Evidence map›Paper›PMID 41667501›Full record

ArticleNature communications2026

Targeting NHEJ activates STING signaling through MYC degradation to boost antitumor immunity in SCLC.

Subhamoy Chakraborty, Andrew Elliott, Utsav Sen, Charles Coleman, Vrinda Jethalia, Kedwin Ventura, Chih-Wei Fan, Ramja Sritharan, Avisek Banerjee, Yazhini Mahendravarman and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026
    Review
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

17 authors.

Subhamoy ChakrabortyDivision of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.
Andrew ElliottDepartment of Clinical and Translational Research, Caris Life Sciences Inc., Tempe, Arizona, USA.ORCID 0000-0001-8494-8031
Utsav SenDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Charles ColemanTisch Cancer Institute, Mount Sinai, New York, NY, USA.
Vrinda JethaliaTisch Cancer Institute, Mount Sinai, New York, NY, USA.
Kedwin VenturaDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Chih-Wei FanTisch Cancer Institute, Mount Sinai, New York, NY, USA.
Ramja SritharanDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Avisek BanerjeeDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Yazhini MahendravarmanDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Ari VanderwaldeDepartment of Clinical and Translational Research, Caris Life Sciences Inc., Tempe, Arizona, USA.ORCID 0000-0002-6842-2563
Balazs HalmosMontefiore Medical Center, Albert Einstein College of Medicine, New York, NY, USA.ORCID 0000-0001-7548-8360
Elisa de StanchinaAntitumor Assessment Core, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Hirokazu TaniguchiClinical Oncology Center, Nagasaki University Hospital, Nagasaki, Japan.
Deniz DemirciogluDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.ORCID 0000-0001-7857-0407
Dan HassonDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Triparna SenDivision of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA. triparna.sen@osumc.edu.ORCID 0000-0003-4673-7481

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Targeting replication stress signaling to overcome immune evasion in small cell lung cancerR01CA258784 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI SEN, TRIPARNA · 2021 to 2025
$2.4M
NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA258784Tisch Cancer Institute at the Icahn School of Medicine at Mount SinaiU.S. Department of Defense (United States Department of Defense) DOD IITRA
6 · The paper itself

Abstract

Small-cell lung cancer (SCLC) is the most lethal type of lung cancer. Paradoxically, this tumor displays a high mutation burden; however, a modest response to immunotherapy. Improving Immunotherapy response in SCLC patients remains an unmet need. Here, we report that across 24 tumor types, including over 179,000 real-world patient tumors, SCLC has the highest expression of nonhomologous end joining (NHEJ) DNA repair regulator PRKDC (DNAPKcs). High PRKDC expression predicts poor response to immunotherapy in SCLC. DNAPKcs depletion causes activation of cGAS/STING pathway due to cytoplasmic accumulation of double-stranded DNA, inducing immunogenicity and enhancing sensitivity of SCLC models to immunotherapy. Analyses in SCLC cell lines and mouse models shows that depletion of DNAPKcs leads to proteasomal degradation of MYC via GSK3β pathway. We show that DNAPKcs upregulation contributes to immunotherapy resistance and DNAPKcs inhibition represents a promising therapeutic strategy to induce antitumor immunity and potentiate immunotherapy efficacy in immunologically suppressed SCLC.

Indexed as

DNA End-Joining RepairLung NeoplasmsMembrane ProteinsProto-Oncogene Proteins c-mycSmall Cell Lung CarcinomaAnimalsCell Line, TumorcGAS-STING Signaling PathwayCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNA-Activated Protein KinaseFemaleGene Expression Regulation, NeoplasticGlycogen Synthase Kinase 3 betaHumansImmunotherapyMicecGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNA-Activated Protein KinaseGlycogen Synthase Kinase 3 betaMembrane ProteinsMYC protein, humanNucleotidyltransferasesPRKDC protein, humanProto-Oncogene Proteins c-mycSTING1 protein, humanSTING Protein

Identifiers

PMID41667501
PMCPMC13003128

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.