scholarly journals Modeling adaptive drug resistance of colorectal cancer and therapeutic interventions with tumor spheroids

2021 ◽  
pp. 153537022110141
Author(s):  
Astha Lamichhane ◽  
Pradip Shahi Thakuri ◽  
Pouria Rafsanjani Nejad ◽  
Hossein Tavana
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Tumor Biology ◽  
Three Dimensional ◽  
Therapeutic Interventions ◽  
Cancer Drug ◽  
Tumor Spheroids ◽  
Major Barrier ◽  
Cancer Drug Discovery ◽  
Cancer Drug Resistance

Drug resistance is a major barrier against successful treatments of cancer patients. Various intrinsic mechanisms and adaptive responses of tumor cells to cancer drugs often lead to failure of treatments and tumor relapse. Understanding mechanisms of cancer drug resistance is critical to develop effective treatments with sustained anti-tumor effects. Three-dimensional cultures of cancer cells known as spheroids present a biologically relevant model of avascular tumors and have been increasingly incorporated in tumor biology and cancer drug discovery studies. In this review, we discuss several recent studies from our group that utilized colorectal tumor spheroids to investigate responses of cancer cells to cytotoxic and molecularly targeted drugs and uncover mechanisms of drug resistance. We highlight our findings from both short-term, one-time treatments and long-term, cyclic treatments of tumor spheroids and discuss mechanisms of adaptation of cancer cells to the treatments. Guided by mechanisms of resistance, we demonstrate the feasibility of designing specific drug combinations to effectively block growth and resistance of cancer cells in spheroid cultures. Finally, we conclude with our perspectives on the utility of three-dimensional tumor models and their shortcomings and advantages for phenotypic and mechanistic studies of cancer drug resistance.

scholarly journals The role of photodynamic therapy in overcoming cancer drug resistance

2015 ◽  
Vol 14 (8) ◽  
pp. 1476-1491 ◽  
Author(s):  
Bryan Q. Spring ◽  
Imran Rizvi ◽  
Nan Xu ◽  
Tayyaba Hasan
Keyword(s):  
Drug Resistance ◽  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Cancer Drug ◽  
Cancer Drug Resistance

This perspective highlights unique mechanisms of photodynamic therapy (PDT) that can be utilized to overcome classical drug resistance and re-sensitize resistant cancer cells for standard therapies.

Analysis of the differences in the Expression of mRNAs and miRNAs Asso-ciated with Drug Resistance in Endometrial Cancer Cells Treated with Salinomycin

2020 ◽  
Vol 21 ◽  
Author(s):  
Piotr Januszyk ◽  
Krzysztof Januszyk ◽  
Magdalena Wierzbik-Strońska ◽  
Dariusz Boroń ◽  
Beniamin Grabarek
Keyword(s):  
Drug Resistance ◽  
Endometrial Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Cancer Cell Line ◽  
Control Culture ◽  
New Drugs ◽  
Cancer Drug ◽  
Cancer Drug Resistance ◽  
Expression Of Genes

Background: It is important to understand the molecular mechanisms involved in cancer drug resistance and to study the activity of new drugs, e.g. salinomycin. Objective: The purpose of the study was to analyze changes in the expression of genes associated with drug resistance in the Ishikawa endometrial cancer cell line when treated with salinomycin. In addition, changes in the level of miRNA potentially regulating these mRNAs were evaluated. Results: The following was observed about the number of mRNAs differentiating the cell culture exposed to the drug compared to a control culture: H-12 vs C - 9 mRNAs, H_24 vs C – 6 mRNAs, H_48 vs C - 1 mRNA. It was noted that 4 of the 9 differentiating mRNAs were characteristic for 12 hours of exposure to the salinomycin and they correspond to the following genes: TUFT1, ABCB1, MTMR11, MX2. After 24 hours, 2 mRNAs were characteristic for this time of incubation cells with salinomycin: TUFT1, MYD88 and after 48 hours, SLC30A5 could also be observed. The highest differences in expression were indicated for TUFT1, MTMR11, SLC30A5. The highest influence probability was determined between TUFT1 and hsamiR-3188 (FC + 2.48), MTMR11and has-miR-16 (FC -1.74), and between SLC30A5 and hsa-miR-30d (FC -2.01). Materials and Methods: Endometrial cancer cells were treated with 1 µM of salinomycin for 12, 24 and 48 hour periods. Untreated cells were a control culture. The molecular analysis consists of mRNA and miRNA microarray analysis and the RTqPCR technique. Conclusions: Salinomycin induces changes in the activity of mRNA and miRNA participating in drug resistance, however the observed changes in character are an expected result of anti-cancer treatment.

scholarly journals Sensitization of Drug Resistant Cancer Cells: A Matter of Combination Therapy

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 483 ◽  
Author(s):  
Meghan Leary ◽  
Sarah Heerboth ◽  
Karolina Lapinska ◽  
Sibaji Sarkar
Keyword(s):  
Drug Resistance ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Progenitor Cells ◽  
Rational Design ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Combination Therapies ◽  
Cancer Drug Resistance ◽  
Rational Development

Cancer drug resistance is an enormous problem. It is responsible for most relapses in cancer patients following apparent remission after successful therapy. Understanding cancer relapse requires an understanding of the processes underlying cancer drug resistance. This article discusses the causes of cancer drug resistance, the current combination therapies, and the problems with the combination therapies. The rational design of combination therapy is warranted to improve the efficacy. These processes must be addressed by finding ways to sensitize the drug-resistant cancers cells to chemotherapy, and to prevent formation of drug resistant cancer cells. It is also necessary to prevent the formation of cancer progenitor cells by epigenetic mechanisms, as cancer progenitor cells are insensitive to standard therapies. In this article, we emphasize the role for the rational development of combination therapy, including epigenetic drugs, in achieving these goals.

scholarly journals Clinically-Relevant ABC Transporter for Anti-Cancer Drug Resistance

2021 ◽  
Vol 12 ◽  
Author(s):  
Huan Xiao ◽  
Yongcheng Zheng ◽  
Lingling Ma ◽  
Lili Tian ◽  
Qiu Sun
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Multiple Drug Resistance ◽  
Cancer Drug ◽  
Multiple Drug ◽  
Cancer Drug Resistance ◽  
Response To Chemotherapy ◽  
New Compounds

Multiple drug resistance (MDR), referring to the resistance of cancer cells to a broad spectrum of structurally and mechanistically unrelated drugs across membranes, severely impairs the response to chemotherapy and leads to chemotherapy failure. Overexpression of ATP binding cassette (ABC) transporters is a major contributing factor resulting in MDR, which can recognize and mediate the efflux of diverse drugs from cancer cells, thereby decreasing intracellular drug concentration. Therefore, modulators of ABC transporter could be used in combination with standard chemotherapeutic anticancer drugs to augment the therapeutic efficacy. This review summarizes the recent advances of important cancer-related ABC transporters, focusing on their physiological functions, structures, and the development of new compounds as ABC transporter inhibitors.

scholarly journals The role of polyphenols in overcoming cancer drug resistance: a comprehensive review

2022 ◽  
Vol 27 (1) ◽  
Author(s):  
Parisa Maleki Dana ◽  
Fatemeh Sadoughi ◽  
Zatollah Asemi ◽  
Bahman Yousefi
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Radical Scavenging ◽  
Epigallocatechin Gallate ◽  
Chemotherapeutic Agents ◽  
Drug Uptake ◽  
Cancer Drug ◽  
Cancer Drug Resistance ◽  
Glutathione S Transferases

AbstractChemotherapeutic drugs are used to treat advanced stages of cancer or following surgery. However, cancers often develop resistance against drugs, leading to failure of treatment and recurrence of the disease. Polyphenols are a family of organic compounds with more than 10,000 members which have a three-membered flavan ring system in common. These natural compounds are known for their beneficial properties, such as free radical scavenging, decreasing oxidative stress, and modulating inflammation. Herein, we discuss the role of polyphenols (mainly curcumin, resveratrol, and epigallocatechin gallate [EGCG]) in different aspects of cancer drug resistance. Increasing drug uptake by tumor cells, decreasing drug metabolism by enzymes (e.g. cytochromes and glutathione-S-transferases), and reducing drug efflux are some of the mechanisms by which polyphenols increase the sensitivity of cancer cells to chemotherapeutic agents. Polyphenols also affect other targets for overcoming chemoresistance in cancer cells, including cell death (i.e. autophagy and apoptosis), EMT, ROS, DNA repair processes, cancer stem cells, and epigenetics (e.g. miRNAs).

Sign in / Sign up

Export Citation Format

Share Document