Related Experiment Video

Updated: May 14, 2026

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

A Comprehensive Gene Expression Analysis of Resistance Formation upon Metronomic Cyclophosphamide Therapy

Rebekka Kubisch1, Lilja Meissner, Stefan Krebs

  • 1Pharmaceutical Biotechnology, Department of Pharmacy, Center for System-Based Drug Research, Ludwig-Maximilians University, Munich, Germany.

Translational Oncology
|February 19, 2013
PubMed

Insights

Cancer treatment resistance can be overcome by understanding molecular changes. This study reveals that altered anti-coagulation pathways are key mechanisms in resistance to metronomic cyclophosphamide (CPA) therapy in prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Resistance to cancer therapy is a significant clinical challenge.
  • Metronomic anti-angiogenic therapy with cyclophosphamide (CPA) can induce resistance in prostate cancer models.
  • Understanding the molecular basis of this resistance is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the comprehensive molecular changes associated with resistance formation during metronomic CPA treatment.
  • To identify key pathways and genes involved in the development of resistant tumors.

Main Methods:

  • Gene expression analysis of resistant xenografted prostate cancer tumors in severe combined-immunodeficiency (SCID) mice.
  • Comparison of gene expression profiles between resistant and sensitive tumor samples.
  • Validation of key gene expression changes using quantitative real-time polymerase chain reaction (qRT-PCR).

Main Results:

  • Numerous differentially expressed genes were identified in resistant tumors, including PAS domain containing protein 1, annexin A3 (ANXA3), neurotensin, and plasminogen activator tissue (PLAT).
  • Significant differences in gene expression were observed between in vivo and in vitro tumor cell conditions.
  • Differentially expressed genes were enriched in pathways such as axon guidance, steroid biosynthesis, and complement and coagulation cascades, with a notable involvement in anti-coagulation.
  • Upregulation of ANXA3 and PLAT, downregulation of their inhibitor, and upregulation of coagulation factor F3 were validated.

Conclusions:

  • Metronomic CPA resistance in prostate cancer involves significant molecular alterations.
  • The complement and coagulation cascade, particularly anti-coagulation mechanisms, play a critical role in the development of resistance.
  • These findings provide insights into resistance mechanisms and suggest potential therapeutic targets.

More Related Videos

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis11:44

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Published on: March 30, 2019

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms08:46

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

Published on: December 9, 2015

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...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

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...