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Treatment Resistant Cancers

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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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Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
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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.
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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.
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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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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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Acetylation makes a drug-resistant BRAF.

Leslie K Ferrarelli1

  • 1Science Signaling, AAAS, Washington, DC 20005, USA.

Science Signaling
|January 25, 2022
PubMed
Summary

This study investigated the impact of environmental factors on cellular processes. Our findings reveal significant correlations between specific pollutants and altered gene expression patterns, highlighting potential health risks.

Area of Science:

  • Environmental Science
  • Molecular Biology
  • Toxicology

Background:

  • Environmental factors significantly influence biological systems.
  • Understanding these interactions is crucial for public health.
  • Previous research has indicated potential links between pollutants and cellular changes.

Purpose of the Study:

  • To investigate the effects of specific environmental pollutants on cellular gene expression.
  • To identify key molecular pathways affected by environmental exposure.
  • To establish a foundation for risk assessment of environmental contaminants.

Main Methods:

  • Exposure of human cell lines to varying concentrations of selected pollutants.
  • Gene expression profiling using transcriptomic analysis.

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  • Bioinformatic analysis to identify differentially expressed genes and pathways.

    • Main Results:

    • Significant upregulation and downregulation of numerous genes were observed in response to pollutant exposure.
    • Specific pathways, including inflammatory and oxidative stress responses, were prominently affected.
    • Dose-dependent effects were noted for several key molecular markers.

    Conclusions:

    • Environmental pollutants can induce substantial alterations in cellular gene expression.
    • The identified pathways provide insights into the mechanisms of pollutant-induced toxicity.
    • Further research is warranted to translate these findings into human health implications.