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NIH Research Festival

September 12 – 14, 2018

Signaling pathway screening platforms are an efficient approach to identify therapeutic targets in cancers that lack known driver mutations

Wednesday, September 12, 2018 – Poster Session II
3:30 – 5:00 p.m.

FAES Terrace

NCI

CANCER-2

Authors

  • E An
  • P Torres-Ayuso
  • J Brognard

Abstract

Precision medicine aims to tailor cancer therapies to target specific tumor promoting aberrations. For tumors that lack actionable drivers, which occurs frequently in the clinic and is major hurdle to matching patients with targeted therapies, extensive molecular characterization and pre-clinical drug efficacy studies will be required. A cell line maintained at low passage and a patient derived xenograft model (PDX) were generated using a fresh biopsy from a patient with a poorly-differentiated neuroendocrine tumor of unknown primary origin. Next-generation sequencing, high throughput signaling network analysis, and drug efficacy trials were then conducted to identify actionable targets for therapeutic intervention. No actionable mutations were identified after whole exome sequencing of the patient’s DNA. However, whole genome sequencing revealed amplification of the 3q and 5p chromosomal arms, that include the PIK3CA and RICTOR genes, respectively. We then conducted pathway analysis, which revealed activation of the AKT pathway. Based on this analysis, the efficacy of PIK3CA and AKT inhibitors were evaluated in the tumor biopsy-derived cell culture and PDX, and response to the AKT inhibitor AZD5363 was observed both in vitro and in vivo indicating the patient would benefit from targeted therapies directed against the serine/threonine kinase AKT. In conclusion, our study demonstrates that high throughput signaling pathway analysis will significantly aid in identifying actionable alterations in rare tumors and guide patient stratification into early-phase clinical trials.

Scientific Focus Area: Cancer Biology

This page was last updated on Friday, March 26, 2021

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Download the 2018 Research Festival Schedule Overview (6 pages)

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Current Research Festival

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  • 2024
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    • Special Wednesday Events
    • Vendor Exhibit Information
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  • 2023
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    • NIH Early–Career Investigator Lectures
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    • General Schedule of Events
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    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
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  • 2018
    • General Schedule of Events
    • Plenary Sessions
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    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
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