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The multi-factorial nature of clinical multidrug resistance in cancer
- Source :
- Drug Resistance Updates
- Publication Year :
- 2019
-
Abstract
- Curative cancer therapy remains a major challenge particularly in cancers displaying multidrug resistance (MDR). The MDR phenotype is characterized by cross-resistance to a wide array of anticancer drugs harboring distinct structures and mechanisms of action. The multiple factors involved in mediating MDR may include host factors, tumor factors as well as tumor-host interactions. Among the host factors are genetic variants and drug-drug interactions. The plethora of tumor factors involves decreased diminished drug uptake primarily via impaired influx transporters, increased drug efflux predominantly due to the overexpression of multidrug efflux transporters of the ATP-binding cassette superfamily or due to drug efflux mediated by extracellular vesicles or drug-loaded lysosomes undergoing exocytosis, drug metabolism, deregulation of cell death mechanisms (i.e. anti-apoptotic modalities), enhanced DNA damage repair, epigenetic alterations and/or deregulation in microRNAs. The intratumor heterogeneity and dynamics, along with cancer stem cell plasticity, are important tumor factors. Among the tumor-host interactions are the role of the tumor microenvironment, selection pressures of various stressor conditions and agents, acidic pH and the intracellular transfer of traits mediated by extracellular vesicles. The involvement of these diverse factors in MDR highlights the need for precision medicine and real-time personalized treatments of individual cancer patients. In this review, written by a group of researchers from COST Action STRATAGEM “New diagnostic and therapeutic tools against multidrug resistant tumors”, we aim to bring together these multidisciplinary and interdisciplinary features of MDR cancers. Importantly, it is becoming increasingly clear that deciphering the molecular mechanisms underlying anticancer drug resistance, will pave the way towards the development of novel precision medicine treatment modalities that are able to surmount distinct mechanisms of anticancer drug resistance.
- Subjects :
- 0301 basic medicine
Drug
Cancer Research
cancer
clinical multidrug resistance
cancer patients
genetic variants
drug-drug interactions
drug efflux
drug compartmentalization
extracellular vesicles
cell death mechanisms
DNA damage response and repair
epigenetic
microRNAs
intratumor heterogeneity and dynamics
stem cell plasticity
tumor microenvironment
selection pressures
acidic environment
precision medicine
media_common.quotation_subject
Antineoplastic Agents
Biology
03 medical and health sciences
0302 clinical medicine
Cancer stem cell
Neoplasms
Clinical Medical Sciences
Tumor Microenvironment
medicine
Humans
Drug Interactions
Pharmacology (medical)
Epigenetics
media_common
Pharmacology
Tumor microenvironment
Cancer
Biological Transport
Basic Medical Sciences
Precision medicine
medicine.disease
Drug Resistance, Multiple
3. Good health
Multiple drug resistance
030104 developmental biology
Infectious Diseases
Oncology
Drug Resistance, Neoplasm
BIOMEDICINE AND HEALTHCARE
030220 oncology & carcinogenesis
Neoplastic Stem Cells
Cancer research
Efflux
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Drug Resistance Updates
- Accession number :
- edsair.doi.dedup.....1dbdee1d57115ff04d702af777aff443