3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs: NUNES et al.

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Three-dimensional cell culture models, such as spheroids, can be used in the process of the development of new anticancer agents because they are able to closely mimic the main features of human solid tumors, namely their structural organization, cellular layered assembling, hypoxia, and nutrient gradients. These properties imprint to the spheroids an anticancer therapeutics resistance profile, which is similar to that displayed by human solid tumors. In this review, an overview of the drug resistance mechanisms observed in 3D tumor spheroids is provided. Furthermore, comparisons between the therapeutics resistance profile exhibited by spheroids, and 2D cell cultures are presented. Finally, examples of the therapeutic approaches that have been developed to surpass the drug resistance mechanisms exhibited by spheroids are described.

Related collections

Most cited references 124

Record: found
Abstract: found
Article: not found

Drug resistance and the solid tumor microenvironment.

Olivier Trédan, Carlos M. Galmarini, Krupa Patel … (2007)

Resistance of human tumors to anticancer drugs is most often ascribed to gene mutations, gene amplification, or epigenetic changes that influence the uptake, metabolism, or export of drugs from single cells. Another important yet little-appreciated cause of anticancer drug resistance is the limited ability of drugs to penetrate tumor tissue and to reach all of the tumor cells in a potentially lethal concentration. To reach all viable cells in the tumor, anticancer drugs must be delivered efficiently through the tumor vasculature, cross the vessel wall, and traverse the tumor tissue. In addition, heterogeneity within the tumor microenvironment leads to marked gradients in the rate of cell proliferation and to regions of hypoxia and acidity, all of which can influence the sensitivity of the tumor cells to drug treatment. In this review, we describe how the tumor microenvironment may be involved in the resistance of solid tumors to chemotherapy and discuss potential strategies to improve the effectiveness of drug treatment by modifying factors relating to the tumor microenvironment.

0 comments Cited 693 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

Targeting lactate metabolism for cancer therapeutics.

Joanne R. Doherty, John L. Cleveland (2013)

Lactate, once considered a waste product of glycolysis, has emerged as a critical regulator of cancer development, maintenance, and metastasis. Indeed, tumor lactate levels correlate with increased metastasis, tumor recurrence, and poor outcome. Lactate mediates cancer cell intrinsic effects on metabolism and has additional non-tumor cell autonomous effects that drive tumorigenesis. Tumor cells can metabolize lactate as an energy source and shuttle lactate to neighboring cancer cells, adjacent stroma, and vascular endothelial cells, which induces metabolic reprogramming. Lactate also plays roles in promoting tumor inflammation and in functioning as a signaling molecule that stimulates tumor angiogenesis. Here we review the mechanisms of lactate production and transport and highlight emerging evidence indicating that targeting lactate metabolism is a promising approach for cancer therapeutics.

0 comments Cited 481 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: found

Lactate: a metabolic key player in cancer.

Franziska Hirschhaeuser, Ulrike G A Sattler, Wolfgang Mueller-Klieser (2011)

Increased glucose uptake and accumulation of lactate, even under normoxic conditions (i.e., aerobic glycolysis or the Warburg Effect), is a common feature of cancer cells. This phenomenon clearly indicates that lactate is not a surrogate of tumor hypoxia. Tumor lactate can predict for metastases and overall survival of patients, as shown by several studies of different entities. Metastasis of tumors is promoted by lactate-induced secretion of hyaluronan by tumor-associated fibroblasts that create a milieu favorable for migration. Lactate itself has been found to induce the migration of cells and cell clusters. Furthermore, radioresistance has been positively correlated with lactate concentrations, suggesting an antioxidative capacity of lactate. Findings on interactions of tumor metabolites with immune cells indicate a contribution of lactate to the immune escape. Furthermore, lactate bridges the gap between high lactate levels in wound healing, chronic inflammation, and cancer development. Tumor cells ensure sufficient oxygen and nutrient supply for proliferation through lactate-induced secretion of VEGF, resulting in the formation of new vessels. In summary, accumulation of lactate in solid tumors is a pivotal and early event in the development of malignancies. The determination of lactate should enter further clinical trials to confirm its relevance in cancer biology. ©2011 AACR

0 comments Cited 464 times – based on 0 reviews      Review now

All references

Author and article information

Journal

Title: Biotechnology and Bioengineering

Abbreviated Title: Biotechnology and Bioengineering

Publisher: Wiley

ISSN: 00063592

Publication date Created: January 2019

Publication date (Print): January 2019

Publication date (Electronic): October 27 2018

Volume: 116

Issue: 1

Pages: 206-226

Affiliations

[1 ]Health Sciences Research Centre, Universidade da Beira Interior (CICS-UBI); Covilhã Portugal

[2 ]Departamento de Engenharia Química; Universidade de Coimbra, (CIEPQF); Coimbra Portugal

Article

DOI: 10.1002/bit.26845

PubMed ID: 30367820

SO-VID: 36e6a339-afb8-49db-9447-6c53b74295ec

License:

http://doi.wiley.com/10.1002/tdm_license_1.1

http://onlinelibrary.wiley.com/termsAndConditions#vor

History

Data availability:

Comments

Comment on this article

Cited by 238

See all cited by

Most referenced authors 2,623

See all reference authors

3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs : NUNES et al.

Read this article at