Evidence map›Paper›PMID 31521127›Full record

ArticleBMC cancer2019

Smac mimetics LCL161 and GDC-0152 inhibit osteosarcoma growth and metastasis in mice.

Tanmay M Shekhar, Ingrid J G Burvenich, Michael A Harris, Angela Rigopoulos, Damien Zanker, Alex Spurling, Belinda S Parker, Carl R Walkley, Andrew M Scott, Christine J Hawkins

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

Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

20 citing papers in PubMed, 32 citations in OpenAlex.

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  7. Recent and Ongoing Research into Metastatic Osteosarcoma Treatments.International journal of molecular sciences · 2022
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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

10 authors at 2 institutions in 1 country.

Tanmay M ShekharDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, 3086, Australia.
Ingrid J G BurvenichTumour Targeting Laboratory, Ludwig Institute for Cancer Research and Olivia Newton-John Cancer Research Institute, Melbourne, Australia.
Michael A HarrisDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, 3086, Australia.
Angela RigopoulosTumour Targeting Laboratory, Ludwig Institute for Cancer Research and Olivia Newton-John Cancer Research Institute, Melbourne, Australia.
Damien ZankerDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, 3086, Australia.
Alex SpurlingDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, 3086, Australia.
Belinda S ParkerDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, 3086, Australia.
Carl R WalkleySt. Vincent's Institute, Fitzroy, Victoria, 3065, Australia.
Andrew M ScottTumour Targeting Laboratory, Ludwig Institute for Cancer Research and Olivia Newton-John Cancer Research Institute, Melbourne, Australia.
Christine J HawkinsDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, 3086, Australia. c.hawkins@latrobe.edu.au.ORCID http://orcid.org/0000-0001-8120-1071
La Trobe University · AUThe University of Melbourne · AU

Funding

Australasian Sarcoma Study Group N/ACancer Council Victoria APP1145995The Kids' Cancer Project N/A
6 · The paper itself

Abstract

backgroundCurrent therapies fail to cure over a third of osteosarcoma patients and around three quarters of those with metastatic disease. "Smac mimetics" (also known as "IAP antagonists") are a new class of anti-cancer agents. Previous work revealed that cells from murine osteosarcomas were efficiently sensitized by physiologically achievable concentrations of some Smac mimetics (including GDC-0152 and LCL161) to killing by the inflammatory cytokine TNFα in vitro, but survived exposure to Smac mimetics as sole agents.

methodsNude mice were subcutaneously or intramuscularly implanted with luciferase-expressing murine 1029H or human KRIB osteosarcoma cells. The impacts of treatment with GDC-0152, LCL161 and/or doxorubicin were assessed by caliper measurements, bioluminescence,

resultsTreatment with GDC-0152 or LCL161 suppressed the growth of subcutaneously or intramuscularly implanted osteosarcomas. In both models, co-treatment with doxorubicin and Smac mimetics impeded average osteosarcoma growth to a greater extent than either drug alone, although these differences were not statistically significant. Co-treatments were also more toxic. Co-treatment with LCL161 and doxorubicin was particularly effective in the KRIB intramuscular model, impeding primary tumor growth and delaying or preventing metastasis. Although the Smac mimetics were effective in vivo, in vitro they only efficiently killed osteosarcoma cells when TNFα was supplied. Implanted tumors contained high levels of TNFα, produced by infiltrating immune cells. Spontaneous osteosarcomas that arose in genetically-engineered immunocompetent mice also contained abundant TNFα.

conclusionsThese data imply that Smac mimetics can cooperate with TNFα secreted by tumor-associated immune cells to kill osteosarcoma cells in vivo. Smac mimetics may therefore benefit osteosarcoma patients whose tumors contain Smac mimetic-responsive cancer cells and TNFα-producing infiltrating cells.

Indexed as

AnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell ProliferationCyclohexanesDisease Models, AnimalHumansMagnetic Resonance ImagingMiceNeoplasmsPositron-Emission TomographyPyrrolesThiazolesXenograft Model Antitumor AssaysAntineoplastic AgentsCyclohexanesGDC-0152LCL161PyrrolesThiazolesAnthracyclineBone cancerIAP antagonistMetastasisMouse cancer modelOsteosarcomaSarcomaSmac mimeticTargeted therapy

Identifiers

PMID31521127
PMCPMC6744692
OpenAlexW2972932003

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.