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Related Concept Videos

Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...
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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Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...
Development of Antibiotic Resistance01:30

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Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
Combined Effects of Drugs: Synergism01:27

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Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Antibiotic Selection00:57

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Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
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Is resistance useless? Multidrug resistance and collateral sensitivity.

Matthew D Hall1, Misty D Handley, Michael M Gottesman

  • 1Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Trends in Pharmacological Sciences
|September 19, 2009
PubMed
Summary

Cancer cells resistant to chemotherapy via P-glycoprotein (P-gp) can become sensitive to other drugs, a phenomenon called collateral sensitivity. Exploiting this collateral sensitivity may improve cancer treatment outcomes.

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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:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Multidrug resistance (MDR) in cancer is often mediated by P-glycoprotein (P-gp), an efflux pump conferring resistance to various chemotherapeutics.
  • P-gp expression leads to cross-resistance, limiting treatment efficacy and posing a significant clinical challenge.
  • Existing strategies to overcome MDR have yielded limited clinical success over the past three decades.

Purpose of the Study:

  • To review the phenomenon of collateral sensitivity (CS) in MDR cancer cells.
  • To explore underlying mechanisms, such as reactive oxygen species generation, contributing to CS.
  • To propose CS as a viable strategy for enhancing chemotherapy response.

Main Methods:

  • Literature review of studies investigating MDR and CS in cancer.
  • Analysis of proposed molecular mechanisms for collateral sensitivity.
  • Synthesis of findings to propose therapeutic strategies.

Main Results:

  • MDR cancer cells exhibit hypersensitivity to certain drugs, a phenomenon termed collateral sensitivity (CS).
  • CS is a widespread effect in P-gp-mediated multidrug resistance.
  • Hypotheses regarding the generality of CS include the role of reactive oxygen species.

Conclusions:

  • Collateral sensitivity represents a significant, yet underexplored, aspect of multidrug resistance.
  • Understanding the mechanisms of CS can provide novel therapeutic avenues.
  • Exploiting collateral sensitivity offers a promising strategy to improve chemotherapy effectiveness in resistant cancers.