ArticleOncogene2019
A novel proteotoxic combination therapy for EGFR+ and HER2+ cancers.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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.
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.
Who cites it
8 citing papers in PubMed, 17 citations in OpenAlex.
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Beta-cyclodextrin formulation of a disulfide-bond disrupting agent for improved systemic exposure.RSC medicinal chemistry · 2025Article
- Non-Canonical, Strongly Selective Protein Disulfide Isomerases as Anticancer Therapeutic Targets.Biomolecules · 2025Review
- DR5 Disulfide Bonding Functions as a Sensor and Effector of Protein Folding Stress.Molecular cancer research : MCR · 2025Article
- Anticancer Agents Derived from Cyclic Thiosulfonates: Structure-Reactivity and Structure-Activity Relationships.ChemMedChem · 2022Article
- Upregulated MUC2 Is an Unfavorable Prognostic Indicator for Rectal Cancer Patients Undergoing Preoperative CCRT.Journal of clinical medicine · 2021Article
- Repurposing Tranexamic Acid as an Anticancer Agent.Frontiers in pharmacology · 2021Article
- Disulfide bond-disrupting agents activate the tumor necrosis family-related apoptosis-inducing ligand/death receptor 5 pathway.Cell death discovery · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While HER2 and EGFR are overexpressed in breast cancers and multiple other types of tumors, the use of EGFR and/or HER2 inhibitors have failed to cure many cancer patients, largely because cancers acquire resistance to HER2/EGFR-specific drugs. Cancers that overexpress the HER-family proteins EGFR, HER2, and HER3 are uniquely sensitive to agents that disrupt HER2 and EGFR protein folding. We previously showed that disruption of disulfide bond formation by Disulfide Disrupting Agents (DDAs) kills HER2/EGFR overexpressing cells through multiple mechanisms. Herein, we show that interference with proline isomerization in HER2/EGFR overexpressing cells also induces cancer cell death. The peptidyl-prolyl isomerase inhibitor Cyclosporine A (CsA) selectively kills EGFR+ or HER2+ breast cancer cells in vitro by activating caspase-dependent apoptotic pathways. Further, CsA synergizes with the DDA tcyDTDO to kill HER2/EGFR overexpressing cells in vitro and the two agents cooperate to kill HER2+ tumors in vivo. There is a critical need for novel strategies to target HER2+ and EGFR+ cancers that are resistant to currently available mechanism-based agents. Drugs that target HER2/EGFR protein folding, including DDAs and CsA, have the potential to kill cancers that overexpress EGFR or HER2 through the induction of proteostatic synthetic lethality.
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What OpenQuestion holds
Registered trials
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.