ArticleCell systems2020
Torin2 Exploits Replication and Checkpoint Vulnerabilities to Cause Death of PI3K-Activated Triple-Negative Breast Cancer Cells.
Article in Cell systems, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic.Frontiers in oncology · 2022Pooled it
- Development and validation of hierarchical signature for precision individualized therapy based on the landscape associated with necroptosis in clear cell renal cell carcinoma.Frontiers in pharmacology · 2025Article
- Integrative modeling uncovers p21-driven drug resistance and prioritizes therapies for PIK3CA-mutant breast cancer.NPJ precision oncology · 2024Article
- Paired evaluation of machine-learning models characterizes effects of confounders and outliers.Patterns (New York, N.Y.) · 2023Article
- Multiplexed and reproducible high content screening of live and fixed cells using Dye Drop.Nature communications · 2022Article
- Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies.Journal of hematology & oncology · 2022Review
- Article
- Targeting the mTOR pathway using novel ATP‑competitive inhibitors, Torin1, Torin2 and XL388, in the treatment of glioblastoma.International journal of oncology · 2021Article
- Preclinical Studies on the Effect of Rucaparib in Ovarian Cancer: Impact of BRCA2 Status.Cells · 2021Article
- Review
- Methylation of NRN1 is a novel synthetic lethal marker of PI3K-Akt-mTOR and ATR inhibitors in esophageal cancer.Cancer science · 2021Article
- Targeting the PI3K/mTOR Pathway Augments CHK1 Inhibitor-Induced Replication Stress and Antitumor Activity in High-Grade Serous Ovarian Cancer.Cancer research · 2020Article
- Parallel global profiling of plant TOR dynamics reveals a conserved role for LARP1 in translation.eLife · 2020Article
- Rae1 drives NKG2D binding-dependent tumor development in mice by activating mTOR and STAT3 pathways in tumor cells.Cancer science · 2020Article
- Targeting the PI3K pathway and DNA damage response as a therapeutic strategy in ovarian cancer.Cancer treatment reviews · 2020Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Frequent mutation of PI3K/AKT/mTOR signaling pathway genes in human cancers has stimulated large investments in targeted drugs but clinical successes are rare. As a result, many cancers with high PI3K pathway activity, such as triple-negative breast cancer (TNBC), are treated primarily with chemotherapy. By systematically analyzing responses of TNBC cells to a diverse collection of PI3K pathway inhibitors, we find that one drug, Torin2, is unusually effective because it inhibits both mTOR and other PI3K-like kinases (PIKKs). In contrast to mTOR-selective inhibitors, Torin2 exploits dependencies on several kinases for S-phase progression and cell-cycle checkpoints, thereby causing accumulation of single-stranded DNA and death by replication catastrophe or mitotic failure. Thus, Torin2 and its chemical analogs represent a mechanistically distinct class of PI3K pathway inhibitors that are uniquely cytotoxic to TNBC cells. This insight could be translated therapeutically by further developing Torin2 analogs or combinations of existing mTOR and PIKK inhibitors.
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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.