Evidence map›Paper›PMID 30266815›Full record

ArticleCancer discovery2019

Genome-Informed Targeted Therapy for Osteosarcoma.

Leanne C Sayles, Marcus R Breese, Amanda L Koehne, Stanley G Leung, Alex G Lee, Heng-Yi Liu, Aviv Spillinger, Avanthi T Shah, Bogdan Tanasa, Krystal Straessler and 11 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 291 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
291citing papers in PubMed, 1 pooled it
10.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

291 citing papers in PubMed, 1 synthesis or guideline pooled it, 449 citations in OpenAlex.

  1. Biological Sample Collection to Advance Research and Treatment: A Fight Osteosarcoma Through European Research and Euro Ewing Consortium Statement.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
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231 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 5 institutions in 1 country.

Leanne C Sayles *Division of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, California.
Marcus R Breese *Division of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, California.
Amanda L KoehneDivision of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, California.
Stanley G LeungDivision of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, California.
Alex G LeeDivision of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, California.
Heng-Yi LiuDivision of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, California.
Aviv SpillingerDivision of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, California.
Avanthi T ShahDivision of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, California.
Bogdan TanasaDivision of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, California.
Krystal StraesslerDivision of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, California.
Florette K HazardDepartment of Pathology, Stanford University School of Medicine, Stanford University, Stanford, California.
Sheri L SpuntDivision of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, Stanford University, Stanford, California.
Neyssa MarinaDivision of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, Stanford University, Stanford, California.
Grace E KimDepartment of Pathology, University of California, San Francisco, California.ORCID 0000-0002-7712-3653
Soo-Jin ChoDepartment of Pathology, University of California, San Francisco, California.
Raffi S AvedianDepartment of Orthopedic Surgery, Stanford University School of Medicine, Stanford University, Stanford, California.
David G MohlerDepartment of Orthopedic Surgery, Stanford University School of Medicine, Stanford University, Stanford, California.
Mi-Ok KimBiostatistics Core, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.ORCID 0000-0002-7712-3653
Steven G DuBoisDana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, Massachusetts.
Douglas S HawkinsSeattle Children's Hospital, University of Washington, Fred Hutchison Cancer Research Center, Seattle, Washington.
E Alejandro Sweet-CorderoDivision of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, California. Alejandro.Sweet-Cordero@ucsf.edu.
University of California, San Francisco · USStanford University · USBiostatistical Consulting (United States) · USDana-Farber/Boston Children's Cancer and Blood Disorders Center · USSeattle Children's Hospital · US

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer Leigh Clarke · 1999 to 2026
$209.7M
Comparative Medicine Biosciences Training ProgramT32OD011121 · OD · STANFORD UNIVERSITY · PI BUCKMASTER, PAUL S. · 2012 to 2025
$3.2M
Cancer Systems Biology Scholars ProgramR25CA180993 · NCI · STANFORD UNIVERSITY · PI PLEVRITIS, SYLVIA KATINA · 2014 to 2018
$2.2M
Mechanisms of chemotherapy response and tumor re-initiation in lung cancerR01CA157510 · NCI · STANFORD UNIVERSITY · PI SWEET-CORDERO, ERIC ALEJANDRO · 2011 to 2015
$1.7M
High Throughput DNA Sequencer UpgradeS10OD018220 · OD · STANFORD UNIVERSITY · PI COLLER, JOHN · 2014 to 2014
$596k
NCI NIH HHS P30 CA082103NCI NIH HHS R01 CA157510NCI NIH HHS R25 CA180993NIH HHS S10 OD018220NIH HHS T32 OD011121
6 · The paper itself

Abstract

Osteosarcoma is a highly aggressive cancer for which treatment has remained essentially unchanged for more than 30 years. Osteosarcoma is characterized by widespread and recurrent somatic copy-number alterations (SCNA) and structural rearrangements. In contrast, few recurrent point mutations in protein-coding genes have been identified, suggesting that genes within SCNAs are key oncogenic drivers in this disease. SCNAs and structural rearrangements are highly heterogeneous across osteosarcoma cases, suggesting the need for a genome-informed approach to targeted therapy. To identify patient-specific candidate drivers, we used a simple heuristic based on degree and rank order of copy-number amplification (identified by whole-genome sequencing) and changes in gene expression as identified by RNA sequencing. Using patient-derived tumor xenografts, we demonstrate that targeting of patient-specific SCNAs leads to significant decrease in tumor burden, providing a road map for genome-informed treatment of osteosarcoma. SIGNIFICANCE: Osteosarcoma is treated with a chemotherapy regimen established 30 years ago. Although osteosarcoma is genomically complex, we hypothesized that tumor-specific dependencies could be identified within SCNAs. Using patient-derived tumor xenografts, we found a high degree of response for "genome-matched" therapies, demonstrating the utility of a targeted genome-informed approach.

Indexed as

Genomic Structural VariationMolecular Targeted TherapyAnimalsBone NeoplasmsDNA Copy Number VariationsGenomicsHumansMiceOsteosarcomaSequence Analysis, RNAWhole Genome SequencingXenograft Model Antitumor Assays

Identifiers

PMID30266815
PMCPMC7134333
OpenAlexW2892650455

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.