Evidence map›Paper›PMID 42559234›Full record

ArticleTheranostics2026

CTPS1 is an unexplored vulnerability in breast and ovarian cancer.

Xiyin Wang, Michael J Emch, Lauren A Voll, Rebecca Epp, Esther P B Rodman, Noa J Odell, Hannah M Smith, Nicole A Pearson, Xiaonan Hou, Ya Li and 8 more

Abstract read
In one paragraph

Article in Theranostics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

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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.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

18 authors.

Xiyin WangGraduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, USA.
Michael J EmchDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Lauren A VollDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Rebecca EppDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Esther P B RodmanDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Noa J OdellGraduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, USA.
Hannah M SmithGraduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, USA.
Nicole A PearsonDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Xiaonan HouDepartment of Oncology, Mayo Clinic, Rochester, MN, USA.
Ya LiGraduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, USA.
Melissa C LarsonDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Ann L ObergDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Taro HitosugiDepartment of Oncology, Mayo Clinic, Rochester, MN, USA.
Matthew P GoetzDepartment of Oncology, Mayo Clinic, Rochester, MN, USA.
Scott H KaufmannDepartment of Oncology, Mayo Clinic, Rochester, MN, USA.
S John WerohaDepartment of Oncology, Mayo Clinic, Rochester, MN, USA.
Philip A BeerStep Pharma, Saint-Genis-Pouilly, France.
John R HawseDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.

Funding

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
Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI SCOTT H KAUFMANN · 2009 to 2026
$37.0M
ERβ repurposes EZH2 to suppress oncogenic NFκB signaling in TNBCR01CA249116 · NCI · MAYO CLINIC ROCHESTER · PI HAWSE, JOHN R. · 2021 to 2025
$2.4M
NCI NIH HHS P50 CA116201NCI NIH HHS P50 CA136393NCI NIH HHS R01 CA249116
6 · The paper itself

Abstract

Triple negative breast cancer (TNBC) and ovarian cancer share many molecular features and are primarily treated with surgical resection and aggressive chemotherapy regimens. Unfortunately, survival rates for patients with advanced metastatic disease are poor, highlighting the need for innovative therapeutic approaches. Methods: Using the DepMap database, we first sought to identify genes that were highly expressed and more essential for proliferation/viability in TNBC cells relative to other breast cancer subtypes. Candidate genes were validated using gene-specific siRNAs in a panel of TNBC and estrogen receptor positive breast cancer cells. CTPS1 expression, and its functional significance, was further evaluated in ovarian cancer models, including chemotherapy- and PARP inhibitor-resistant cell lines. Pharmacologic inhibition was assessed using STP938, a first-in-class selective CTPS1 inhibitor, in TNBC and ovarian cancer cells as well as in Results: Six genes (CTPS1, HUS1, PRKRA, RAD1, RAD9A, and RHOA) were identified as potential TNBC selective dependencies. Among these, CTPS1 was prioritized for further study given that it was highly expressed, further upregulated in chemotherapy- and PARP inhibitor-resistant cell lines, and resulted in the greatest anti-neoplastic effects when depleted. Knockdown of CTPS1 confirmed its selective essentiality and resulted in rapid and durable S-phase cell cycle arrest. Pharmacologic inhibition of CTPS1 with STP938 led to robust anti-neoplastic effects at nM concentrations across both chemotherapy-sensitive and -resistant TNBC and ovarian cancer cell lines. Significant anti-neoplastic activity was observed in 6 independent Conclusion: These findings identify CTPS1 as a critical dependency in TNBC and ovarian cancer. Selective pharmacologic inhibition of CTPS1 using STP938 is a potent inhibitor of tumor cell proliferation/viability and has anti-cancer activity in patient derived

Indexed as

Ovarian NeoplasmsTriple Negative Breast NeoplasmsAnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationFemaleHumansMiceXenograft Model Antitumor AssaysAntineoplastic AgentsCTPS1drug resistanceovarian cancertargeted therapytriple negative breast cancer

Identifiers

PMID42559234
PMCPMC13440435

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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.