Evidence map›Paper›PMID 36077757›Full record

ArticleCancers2022

Identification of Src Family Kinases as Potential Therapeutic Targets for Chemotherapy-Resistant Triple Negative Breast Cancer.

Ishwar N Kohale, Jia Yu, Yongxian Zhuang, Xiaoyang Fan, Raven J Reddy, Jason Sinnwell, Krishna R Kalari, Judy C Boughey, Jodi M Carter, Matthew P Goetz and 2 more

Abstract read
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
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

12 citing papers in PubMed.

  1. Article
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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.

Ishwar N KohaleDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Jia YuDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Yongxian ZhuangDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Xiaoyang FanDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Raven J ReddyDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Jason SinnwellDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA.
Krishna R KalariDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA.
Judy C BougheyDepartment of Surgery, Mayo Clinic, Rochester, MN 55905, USA.
Jodi M CarterDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Matthew P GoetzDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Liewei WangDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Forest M WhiteDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0002-1545-1651

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
The Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI PETER C LUCAS · 2005 to 2026
$49.9M
The MIT Superfund Research Program: A Systems Approach for the Protection of Human Health from Hazardous ChemicalsP42ES027707 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Bevin P. Engelward · 2017 to 2026
$22.2M
Trans Network ProjectU54CA210180 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SARKARIA, JANN N., WHITE, FOREST M · 2016 to 2020
$10.2M
Identification of adaptive response mechanisms in breast cancer by information theory and proteomicsU01CA238720 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KRAVCHENKO-BALASHA, NATALY, WHITE, FOREST M · 2019 to 2023
$2.0M
Mayo Clinic Breast Cancer Specialized Program of Research Excellence Grant P50CA 116201MIT Center for Precision Cancer Medicine NANCI NIH HHS P30 CA014051NCI NIH HHS P30 CA015083NCI NIH HHS P50 CA116201NCI NIH HHS U01 CA238720NCI NIH HHS U54 CA210180NIEHS NIH HHS P42 ES027707NIH HHS P30 CA14051NIH HHS P42 ES027707NIH HHS U01 CA238720NIH HHS U54 CA210180
6 · The paper itself

Abstract

Neoadjuvant chemotherapy (NAC) remains the cornerstone of the treatment for triple negative breast cancer (TNBC), with the goal of complete eradication of disease. However, for patients with residual disease after NAC, recurrence and mortality rates are high and the identification of novel therapeutic targets is urgently needed. We quantified tyrosine phosphorylation (pTyr)-mediated signaling networks in chemotherapy sensitive (CS) and resistant (CR) TNBC patient-derived xenografts (PDX), to gain novel therapeutic insights. The antitumor activity of SFK inhibition was examined in vivo. Treated tumors were further subjected to phosphoproteomic and RNAseq analysis, to identify the mechanism of actions of the drug. We identified Src Family Kinases (SFKs) as potential therapeutic targets in CR TNBC PDXs. Treatment with dasatinib, an FDA approved SFK inhibitor, led to inhibition of tumor growth in vivo. Further analysis of post-treatment PDXs revealed multiple mechanisms of actions of the drug, confirming the multi-target inhibition of dasatinib. Analysis of pTyr in tumor specimens suggested a low prevalence of SFK-driven tumors, which may provide insight into prior clinical trial results demonstrating a lack of dasatinib antitumor activity in unselected breast cancer patients. Taken together, these results underscore the importance of pTyr characterization of tumors, in identifying new targets, as well as stratifying patients based on their activated signaling networks for therapeutic options. Our data provide a strong rationale for studying SFK inhibitors in biomarker-selected SFK-driven TNBC.

Indexed as

chemotherapy resistancephosphoproteomicssrc family kinasestriple negative breast cancer

Identifiers

PMID36077757
PMCPMC9454481

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.