Modeling ERBB receptor-regulated G1/S transition to find novel targets for de novo trastuzumab resistance
2009

Finding New Targets for Trastuzumab Resistance in Breast Cancer

publication Evidence: moderate

Author Information

Author(s): Sahin Özgür, Fröhlich Holger, Löbke Christian, Korf Ulrike, Burmester Sara, Majety Meher, Mattern Jens, Schupp Ingo, Chaouiya Claudine, Thieffry Denis, Poustka Annemarie, Wiemann Stefan, Beissbarth Tim, Arlt Dorit

Primary Institution: German Cancer Research Center

Hypothesis

Can we identify novel therapeutic targets to overcome de novo trastuzumab resistance in breast cancer?

Conclusion

The study identified c-MYC as a potential target for treating trastuzumab resistant breast cancer, while combinatorial targeting of ERBB receptors was not effective.

Supporting Evidence

  • Combinatorial targeting of ERBB2 and EGFR did not affect the response to trastuzumab in resistant cells.
  • c-MYC perturbation affected both trastuzumab sensitive and resistant cells.
  • Knockdowns of CDK4, Cyclin D1, and Cyclin E1 significantly reduced pRB phosphorylation.

Takeaway

Researchers looked for new ways to treat breast cancer that doesn't respond to a common drug called trastuzumab, and they found that a protein called c-MYC might help.

Methodology

The study combined computational simulations, experimental testing of simulation results, and reverse engineering of a protein interaction network.

Limitations

The model may not account for all interactions and could miss some regulatory effects.

Statistical Information

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1186/1752-0509-3-1

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