Evidence map›Paper›PMID 36388985›Full record

ArticleiScience2022

Reciprocal effects of mTOR inhibitors on pro-survival proteins dictate therapeutic responses in tuberous sclerosis complex.

Molly C McNamara, Aaron M Hosios, Margaret E Torrence, Ting Zhao, Cameron Fraser, Meghan Wilkinson, David J Kwiatkowski, Elizabeth P Henske, Chin-Lee Wu, Kristopher A Sarosiek and 2 more

Open access · goldAbstract read
In one paragraph

Article in iScience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.5field-weighted citation impact, top 37% 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

6 citing papers in PubMed, 5 citations in OpenAlex.

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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

12 authors at 2 institutions in 1 country.

Molly C McNamaraDepartment of Molecular Metabolism, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, USA.
Aaron M HosiosDepartment of Molecular Metabolism, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, USA.
Margaret E TorrenceDepartment of Molecular Metabolism, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, USA.
Ting ZhaoDepartment of Urology, Massachusetts General Hospital, Boston, MA, USA.
Cameron FraserDepartment of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02215, USA.
Meghan WilkinsonDepartment of Molecular Metabolism, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, USA.
David J KwiatkowskiDivision of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Elizabeth P HenskeDivision of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Chin-Lee WuDepartment of Urology, Massachusetts General Hospital, Boston, MA, USA.
Kristopher A SarosiekDepartment of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02215, USA.
Alexander J ValvezanDepartment of Molecular Metabolism, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, USA.
Brendan D ManningDepartment of Molecular Metabolism, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, USA.
Harvard University · USBrigham and Women's Hospital · US

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI JENNIFER W MACK · 1985 to 2026
$330.6M
Tuberous Sclerosis-Pathway and PathogenesisP01CA120964 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI David J. Kwiatkowski · 2007 to 2026
$35.9M
Decoding and Targeting the PI3K-mTOR Signaling Network in CancerR35CA197459 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI BRENDAN D. MANNING · 2015 to 2026
$10.8M
Interdisciplinary Training in Genes and the EnvironmentT32ES016645 · NIEHS · HARVARD SCHOOL OF PUBLIC HEALTH · PI LEE, CHIH-HAO · 2008 to 2018
$4.0M
Developmental regulation of apoptosis as a modifiable driver of radiotherapy-induced neurocognitive impairment in pediatric patientsR37CA248565 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Kristopher Andrew Sarosiek · 2020 to 2026
$2.6M
Identifying targetable apoptotic vulnerabilities for the treatment of AL amyloidosisR01DK125263 · NIDDK · HARVARD SCHOOL OF PUBLIC HEALTH · PI SAROSIEK, KRISTOPHER ANDREW · 2020 to 2023
$1.4M
NCI NIH HHS P01 CA120964NCI NIH HHS P30 CA006516NCI NIH HHS R35 CA197459NCI NIH HHS R37 CA248565NIDDK NIH HHS R01 DK125263NIEHS NIH HHS T32 ES016645
6 · The paper itself

Abstract

mTORC1 is aberrantly activated in cancer and in the genetic tumor syndrome tuberous sclerosis complex (TSC), which is caused by loss-of-function mutations in the TSC complex, a negative regulator of mTORC1. Clinically approved mTORC1 inhibitors, such as rapamycin, elicit a cytostatic effect that fails to eliminate tumors and is rapidly reversible. We sought to determine the effects of mTORC1 on the core regulators of intrinsic apoptosis. In TSC2-deficient cells and tumors, we find that mTORC1 inhibitors shift cellular dependence from MCL-1 to BCL-2 and BCL-X

Indexed as

Biological sciencesCancerCell biologyMolecular biology

Identifiers

PMID36388985
PMCPMC9663903
OpenAlexW4307726768

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.