.


2015 ◽  
Vol 7 (24) ◽  
pp. 10162-10169 ◽  
Author(s):  
Qifei Li ◽  
Lifu Xiao ◽  
Sitaram Harihar ◽  
Danny R. Welch ◽  
Elizabeth Vargis ◽  
...  

Breast cancer cells with or without BRMS1 in response to doxorubicin (DOX).


2021 ◽  
Vol 11 ◽  
Author(s):  
Andrew M. K. Law ◽  
Laura Rodriguez de la Fuente ◽  
Thomas J. Grundy ◽  
Guocheng Fang ◽  
Fatima Valdes-Mora ◽  
...  

Over 90% of potential anti-cancer drug candidates results in translational failures in clinical trials. The main reason for this failure can be attributed to the non-accurate pre-clinical models that are being currently used for drug development and in personalised therapies. To ensure that the assessment of drug efficacy and their mechanism of action have clinical translatability, the complexity of the tumor microenvironment needs to be properly modelled. 3D culture models are emerging as a powerful research tool that recapitulates in vivo characteristics. Technological advancements in this field show promising application in improving drug discovery, pre-clinical validation, and precision medicine. In this review, we discuss the significance of the tumor microenvironment and its impact on therapy success, the current developments of 3D culture, and the opportunities that advancements that in vitro technologies can provide to improve cancer therapeutics.


Author(s):  
Neha V. Bhilare ◽  
Pratibha B. Auti ◽  
Vinayak S. Marulkar ◽  
Vilas J. Pise

: Thiophenes are one among the abundantly found heterocyclic ring systems in many biologically active compounds. Moreover various substituted thiophenes exert numerous pharmacological actions on account of their isosteric resemblance with compounds of natural origin thus rendering them with diverse actions like antibacterial, antifungal, antiviral, anti-inflammatory, analgesic, antiallergic, hypotensives etc.. In this review we specifically explore the chemotherapeutic potential of variety of structures consisting of thiophene scaffolds as prospective anticancer agents.


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