Related Experiment Video

Updated: Aug 19, 2026

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

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

Reversing resistance to targeted therapy

L Vidal1, G Attard, S Kaye

  • 1Institute of Cancer Research and Royal Marsden Hospital, Sutton, UK.

Journal of Chemotherapy (Florence, Italy)
|February 4, 2005
PubMed

Insights

Molecular targeted anticancer drugs offer new hope, but drug resistance is a challenge. Understanding common resistance mechanisms is key to developing strategies for better patient outcomes.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Molecular targeted anticancer drugs represent a significant advancement in cancer treatment.
  • Drug resistance to these novel therapies is a major clinical obstacle, limiting their long-term efficacy.

Purpose of the Study:

  • To identify and categorize common molecular mechanisms underlying drug resistance to targeted anticancer agents.
  • To highlight the importance of molecular evaluation in understanding and overcoming therapeutic resistance.

Main Methods:

  • Review and synthesis of existing literature on molecular targeted drug resistance.
  • Categorization of resistance mechanisms based on molecular alterations at various biological levels (DNA, mRNA, protein).
  • Emphasis on the role of pharmacokinetics, pharmacogenetics, and pharmacodynamics in resistance.

Main Results:

  • Common resistance mechanisms include inadequate target blockade, altered target expression or structure, modified target regulation, and activation of alternative signaling pathways.
  • Specific examples of targeted agents like hormone therapies, trastuzumab, imatinib, and gefitinib illustrate these mechanisms.
  • Drug resistance is often multifactorial, involving complex molecular interactions.

Conclusions:

  • A comprehensive molecular understanding of drug resistance is crucial for developing effective reversal strategies.
  • Integrating pharmacokinetic, pharmacogenetic, and pharmacodynamic studies will facilitate improved patient outcomes in targeted cancer therapy.
  • Future research should focus on personalized approaches to combatting molecular resistance in cancer treatment.

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

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...
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 specific...
Treatment Resistent Cancers02:56

Treatment Resistent 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...
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...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...