Impact of multicellular tumor spheroids as an in vivo-like tumor model on anticancer drug response

Abstract

The incidence of colorectal cancer is higher in men than in women, amounting to 15% of cancer-related diseases as a whole. As such, undesirable effects, arising from the administration of current chemotherapeutic agents (the FOLFIRI/FOLFOX combinations), which are exerted on the remaining non-cancerous tissues and/or cells, have contributed to the occurrence of resistance to multiple drugs, thus markedly reducing their efficacy. However, the delivery of chemotherapeutic agents may be improved and their action may be more selectively targeted to diseased tissues/cells by means of developing biotechnologies and nano-techniques. Thus, the current focus is on creating biological tissue and related tumor models, by means of three-dimensional (3D) spheres, in an attempt to bridge the gap between results obtained in the pre-clinical phase and promising outcomes obtained in clinical trials. For this purpose, the characterization and use of so-called ‘multicellular tumor spheroids’, may prove to be invaluable. In this study, we focus on describing the efficacy of a model 3D system as compared to the traditional 2D tumor spheres in determining drug response, highlighting a potentially greater effect of the drugs following the encapsulation of respective liposomes. The results obtained demonstrate the successful preparation of a suspension of liposomes loaded with folinic acid, oxaliplatin and 5-fluorouracil (5-FU), and loaded with meso-tetra (4-sulfonatophenyl) porphyrin. Following its use on HT-29 colorectal cancer cells, an important comparative reduction was noted in the viability of the HT-29 cells, demonstrating the efficacy of multicellular tumor spheroids carrying liposomes loaded with therapeutic drugs. These findings indicate that the method of drug encapsulation in liposomes may improve the treatment efficacy of chemotherapeutic agents.

The Current Landscape of 3D In Vitro Tumor Models: What Cancer Hallmarks Are Accessible for Drug Discovery?

“…One important microenvironmental factor that has been extensively explored is tumor hypoxia, which leads to radio‐ and drug resistance in patient's tumors . Typically, studies have involved the use of 2D monolayers in hypoxia chambers, multicellular spheroids, or natural polymer hydrogel slabs confined within microfluidic channels . For example, to search for drugs that reduce tumor hypoxia, potentially acting as modifiers in a clinical setting, Ashton et al performed a screen of 1697 FDA‐approved compounds by monitoring oxygen consumption rate (OCR) in monolayer cancer cell lines .…”

Peripheral Neurotoxicity Induced by Taxanes, Cisplatin, Oxaliplatin, Fluoropyrimidines and Vinorelbine. A clinical perspective

“…It has been demonstrated that the antitumor effect of oxaliplatin administered this way is present. Whether neurotoxicity incidence and grade can Table 3 ANTINEOPLASTIC AGENTS USED IN THE STUDY AND THEIR CHARACTERISTICS [10][11][12][13] be reduced by this type of administration is still a matter of debate [31,32].…”

Does sex of the patient play a role in survival for MSI colorectal cancer?

“…However, when adjuvant tratment containing fluoropyrimidines and oxaliplatin is necessitated, longterm toxicity becomes the main issue. The possibility of targeting cancer cells with these drugs by using liposomes has been recently studied, although the efficacy of this method of administering chemotherapy on toxicity is still a matter of debate (24). Several studies have addressed the role microsatellite instability plays in colorectal cancer patients (25)(26)(27).…”