Evidence map›Paper›PMID 35568265›Full record

ArticleCancer letters2022

The antidepressant imipramine inhibits breast cancer growth by targeting estrogen receptor signaling and DNA repair events.

Santosh Timilsina, Subapriya Rajamanickam, Arhan Rao, Panneerdoss Subbarayalu, Saif Nirzhor, Nourhan Abdelfattah, Suryavathi Viswanadhapalli, Yidong Chen, Ismail Jatoi, Andrew Brenner and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Cancer letters, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.1field-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

17 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
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  7. Drug repurposing in oncology: a path beyond the bottleneck.Medical oncology (Northwood, London, England) · 2025
    Review
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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

13 authors at 3 institutions in 1 country.

Santosh TimilsinaDepartment of Cell Systems and Anatomy, UT Health, San Antonio, USA; Greehey Children's Cancer Research Institute, USA.
Subapriya RajamanickamGreehey Children's Cancer Research Institute, USA; Department of Molecular Medicine, UT Health, San Antonio, USA.
Arhan RaoHealth Careers High School, San Antonio, TX, USA.
Panneerdoss SubbarayaluDepartment of Cell Systems and Anatomy, UT Health, San Antonio, USA; Greehey Children's Cancer Research Institute, USA.
Saif NirzhorDepartment of Cell Systems and Anatomy, UT Health, San Antonio, USA; Greehey Children's Cancer Research Institute, USA.
Nourhan AbdelfattahHouston Methodist, Houston, TX, USA.
Suryavathi ViswanadhapalliDepartment of Obstetrics and Gynecology, UT Health, San Antonio, USA.
Yidong ChenGreehey Children's Cancer Research Institute, USA; Department of Epidemiology and Statistics, UT Health, San Antonio, USA.
Ismail JatoiDepartment of Surgery, UT Health, San Antonio, USA.
Andrew BrennerDepartment of Medicine, UT Health, San Antonio, USA.
Manjeet K RaoDepartment of Cell Systems and Anatomy, UT Health, San Antonio, USA; Greehey Children's Cancer Research Institute, USA. Electronic address: raom@uthscsa.edu.
Ratna VadlamudiDepartment of Obstetrics and Gynecology, UT Health, San Antonio, USA. Electronic address: vadlamudi@uthscsa.edu.
Virginia KaklamaniDepartment of Medicine, UT Health, San Antonio, USA. Electronic address: Kaklamani@uthscsa.edu.
The University of Texas Health Science Center at Houston · USThe University of Texas Health Science Center at San Antonio · USHouston Methodist · US

Funding

TISSUE CULTURE---COREP30CA054174 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Lei Zheng · 1991 to 2026
$59.1M
Institute for Integration of Medicine & Science: A Partnership to Improve HealthUL1TR001120 · NCATS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI CLARK, ROBERT A, HARGREAVES, KENNETH M · 2013 to 2017
$16.5M
Cancer Biology Training ProgramT32CA148724 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Pei Wang, Feng-Chun Yang · 2011 to 2026
$3.3M
FoXM1 inhibition: a novel therapeutic avenue to treat breast cancersR01CA239227 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI RAO, MANJEET KUMAR, VADLAMUDI, RATNA K · 2020 to 2024
$2.1M
miRNAs:Safe and effective therapeutic adjuvants for treating drug resistant TNBCR01CA179120 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI RAO, MANJEET KUMAR, VADLAMUDI, RATNA K · 2015 to 2019
$1.7M
NCATS NIH HHS UL1 TR001120NCI NIH HHS P30 CA054174NCI NIH HHS R01 CA179120NCI NIH HHS R01 CA239227NCI NIH HHS T32 CA148724
6 · The paper itself

Abstract

Aberrant activities of various cell cycle and DNA repair proteins promote cancer growth and progression and render them resistant to therapies. Here, we demonstrate that the anti-depressant imipramine blocks growth of triple-negative (TNBC) and estrogen receptor-positive (ER+) breast cancers by inducing cell cycle arrest and by blocking heightened homologous recombination (HR) and non-homologous end joining-mediated (NHEJ) DNA repair activities. Our results reveal that imipramine inhibits the expression of several cell cycle- and DNA repair-associated proteins including E2F1, CDK1, Cyclin D1, and RAD51. In addition, we show that imipramine inhibits the growth of ER + breast cancers by inhibiting the estrogen receptor- α (ER-α) signaling. Our studies in preclinical mouse models and ex vivo explants from breast cancer patients show that imipramine sensitizes TNBC to the PARP inhibitor olaparib and endocrine resistant ER + breast cancer to anti-estrogens. Our studies suggest that repurposing imipramine could enhance routine care for breast cancer patients. Based on these results, we designed an ongoing clinical trial, where we are testing the efficacy of imipramine for treating patients with triple-negative and estrogen receptor-positive breast cancer. Since aberrant DNA repair activity is used by many cancers to survive and become resistant to therapy, imipramine could be used alone and/or with currently used drugs for treating many aggressive cancers.

Indexed as

Breast NeoplasmsTriple Negative Breast NeoplasmsAnimalsAntidepressive AgentsCell Line, TumorCell ProliferationDNA RepairFemaleHumansImipramineMiceReceptors, EstrogenAntidepressive AgentsImipramineReceptors, EstrogenBreast cancerDNA damageDNA repairDrug repurposingEstrogen receptorImipramine

Identifiers

PMID35568265
PMCPMC10313451
OpenAlexW4280602031

What Socratic holds

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LicenceCC BY-NC
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 Socratic graph.