Evidence map›Paper›PMID 35931701›Full record

ArticleCell death & disease2022

AL101, a gamma-secretase inhibitor, has potent antitumor activity against adenoid cystic carcinoma with activated NOTCH signaling.

Renata Ferrarotto, Vasudha Mishra, Elad Herz, Adar Yaacov, Oz Solomon, Rami Rauch, Adi Mondshine, Maria Motin, Tal Leibovich-Rivkin, Matti Davis and 10 more

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

Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.4field-weighted citation impact, top 6% 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

31 citing papers in PubMed, 39 citations in OpenAlex.

  1. SMURF2 in Anticancer Therapy: Dual Role in Carcinogenesis and Theranostics.International journal of molecular sciences · 2026
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  16. Prognostic factors for development of distant metastases in surgically treated high-grade salivary gland carcinomas: results of retrospective single center study with 213 patients.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2024
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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

20 authors at 4 institutions in 1 country.

Renata Ferrarotto *Department of Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Vasudha Mishra *Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Elad HerzAyala Pharmaceuticals, Rehovot, Israel.
Adar YaacovAyala Pharmaceuticals, Rehovot, Israel.ORCID 0000-0002-6106-2307
Oz SolomonAyala Pharmaceuticals, Rehovot, Israel.ORCID 0000-0003-3325-0332
Rami RauchAyala Pharmaceuticals, Rehovot, Israel.
Adi MondshineAyala Pharmaceuticals, Rehovot, Israel.
Maria MotinAyala Pharmaceuticals, Rehovot, Israel.
Tal Leibovich-RivkinAyala Pharmaceuticals, Rehovot, Israel.
Matti DavisAyala Pharmaceuticals, Rehovot, Israel.
Joel KayeAyala Pharmaceuticals, Rehovot, Israel.
Christopher R WeberDepartment of Pathology, University of Chicago, Chicago, IL, USA.
Le ShenDepartment of Pathology, University of Chicago, Chicago, IL, USA.
Alexander T PearsonDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Ari J RosenbergDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Xiangying ChenDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Alka SinghDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Jon C AsterDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Nishant AgrawalDepartment of Surgery, Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, IL, USA.ORCID 0000-0002-1361-3231
Evgeny IzumchenkoDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA. izumchen@uchicago.edu.ORCID 0000-0003-3500-5664
University of Chicago · USBrigham and Women's Hospital · USThe University of Texas MD Anderson Cancer Center · USUniversity of Illinois Chicago · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Delineating chromatin-related gene expression signatures as a function of HNSCC progressionR01DE027809 · NIDCR · UNIVERSITY OF MARYLAND BALTIMORE · PI GAYKALOVA, DARIA A, IZUMCHENKO, EVGENY (EUGENE) G · 2019 to 2023
$2.6M
Somatic Mutations in Tissue and Saliva as Prognostic and Screening Biomarkers for Oral PremalignancyR01DE028674 · NIDCR · UNIVERSITY OF CHICAGO · PI AGRAWAL, NISHANT, LINGEN, MARK W. · 2020 to 2024
$1.9M
NCI NIH HHS P30 CA016672NIDCR NIH HHS R01 DE027809NIDCR NIH HHS R01 DE028674
6 · The paper itself

Abstract

Adenoid cystic carcinoma (ACC) is an aggressive salivary gland malignancy with limited treatment options for recurrent or metastatic disease. Due to chemotherapy resistance and lack of targeted therapeutic approaches, current treatment options for the localized disease are limited to surgery and radiation, which fails to prevent locoregional recurrences and distant metastases in over 50% of patients. Approximately 20% of patients with ACC carry NOTCH-activating mutations that are associated with a distinct phenotype, aggressive disease, and poor prognosis. Given the role of NOTCH signaling in regulating tumor cell behavior, NOTCH inhibitors represent an attractive potential therapeutic strategy for this subset of ACC. AL101 (osugacestat) is a potent γ-secretase inhibitor that prevents activation of all four NOTCH receptors. While this investigational new drug has demonstrated antineoplastic activity in several preclinical cancer models and in patients with advanced solid malignancies, we are the first to study the therapeutic benefit of AL101 in ACC. Here, we describe the antitumor activity of AL101 using ACC cell lines, organoids, and patient-derived xenograft models. Specifically, we find that AL101 has potent antitumor effects in in vitro and in vivo models of ACC with activating NOTCH1 mutations and constitutively upregulated NOTCH signaling pathway, providing a strong rationale for evaluation of AL101 in clinical trials for patients with NOTCH-driven relapsed/refractory ACC.

Indexed as

Carcinoma, Adenoid CysticSalivary Gland NeoplasmsAmyloid Precursor Protein SecretasesEnzyme InhibitorsHumansNeoplasm Recurrence, LocalReceptors, NotchSignal TransductionAmyloid Precursor Protein SecretasesEnzyme InhibitorsReceptors, Notch

Identifiers

PMID35931701
PMCPMC9355983
OpenAlexW4289889091

What OpenQuestion holds

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Registered trials

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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.