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Related Concept Videos

Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
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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...
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...
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...

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Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers
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Published on: February 20, 2017

Chromosomal instability determines taxane response.

Charles Swanton1, Barbara Nicke, Marion Schuett

  • 1Cancer Research UK, London Research Institute, London WC2A 3PX, United Kingdom.

Proceedings of the National Academy of Sciences of the United States of America
|May 22, 2009
PubMed
Summary
This summary is machine-generated.

Microtubule-stabilizing agents

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Published on: May 14, 2016

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Microtubule-stabilizing (MTS) agents, like taxanes, are crucial chemotherapeutics, but their precise mechanism remains unclear.
  • Genes repressed by MTS agents are overexpressed in tumors with chromosomal instability (CIN).

Purpose of the Study:

  • To investigate the role of specific genes in cancer cell survival and response to MTS agents.
  • To explore the link between chromosomal instability (CIN) and therapeutic outcomes.

Main Methods:

  • Gene expression analysis in cell lines treated with MTS agents.
  • Gene silencing experiments to assess the impact on cancer cell viability.
  • Correlation analysis of gene expression, CIN, and clinical outcomes in breast and ovarian cancer patients.

Main Results:

  • A set of 50 "CIN-survival" genes were identified, with 22 involved in DNA repair.
  • Silencing these genes led to cancer cell death, indicating their role in aneuploid cell survival.
  • Overexpression of CIN-survival genes correlates with poor prognosis in estrogen receptor-positive breast cancer and is frequent in basal-like and Her2-positive subtypes.
  • Paclitaxel repressed CIN-survival genes in diploid cells, causing cell death, but not in chromosomally unstable cells.
  • High CIN levels in ovarian cancer patients predicted resistance to taxanes but sensitivity to carboplatin.

Conclusions:

  • CIN-survival genes are critical for aneuploid cancer cell survival and are implicated in MTS agent resistance.
  • Chromosomal instability (CIN) is a key determinant of response to microtubule-stabilizing agents in vivo.
  • Pretherapeutic assessment of CIN could refine treatment strategies and clinical trial design for MTS agents.