Related Experiment Video

Updated: Feb 9, 2026

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

14.4K

Supermolecular drug challenge to overcome drug resistance in cancer cells

Yasuhiko Onishi1, Yuki Eshita2, Rui-Cheng Ji3

  • 1Ryujyu Science Corporation, 39-4 Kosora-cho, Seto, Aichi 489-0842, Japan.

Drug Discovery Today
|June 8, 2018
PubMed

Insights

This study shows that stable enzyme-supermolecule complexes effectively overcome multidrug resistance (MDR) in cancer by utilizing allosteric effects for feedback control, addressing limitations of previous approaches.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Multidrug resistance (MDR) in cancer hinders treatment efficacy.
  • Existing strategies like drug delivery systems and particle-cell interactions do not fully address intratumoral heterogeneity.
  • Anti-MDR therapies need to account for drug target alterations, detoxification, and proliferation.

Purpose of the Study:

  • To investigate a novel approach for overcoming cancer multidrug resistance.
  • To demonstrate the efficacy of enzyme-supermolecule (ES) complexes in anti-MDR therapy.
  • To elucidate the mechanism of action involving allosteric effects and feedback control.

Main Methods:

  • Utilizing artificial enzymes as supermolecular complexes.
  • Applying the induced-fit model to explain allosteric effects.
  • Employing the Hill equation's loop transfer function for feedback control analysis.

Main Results:

  • A stable ES complex was formed, demonstrating excellent anti-MDR efficacy and sustainability.
  • The allosteric effect of supermolecular drugs was explained via the induced-fit model.
  • Stable feedback control systems were achieved through the ES complex.

Conclusions:

  • Enzyme-supermolecule complexes offer a promising strategy for overcoming cancer multidrug resistance.
  • The allosteric mechanism provides a robust feedback control system for sustained therapeutic effects.
  • This approach addresses limitations of previous MDR strategies by considering intratumoral heterogeneity implicitly.

More Related Videos

Overcoming Unresponsiveness in Experimental Autoimmune Encephalomyelitis EAE Resistant Mouse Strains by Adoptive Transfer and Antigenic Challenge08:38

Overcoming Unresponsiveness in Experimental Autoimmune Encephalomyelitis EAE Resistant Mouse Strains by Adoptive Transfer and Antigenic Challenge

Published on: April 9, 2012

21.0K
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

7.6K

Related Concept Videos

Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs01:25

Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs

Asthma is a chronic respiratory condition for which new therapeutic avenues, including anti-inflammatory drugs like mast cell stabilizers and anti-IgE treatments, continue to be developed.
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
1.9K
Pharmacokinetics: Drug–Drug Interactions01:25

Pharmacokinetics: Drug–Drug Interactions

Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
454
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...
3.8K
Bioequivalence of Drugs: Drugs with Multiple Indications01:09

Bioequivalence of Drugs: Drugs with Multiple Indications

The concept of therapeutic equivalence (TE) in drugs with multiple indications is complex. A generic drug may be therapeutically equivalent to a brand-name product for one specific indication, but this doesn't necessarily mean it's equivalent for all other indications. Evidence of TE in one patient group and bioequivalence shown in healthy volunteers can support—but not confirm—TE for other indications. However, definitive proof requires individual clinical studies for each...
162
FDA Approved Drugs: Changes to Approved Drugs01:26

FDA Approved Drugs: Changes to Approved Drugs

Post-approval, manufacturers may modify an approved new or generic drug product. Such modifications can encompass alterations in the Active Pharmaceutical Ingredient (API), manufacturing process, formulation, batch size, manufacturing site, and container closure system (FDA Guidance for Industry, April 2004). Often, a drug product may undergo multiple changes.These modifications require careful evaluation to determine their potential impact on the drug product's identity, strength, quality,...
273
Factors Influencing Drug Absorption: Drug Dissolution01:27

Factors Influencing Drug Absorption: Drug Dissolution

The pharmacokinetic journey of drugs from solid oral dosage forms into systemic circulation is multifaceted. It begins with disintegration, a prerequisite ensuring a solid dosage form's subdivision into minute particles. Dissolution occurs next as these granulated entities solubilize in gastrointestinal fluids. This solubilization is crucial for the succeeding stage, permeation, which describes the traversal of the drug across the intestinal membrane and its subsequent entry into the blood...
1.2K