ArticleCancer cell2022
MPS1 inhibition primes immunogenicity of KRAS-LKB1 mutant lung cancer.
Open access · greenAbstract read
In one paragraph
Article in Cancer cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
7.2field-weighted citation impact, top 2% of its field
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
74 citing papers in PubMed, 94 citations in OpenAlex.
- Cancers modulate processing and presentation of p53 neoantigens to evade T cell detection.Immunity · 2026Article
- Molecular insights and therapeutic implications for the tumor suppressor role of LKB1 in non-small cell lung cancer.Cancer letters · 2026Review
- Review
- KRAS signaling networks, mutational heterogeneity, and emerging therapeutic strategies for cancer treatment.Biomarker research · 2026Review
- TTK Overexpression as a Prognostic Indicator and Immune Modulator in Kidney Renal Clear Cell Carcinoma.Molecular carcinogenesis · 2026Article
- From energy metabolic homeostasis to immune remodeling: the role and therapeutic potential of STING signaling in the tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- cGAMP suppresses FTO expression to promote mCellular and molecular life sciences : CMLS · 2026Article
- CTMP-REV7 axis modulates MHC-I antigen presentation via CDK1-AKT crosstalk in MSI-L/MSS colorectal cancer.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- PTPN2 inhibition unleashes response to STING agonism in head and neck squamous cell cancer.Nature communications · 2026Article
- Methyltransferase SETD7 as a Regulator of STING-Dependent Cytokine Response in Lung Cancer Cells.International journal of molecular sciences · 2026Article
- Targeting CRTC2 reversesProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Vascular STING activation facilitates NK cell anti-tumor immunity in small cell lung cancer.Cancer cell · 2026Article
- Cancer and aging: complex associations and therapeutic targets.Molecular biomedicine · 2026Review
- Micronuclei: origins, assays, mechanisms, diseases and treatments.Signal transduction and targeted therapy · 2026Review
- Mitotic Machinery Dysregulation in Lung Cancer: Biological Roles, Therapeutic Targeting, and Combination Strategies.Pharmaceutics · 2026Review
- Opportunities and challenges of targeting cGAS-STING in cancer.Nature reviews. Cancer · 2026Review
- Review
- RRM1 inhibition sensitizes lung adenocarcinoma to decitabine treatment.Cell death & disease · 2026Article
- Loss of MicroRNA-29b promotes DNMT3b-mediated STING downregulation to attenuate radiotherapy-induced antitumor immunity in KRAS-mutated colorectal cancer.NPJ precision oncology · 2026Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
28 authors at 6 institutions in 2 countries.
Shunsuke KitajimaDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA; Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, Japan. Electronic address: shunsuke.kitajima@jfcr.or.jp.
Tetsuo TaniDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA.
Benjamin F SpringerDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA; Experimental Therapeutics Core, Dana-Farber Cancer Institute, Boston, MA, USA; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
Marco CampisiDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA.
Tatsuya OsakiDepartment of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.
Koji HarataniDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA.
Minyue ChenDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA.
Erik H KnelsonDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA.
Navin R MahadevanDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA; Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Jessica RitterBreast Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.
Ryohei YoshidaDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA.
Jens KöhlerDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA.
Atsuko OginoDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA.
Ryu-Suke NozawaDepartment of Experimental Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
Shriram K SundararamanDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA; Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Tran C ThaiDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA.
Mizuki HommeDepartment of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, Japan.
Brandon PielDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA.
Sophie KivlehanDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
Bonje N ObuaDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
Connor PurcellDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA; Division of Biology and Medicine, Brown University, Providence, RI, USA.
Mamiko YajimaDepartment of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.
Thanh U BarbieBreast Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA; Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
Patrick H LizotteDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
Pasi A JänneDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA.
Cloud P PaweletzDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
Prafulla C GokhaleDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA; Experimental Therapeutics Core, Dana-Farber Cancer Institute, Boston, MA, USA; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
David A BarbieDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA LC4115, USA. Electronic address: david_barbie@dfci.harvard.edu.
Dana-Farber Cancer Institute · USDana-Farber Brigham Cancer Center · USJapanese Foundation For Cancer Research · JPBeth Israel Deaconess Medical Center · USBrown University · USTokyo Institute of Technology · JP
Funding
VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI JENNIFER W MACK · 1985 to 2026
$330.6MTargeting the cytokine circuitry of KRAS-driven lung cancerR01CA190394 · NCI · DANA-FARBER CANCER INST · PI David A Barbie · 2015 to 2026
$4.5MLocalized mRNA translation on the spindle -an essential mechanism for embryonic cell regulationR01GM126043 · NIGMS · BROWN UNIVERSITY · PI YAJIMA, MAMIKO · 2018 to 2022
$2.0MTargeting the immunologic vulnerabilities of small cell lung carcinomaK08CA270077 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Navin Mahadevan · 2022 to 2026
$1.0MFunctional contribution of Metabolism in embryonic developmentR21HD109132 · NICHD · BROWN UNIVERSITY · PI YAJIMA, MAMIKO · 2022 to 2023
$439kNCI NIH HHS K08 CA270077NCI NIH HHS P30 CA006516NCI NIH HHS R01 CA190394NIGMS NIH HHS R01 GM126043
Abstract
KRAS-LKB1 (KL) mutant lung cancers silence STING owing to intrinsic mitochondrial dysfunction, resulting in T cell exclusion and resistance to programmed cell death (ligand) 1 (PD-[L]1) blockade. Here we discover that KL cells also minimize intracellular accumulation of 2'3'-cyclic GMP-AMP (2'3'-cGAMP) to further avoid downstream STING and STAT1 activation. An unbiased screen to co-opt this vulnerability reveals that transient MPS1 inhibition (MPS1i) potently re-engages this pathway in KL cells via micronuclei generation. This effect is markedly amplified by epigenetic de-repression of STING and only requires pulse MPS1i treatment, creating a therapeutic window compared with non-dividing cells. A single course of decitabine treatment followed by pulse MPS1i therapy restores T cell infiltration in vivo, enhances anti-PD-1 efficacy, and results in a durable response without evidence of significant toxicity.
Indexed as
Lung NeoplasmsProto-Oncogene Proteins p21(ras)DecitabineGenes, rasHumansLigandsDecitabineKRAS protein, humanLigandsProto-Oncogene Proteins p21(ras)2’3’-cGAMPcGASDNMT1EZH2KRAS-LKB1 mutant lung adenocarcinomamonopolar spindle kinase 1STING
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
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 OpenQuestion graph.