Related Experiment Video

Updated: Jul 19, 2025

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
09:58

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models

Published on: December 9, 2016

13.8K

Nucleoside-based anticancer drugs: Mechanism of action and drug resistance

Lenka Hruba1, Viswanath Das1, Marian Hajduch2

  • 1Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Olomouc, Czech Republic.

Biochemical Pharmacology
|August 11, 2023
PubMed

Insights

Nucleoside-based drugs are vital for treating cancers and viral infections but drug resistance limits their effectiveness. This review details resistance mechanisms and proposes strategies like targeted therapies to overcome them.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Oncology

Background:

  • Nucleoside-based drugs, including purine and pyrimidine analogs, have been mainstays in treating cancers, myelodysplastic syndromes, multiple sclerosis, and viral infections since the 1950s.
  • These antimetabolites exert therapeutic effects through complex interactions with cellular components, often involving phosphorylation cascades and nucleic acid interactions.
  • A significant clinical challenge is the development of drug resistance, which compromises the efficacy of these essential medications.

Purpose of the Study:

  • To comprehensively review the multifaceted mechanisms of resistance to nucleoside-based drugs.
  • To analyze the intricate drug-cell interactions contributing to therapeutic failure.
  • To identify and guide the development of novel strategies to overcome drug resistance and improve patient outcomes.

Main Methods:

  • Literature review and critical analysis of existing research on nucleoside-based drug resistance.
  • Exploration of resistance mechanisms at the cellular and molecular levels, including transport, metabolism, and DNA repair.
  • Synthesis of findings to propose future therapeutic directions.

Main Results:

  • Resistance mechanisms are diverse, involving alterations in membrane transporters, activating kinases, drug elimination pathways, and DNA damage repair.
  • Understanding these complex drug-cell interactions is crucial for predicting and managing resistance.
  • The review highlights specific pathways and molecular targets implicated in nucleoside drug resistance.

Conclusions:

  • Targeted therapies, novel nucleoside analog development, and synergistic drug combinations represent promising strategies to counteract resistance.
  • Restoring tumor sensitivity and enhancing patient outcomes are key goals for future clinical applications.
  • Further research into overcoming drug resistance is essential for maximizing the therapeutic potential of nucleoside-based agents.
Keywords:
ABC transportersCancerCancer therapyDrug resistanceMetabolismNucleosidesSLC transporters

More Related Videos

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

10.6K
Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

7.2K

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.7K
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
6.4K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
5.1K