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Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Cancer Chemoresistance; Recent Challenges and Future Considerations
Muhammad Adil1, Shamsa Kanwal2, Sarmad Rasheed2
1Pharmacology and Toxicology Section, University of Veterinary and Animal Sciences, Lahore, Jhang Campus, Jhang, 35200, Pakistan. muhammad.adil@uvas.edu.pk.
Abstract:
Cancer remains one of the serious health hazards and major causes of human mortality across the world. Despite the development of many typical antineoplastic drugs and introduction of novel targeted agents, chemoresistance constitutes a major challenge in the effective therapeutic management of cancer. Drug inactivation, efflux of anticancer agents, modification of target sites, enhanced repair of DNA damage, apoptosis failure and induction of epithelial-mesenchymal transition are the principal mechanisms of cancer chemoresistance. Moreover, epigenetics, cell signaling, tumor heterogeneity, stem cells, microRNAs, endoplasmic reticulum, tumor microenvironment and exosomes have also been implicated in the multifaceted phenomenon of anticancer drug resistance. The tendency of resistance is either intrinsically possessed or subsequently acquired by cancerous cells. From clinical oncology standpoint, therapeutic failure and tumor progression are the most probable consequences of cancer chemoresistance. Combination therapy can help to overcome the issue of drug resistance, and therefore, the development of such treatment regimens is recommended for counteracting the emergence and dissemination of cancer chemoresistance. This chapter outlines the current knowledge on underlying mechanisms, contributory biological factors and likely consequences of cancer chemoresistance. Besides, prognostic biomarkers, diagnostic methods and potential approaches to overcome the emergence of antineoplastic drug resistance have also been described.
Insights
Cancer chemoresistance is a major challenge, driven by complex mechanisms like drug inactivation and epigenetics. Combination therapy offers a promising strategy to overcome drug resistance and improve cancer treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Cancer remains a leading cause of mortality worldwide.
- Chemoresistance significantly hinders effective cancer treatment.
- Understanding chemoresistance mechanisms is crucial for therapeutic advancement.
Purpose of the Study:
- To outline current knowledge on cancer chemoresistance mechanisms.
- To discuss biological factors contributing to drug resistance.
- To explore strategies for overcoming chemoresistance.
Main Methods:
- Literature review of cancer chemoresistance.
- Analysis of molecular and cellular mechanisms.
- Discussion of clinical implications and therapeutic approaches.
Main Results:
- Identified principal mechanisms: drug inactivation, efflux, target modification, DNA repair, apoptosis failure, and epithelial-mesenchymal transition.
- Highlighted roles of epigenetics, cell signaling, tumor microenvironment, and exosomes.
- Emphasized intrinsic and acquired resistance in cancer cells.
Conclusions:
- Chemoresistance leads to therapeutic failure and tumor progression.
- Combination therapy is recommended to combat drug resistance.
- Prognostic biomarkers and diagnostic methods are essential for managing chemoresistance.
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