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Microscaled proteogenomic methods for precision oncology.

Shankha Satpathy1, Eric J Jaehnig2, Karsten Krug3

  • 1Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, 02142, USA. shankha@broadinstitute.org.

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|January 29, 2020
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Summary
This summary is machine-generated.

This study introduces a new proteogenomics method for small cancer biopsies, enabling detailed analysis of ERBB2 positive breast cancer treatment response and resistance mechanisms.

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Area of Science:

  • Proteomics
  • Genomics
  • Cancer Biology

Background:

  • Proteogenomics integrates multi-omics data for cancer insights.
  • Current methods require large sample inputs, limiting clinical application.

Purpose of the Study:

  • To develop and demonstrate a tissue-sparing proteogenomics approach for core biopsies.
  • To analyze ERBB2 positive breast cancer response to neoadjuvant chemotherapy.

Main Methods:

  • Developed a microscaled proteomics workflow for core needle biopsies.
  • Analyzed ERBB2 positive breast cancer biopsies before and after trastuzumab therapy.

Main Results:

  • Observed greater ERBB2 and mTOR pathway suppression in complete responders.
  • Identified resistance mechanisms including lack of ERBB2 amplification, androgen receptor signaling, mucin overexpression, and an inactive immune microenvironment.

Conclusions:

  • Biopsy-scale proteogenomics is clinically valuable and facilitates discovery.
  • This approach can reveal mechanisms of treatment resistance in breast cancer.