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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...
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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...
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Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
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Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
Desensitization and Tachyphylaxis01:20

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Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
Several...
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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.
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Updated: May 15, 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

Smoothing out drug resistance.

Maria Kasper1, Rune Toftgård

  • 1Karolinska Institutet, Center for Biosciences and Department of Biosciences and Nutrition, Novum, Huddinge, Sweden.

Cancer Cell
|January 19, 2013
PubMed
Summary
This summary is machine-generated.

Smoothened inhibitors treat Hedgehog pathway tumors but cause drug resistance. Combining itraconazole and arsenic trioxide overcomes this resistance, offering new therapeutic options for these cancers.

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Last Updated: May 15, 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

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype
14:51

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Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

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

Published on: December 9, 2015

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Hedgehog pathway signaling is crucial for the development and progression of various cancers.
  • Smoothened inhibitors are effective against Hedgehog pathway-dependent tumors but often encounter acquired drug resistance.
  • Drug resistance limits the long-term efficacy of targeted cancer therapies.

Discussion:

  • Acquired resistance to smoothened inhibitors is a significant clinical challenge.
  • Combining existing drugs like itraconazole and arsenic trioxide can overcome specific resistance mechanisms.
  • This combination strategy offers a potential new therapeutic avenue for refractory tumors.

Key Insights:

  • A novel drug combination of itraconazole and arsenic trioxide effectively targets Hedgehog pathway-dependent tumors.
  • This approach demonstrates efficacy in overcoming acquired resistance to smoothened inhibitors.
  • The study provides a potential strategy to re-sensitize resistant tumors to therapy.

Outlook:

  • Further clinical investigation is warranted to evaluate the safety and efficacy of this combination therapy.
  • This research may pave the way for developing new treatment protocols for resistant cancers.
  • Exploring combination therapies is a promising direction for improving outcomes in oncology.