Cited by 186Sarcoma Diagnosis and TreatmentPARP inhibition in cancer therapyChromatin Remodeling and Cancer

The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.

EWS/FLI Confers Tumor Cell Synthetic Lethality to CDK12 Inhibition in Ewing Sarcoma

Open access

Iniguez, Amanda Balboni, Stolte, Björn, Wang, Emily Jue, Conway, Amy Saur, Alexe, Gabriela, Dharia, Neekesh V., Kwiatkowski, Nicholas, Zhang, Tinghu, Abraham, Brian J., Mora, Jaume, Kalev, Peter, Leggett, Alan, Chowdhury, Dipanjan, Benes, Cyril H., Young, Richard A., Gray, Nathanael S., Stegmaier, Kimberly·2018·Cancer Cell

DOI 10.1016/j.ccell.2017.12.009PMC PMC5846483

Open this paper in CoChat — free account Open PDF

Abstract

Many cancer types are driven by oncogenic transcription factors that have been difficult to drug. Transcriptional inhibitors, however, may offer inroads into targeting these cancers. Through chemical genomics screening, we identified that Ewing sarcoma is a disease with preferential sensitivity to THZ1, a covalent small-molecule CDK7/12/13 inhibitor. The selective CDK12/13 inhibitor, THZ531, impairs DNA damage repair in an EWS/FLI-dependent manner, supporting a synthetic lethal relationship between response to THZ1/THZ531 and EWS/FLI expression. The combination of these molecules with PARP inhibitors showed striking synergy in cell viability and DNA damage assays in vitro and in multiple models of Ewing sarcoma, including a PDX, in vivo without hematopoietic toxicity.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1016/j.ccell.2017.12.009

Cites

43 of 43 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197
Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors
Chou, T.-C., & Talalay, P. (1984) · Advances in Enzyme Regulation · doi:10.1016/0065-2571(84)90007-4 · Cited by 7,178
Mutational heterogeneity in cancer and the search for new cancer-associated genes
Lawrence, M. S., Stojanov, P., Polak, P., Kryukov, G. V., Cibulskis, K., Sivachenko, A., Carter, S. L., Stewart, C., Mermel, C. H., Roberts, S. A., et al. (2013) · Nature · doi:10.1038/nature12213 · Cited by 5,461
Self-citation
Improved vectors and genome-wide libraries for CRISPR screening
Sanjana, N. E., Shalem, O., & Zhang, F. (2014) · Nature Methods · doi:10.1038/nmeth.3047 · Cited by 5,239
Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies
Chou, T.-C. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.10 · Cited by 5,163
Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells
Yang, W., Soares, J., Greninger, P., Edelman, E. J., Lightfoot, H., Forbes, S., Bindal, N., Beare, D., Smith, J. A., Thompson, I. R., et al. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1111 · Cited by 4,051
Self-citation
Systematic identification of genomic markers of drug sensitivity in cancer cells
Garnett, M. J., Edelman, E. J., Heidorn, S. J., Greenman, C. D., Dastur, A., Lau, K. W., Greninger, P., Thompson, I. R., Luo, X., Soares, J., et al. (2012) · Nature · doi:10.1038/nature11005 · Cited by 2,456
Self-citation
Computational correction of copy number effect improves specificity of CRISPR-Cas9 essentiality screens in cancer cells
Meyers, R. M., Bryan, J. G., McFarland, J. M., Weir, B. A., Sizemore, A. E., Xu, H., Dharia, N. V., Montgomery, P. G., Cowley, G. S., Pantel, S., et al. (2017) · Nature Genetics · doi:10.1038/ng.3984 · Cited by 1,952
Self-citation
Lentivirus-delivered stable gene silencing by RNAi in primary cells.
Stewart, S. A., Dykxhoorn, D. M., Palliser, D., Mizuno, H., Yu, E. Y., An, D., Sabatini, D., Chen, I. S. Y., Hahn, W., Sharp, P., et al. (2003) · RNA: A publication of the RNA Society · doi:10.1261/rna.2192803 · Cited by 1,619
The search for synergy: a critical review from a response surface perspective.
Greco, W. R., Bravo, G., & Parsons, J. C. (1995) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06847-4 · Cited by 1,445

Flagged first, then by citations

Show all 43 references

Sorted by citations

Items 101–186 of 186

Exploiting targeted degradation of cyclins and cyclin-dependent kinases for cancer therapeutics: a review
Zheng, S., Chen, Y., Zhu, Z., Li, N., He, C., Koeffler, H. P., Han, X., Wei, Q., & Xu, L. (2025) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b2500021 · Cited by 9
Targeting Super-Enhancer–Driven Transcriptional Dependencies Suppresses Aberrant Hedgehog Pathway Activation and Overcomes Smoothened Inhibitor Resistance
Sui, Y., Wang, T., Mei, Y., Zhu, Y., Jiang, W., Shen, J., Yan, S., Lu, W., Zhao, K., Mo, J., et al. (2024) · Cancer Research · doi:10.1158/0008-5472.can-23-3306 · Cited by 9
A review on kinases phosphorylating the carboxyl-terminal domain of RNA polymerase II—Biological functions and inhibitors
Zhang, J., Zhang, X., Huang, H., & Ding, Y. (2020) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2020.104318 · Cited by 9
Current Approaches for Personalized Therapy of Soft Tissue Sarcomas
Игоревич, К. К., Lesovaya, E. A., Fetisov, T. I., Bokhyan, B. Y., Belitsky, G. A., & Геннадиевна, Я. М. (2020) · Sarcoma · doi:10.1155/2020/6716742 · Cited by 8
Antitumoral activity of a CDK12 inhibitor in colorectal cancer through a liposomal formulation
Díaz‐Tejeiro, C., Arenas-Moreira, M., Sanvicente, A., Paniagua‐Herranz, L., Clemente-Casares, P., Bravo, I., Alonso‐Moreno, C., Nieto‐Jiménez, C., & Ocaña, A. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117165 · Cited by 7
Further Understanding of High-Grade Serous Ovarian Carcinogenesis: Potential Therapeutic Targets
Voutsadakis, I. A. (2020) · Cancer Management and Research · doi:10.2147/cmar.s249540 · Cited by 8
Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario
Cândido, M. F., Medeiros, M., Veronez, L. C., Bastos, D., Oliveira, K. L., Pezuk, J. A., Valera, E. T., & Brassesco, M. S. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020664 · Cited by 8
PARP inhibitor combinations with high-dose vitamin C in the treatment of Ewing sarcoma: two case reports and mechanistic overview
Adibi, A., Tokat, Ü. M., Özgü, E., Aydın, E., Demiray, İ., & Demiray, M. (2023) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359231213841 · Cited by 7
Targeted Combination of Poly(ADP-ribose) Polymerase Inhibitors and Immune Checkpoint Inhibitors Lacking Evidence of Benefit: Focus in Ovarian Cancer
Bailey, M. M., Morand, S. M., Royfman, R., Lin, L., Singh, A. P., Stanbery, L., Walter, A., Hamouda, D., & Nemunaitis, J. J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063173 · Cited by 7
Next-generation sequencing identifies potential novel therapeutic targets in Chinese HGSOC patients
Tao, J., Sun, D., Zhou, H., Zhu, J., Zhang, X., & Hou, H. (2022) · Pathology - Research and Practice · doi:10.1016/j.prp.2022.154074 · Cited by 6
CDK12 /13 dual inhibitors are potential therapeutics for acute myeloid leukemia
Savoy, L., Long, N., Lee, H., Chen, R., Allen, B., Lin, H., Tognon, C. E., Malhotra, S. V., Tyner, J. W., & Zhang, H. (2023) · British Journal of Haematology · doi:10.1111/bjh.18843 · Cited by 6
CSSLdb: Discovery of cancer-specific synthetic lethal interactions based on machine learning and statistic inference
Dou, Y., Ren, Y., Zhao, X., Jin, J., Xiong, S., Luo, L., Xu, X., Yang, X., Yu, J., Guo, L., et al. (2024) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2024.108066 · Cited by 6
Loss of heterozygosity impacts MHC expression on the immune microenvironment in CDK12-mutated prostate cancer
Lautert-Dutra, W., Melo, C. M., Chaves, L. P., Crozier, C., Saggioro, F. P., dos Reis, R. B., Bayani, J., Bonatto, S. L., & Squire, J. A. (2024) · Molecular Cytogenetics · doi:10.1186/s13039-024-00680-6 · Cited by 6
Repression of PRMT activities sensitize human homologous recombination-proficient ovarian and breast cancer cells to PARP inhibitor treatment
Zhang, Y., Xu, M., Yuan, J., Hu, Z., Jiang, J., Sun, Y., Huang, J. S., Wang, Y., Wang, B., Shen, J., et al. (2024) · eLife · doi:10.7554/elife.99225 · Cited by 8
Paediatric strategy forum for medicinal product development of cyclin-dependent kinase inhibitors in children and adolescents ACCELERATE in collaboration with the European Medicines Agency With participation of the Food and Drug Administration
Pearson, A. D. J., Chi, S. N., Laetscht, T. W., Marshall, L. V., Raetz, E. A., George, R. E., Chesler, L., Karres, D., Scobie, N., Knoderer, H. M., et al. (2025) · European Journal of Cancer · doi:10.1016/j.ejca.2025.115629 · Cited by 5
CDK10 suppresses nucleic acid sensors-mediated antitumor immunity
Xu, G., Guo, F., He, C., Wang, X., Xiang, B., Fan, L., Chen, B., Peng, J., Sun, Y., Shi, J., et al. (2026) · Nature Cancer · doi:10.1038/s43018-025-01100-3 · Cited by 5
Disruption of microhomology-mediated end joining in Ewing sarcoma
Asada, S., Zhu, G., Abeykoon, J. P., Tanaka, Y., Nguyen, H., Hirohashi, Y., Iyer, D., Ashton, N. W., Mukkavalli, S., Velazquez, M., et al. (2026) · Molecular Cell · doi:10.1016/j.molcel.2026.06.038 · Cited by 5
Targeting the transcription cycle and RNA processing in cancer treatment
Zhang, L., Zhang, Y., & Hu, X. (2021) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2021.04.001 · Cited by 5
Multi-omics investigation reveals functional specialization of transcriptional cyclin dependent kinases in cancer biology
Donovan, M. G., Galbraith, M. D., & Espinosa, J. M. (2022) · Scientific Reports · doi:10.1038/s41598-022-26860-1 · Cited by 5
Recurrent and Refractory Ewing Sarcoma Phase I/II Trials: Current Perspective From the Euro-Ewing Consortium
Ribelles, A. J., Felix, A., Benavent, N., Escrivá-Fernández, J., Brahmi, M., Gaspar, N., Gatz, S. A., Grünewald, T. G. P., Linder‐Stragliotto, C., Palmerini, E., et al. (2025) · JCO Precision Oncology · doi:10.1200/po-25-00377 · Cited by 4
AI-enabled cancer target prioritization with optimal profiles balancing novelty, confidence and commercial tractability
Long, X., Steurer, B., Wong, C. W., Kozlova, E., Naumov, V., Pun, F. W., Aliper, A., Ren, F., & Zhavoronkov, A. A. (2024) · Future Medicine AI · doi:10.2217/fmai-2023-0019 · Cited by 4
Comutation of PIK3CA and TP53 in Residual Disease After Preoperative Anti-HER2 Therapy in ERBB2 (HER2)-Amplified Early Breast Cancer
Holmes, F. A., Levin, M. K., Cao, Y., Balasubramanian, S., Ross, J. S., Krekow, L., McIntyre, K. J., Osborne, C. R. C., Espina, V. A., Liotta, L. A., et al. (2019) · JCO Precision Oncology · doi:10.1200/po.18.00292 · Cited by 4
Seclidemstat blocks the transcriptional function of multiple FET-fusion oncoproteinsPreprint
Rask, G. C., Taslim, C., Bayanjargal, A., Cannon, M. V., Selich‐Anderson, J., Crow, J. C., Duncan, A. D., & Theisen, E. R. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.19.594897 · Cited by 4
Seclidemstat (SP-2577) Induces Transcriptomic Reprogramming and Cytotoxicity in Multiple Fusion–Positive Sarcomas
Rask, G. C., Taslim, C., Bayanjargal, A., Dreher, R. D., Cannon, M. V., Selich‐Anderson, J., Crow, J. C., Duncan, A. D., & Theisen, E. R. (2025) · Cancer Research Communications · doi:10.1158/2767-9764.crc-24-0296 · Cited by 3
The role of CDK12 in tumor biology
Dzimková, M., Procházková, J., Klát, J., & Kohoutek, J. (2020) · Klinicka onkologie · doi:10.14735/amko2020260 · Cited by 3
Quest for discovering novel CDK12 inhibitor
Debnath, A., Singh, R. K., Mazumder, R., Mazumder, A., Srivastava, S., Chaudhary, H., Mangal, S., Sanchitra, J., Tyagi, P. K., Singh, S. K., et al. (2024) · Journal of Receptors and Signal Transduction · doi:10.1080/10799893.2024.2441185 · Cited by 3
Gene signatures of cyclin- kinases: a comparative study in naïve early and advanced stages of lung metastasis breast cancer among pre- and post- women
Qureshi, M. F. H., Shah, M., Lakhani, M., Abubaker, Z. J., Mohammad, D., Farhan, H., Zia, I., Tafveez, R., Khan, S. T., Ghani, R., et al. (2021) · Genes & Cancer · doi:10.18632/genesandcancer.209 · Cited by 3
The Puzzle of Genetic Stability and Chromosomal Copy Number Alterations for the Therapy of Ewing Sarcoma
Richter, G. H. S., Ranft, A., Kerkhoff, M., Jens, M., Kirchberg, I. E., & Dirksen, U. (2025) · Cancers · doi:10.3390/cancers17223719 · Cited by 2
CDK12 and CDK13 in oncology: from RNA regulation to therapeutic targeting
Dudkiewicz-Garbicz, J., & Wlodarski, P. K. (2026) · Cellular Oncology · doi:10.1007/s13402-025-01131-z · Cited by 3
Roles of CDK12/CDK13 and development of inhibitors and degraders
Li, Z. F., Ke, Y., Zhang, R., Zhang, R., & Zhang, L. (2026) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2026.119077 · Cited by 3
Antitumor Effects of β-Elemene Through Inducing Autophagy-Mediated Apoptosis in Ewing Sarcoma Family Tumor Cells
Zhang, T., Zhang, T., Gao, C., Jalal, S., Yuan, R., Teng, H., Li, C., & Huang, L. (2023) · DNA and Cell Biology · doi:10.1089/dna.2023.0084 · Cited by 2
Self-citation
Development of CDK12 as a Cancer Therapeutic Target and Related Inhibitors
Chen, B., & Liu, J. (2024) · Current Cancer Drug Targets · doi:10.2174/0115680096307629240611104728 · Cited by 2
Contemporary Approach to Therapy for Ewing Sarcoma
DuBois, S. G., & Dirksen, U. (2020) · Pediatric oncology · doi:10.1007/978-3-030-51160-9_9 · Cited by 2
Cooperative regulation of coupled oncoprotein translation and stability in triple-negative breast cancer by EGFR and CDK12Preprint
Ang, H. X., Sutiman, N., Deng, X. L., Bartelt, L. C., Chen, Q., Barrera, A., Lin, J., Sheng, J., McDowell, I. C., Reddy, T. E., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.03.433762 · Cited by 2
CDK12/13 inhibitor, CTX-439, suppresses tumor growth and potentiates BCL-2 family blockadePreprint
Yamakawa, H., Khatab, R., Mizutani, A., Ebara, S., Hirayama, T., Tanaka, S., Tarumoto, Y., Sugiyama, M., Sugino, S., Takano, M., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.20.706902 · Cited by 3
Targeting CDKs with Other Chemotherapeutic Drugs: A Combinatorial Approach
Mir, M. A., & Mir, U. Y. (2023) · Springer eBooks · doi:10.1007/978-981-19-8911-7_13 · Cited by 1
Breaking the script: transcriptional addiction as a driver of genome instability in cancer
Hidmi, O., Wei, P., & Aqeilan, R. I. (2025) · Trends in Genetics · doi:10.1016/j.tig.2025.10.007 · Cited by 1
Therapeutic targeting of CDK12: a medicinal chemistry perspective
Wang, F., Dai, H., Wan, K., & Wang, M. (2026) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2026.118552 · Cited by 1
Alternative polyadenylation in cancer: mechanisms, functions, and therapeutic potential
Huang, Y., Li, Z., Yu, F., & Wang, L. (2026) · Molecular Cancer · doi:10.1186/s12943-026-02760-0 · Cited by 1
Systemic Treatment of Ewing Sarcoma: Current Options and Future Perspectives
Moreno, J. D., Papageorgiou, G., Gazouli, I., & Kyriazoglou, A. I. (2021) · Forum of Clinical Oncology · doi:10.2478/fco-2021-0005 · Cited by 1
Sarcoma Pathology and Biology
Yohe, M. E., Khan, J. I., & Rudzinski, E. R. (2020) · Pediatric oncology · doi:10.1007/978-3-030-51160-9_2 · Cited by 1
New connections: Ewing’s sarcoma’s driver is its Achilles’ heel
Ferrarelli, L. K. (2018) · Science Signaling · doi:10.1126/scisignal.aat9379 · Cited by 1
Repression of PRMT activities sensitize homologous recombination-proficient ovarian and breast cancer cells to PARP inhibitor treatmentPreprint
Zhang, Y., Xu, M., Yuan, J., Hu, Z., Jiang, J., Huang, J. S., Wang, B., Shen, J., Long, M., Fan, Y., et al. (2024) · eLife · doi:10.7554/elife.99225.1 · Cited by 1
Molecular consequences of acute versus chronic CDK12 loss in prostate carcinoma nominates distinct therapeutic strategiesPreprint
Frank, S. B., Persse, T. W., Coleman, I., Bankhead, A., Li, D., Sarkar, N. D., Wilson, D., Rudoy, D., Vashisth, M., Galipeau, P., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.16.603734 · Cited by 3
Molecular consequences of acute versus chronic CDK12 loss in prostate carcinoma nominates distinct therapeutic strategiesPreprint
Frank, S. B., Persse, T. W., Coleman, I., Bankhead, A., Li, D., Sarkar, N. D., Wilson, D., Rudoy, D., Vashisth, M., Galipeau, P., et al. (2025) · eLife · doi:10.7554/elife.100081.2 · Cited by 1
Novel Drug Treatments for Ewing Sarcoma
Hayden, R., & Leggas, M. L. (2019) · Current Molecular Biology Reports · doi:10.1007/s40610-019-00125-9
Development of molecular inhibitor nanoformulations for cancer therapy
Baldwin, P. (2019) · Digital Repository Service (Northeastern University) · doi:10.17760/d20317945
Automated compound testing in zebrafish xenografts identifies combined MCL-1 and BCL-X L inhibition to be effective against Ewing sarcomaPreprint
Grissenberger, S., Sturtzel, C., Wenninger-Weinzierl, A., Scheuringer, E., Bierbaumer, L., Pascoal, S., Tötzl, M., Tomazou, E. M., Delattre, O., Surdez, D., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.06.17.448794
Regulated cell death and drug resistance in malignant bone tumors
Richter, G. H. S., Lissat, A., & Kontny, U. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821666-8.00055-4
Faculty Opinions recommendation of PRMT5 Regulates DNA Repair by Controlling the Alternative Splicing of Histone-Modifying Enzymes.
Ness, S. A. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733951266.793550638
Bone Tumours - A Comprehensive Review of Selected Topics
Amarasekera, H. (2022) · IntechOpen eBooks · doi:10.5772/intechopen.100923
Drug Targeting of Chromosomal Translocations in Fusion-Positive Sarcoma
Richter, G. H. S. (2022) · IntechOpen eBooks · doi:10.5772/intechopen.106671
Data from Dual Inhibition of CDK12/CDK13 Targets Both Tumor and Immune Cells in Ovarian Cancer
Cheng, L., Zhou, S., Zhou, S., Shi, K., Cheng, Y., Cai, M., Ye, K., Lin, L., Zhang, Z., Jia, C., et al. (2023) · doi:10.1158/0008-5472.c.6514152.v1
Data from Pharmaceutical Interference of the EWS-FLI1–driven Transcriptome By Cotargeting H3K27ac and RNA Polymerase Activity in Ewing Sarcoma
Heisey, D. A. R., Jacob, S., Lochmann, T. L., Kurupi, R., Ghotra, M. S., Calbert, M. L., Shende, M., Maves, Y. K., Koblinski, J. E., Dozmorov, M. G., et al. (2023) · doi:10.1158/1535-7163.c.6542887
Self-citation
Supplementary table 3 from Pharmaceutical Interference of the EWS-FLI1–driven Transcriptome By Cotargeting H3K27ac and RNA Polymerase Activity in Ewing Sarcoma
Heisey, D. A. R., Jacob, S., Lochmann, T. L., Kurupi, R., Ghotra, M. S., Calbert, M. L., Shende, M., Maves, Y. K., Koblinski, J. E., Dozmorov, M. G., et al. (2023) · doi:10.1158/1535-7163.22521043
Self-citation
Acute BRCAness Induction and AR Signaling Blockage through CDK12/7/9 Degradation Enhances PARP Inhibitor Sensitivity in Prostate CancerPreprint
Gui, F., Jiang, B., Jiang, J., He, Z., Tsujino, T., Takai, T., Arai, S., Pana, C., Köllermann, J. W., Bradshaw, G. A., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.09.602803
LRR1 Acts as an Oncogenic Driver: Synthetic Lethality with PARP Inhibition in Triple-Negative Breast CancerPreprint
Wang, L., Chen, X., Chen, L., & Li, P. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4971486
Pansarcoma Analysis of Cyclin-Dependent Kinase and Cyclin Outlier Gene Expression Highlights CDK7 as a Potential Therapeutic Target in Chordoma
Lefler, D. S., Elliott, A., Jiang, W., Martinez‐Outschoorn, U., Al-Sabah, J., Freed, D. M., King, C. M., Maki, R. G., Riedel, R. F., Modiano, J. F., et al. (2025) · JCO Precision Oncology · doi:10.1200/po-25-00149
Repression of PRMT activities sensitize homologous recombination-proficient ovarian and breast cancer cells to PARP inhibitor treatmentPreprint
Zhang, Y., Xu, M., Yuan, J., Hu, Z., Jiang, J., Sun, Y., Huang, J. S., Wang, Y., Wang, B., Shen, J., et al. (2025) · eLife · doi:10.7554/elife.99225.2
The CIC::DUX4 oncoprotein maintains DNA integrity through direct regulation of the catalytic subunit of DNA polymerase epsilon (POLE)
Kosibaty, Z., Luck, C., & Okimoto, R. A. (2025) · Oncogene · doi:10.1038/s41388-025-03507-9
Repression of PRMT activities sensitize homologous recombination-proficient ovarian and breast cancer cells to PARP inhibitor treatmentPreprint
Zhang, Y., Xu, M., Yuan, J., Hu, Z., Jiang, J., Sun, Y., Huang, J. S., Wang, Y., Wang, B., Shen, J., et al. (2025) · eLife · doi:10.7554/elife.99225.3
Additional file 4 of Loss of heterozygosity impacts MHC expression on the immune microenvironment in CDK12-mutated prostate cancer
Lautert-Dutra, W., M. Melo, C., Chaves, L. P., Crozier, C., P. Saggioro, F., B. dos Reis, R., Bayani, J., Bonatto, S. L., & Squire, J. A. (2024) · Figshare · doi:10.6084/m9.figshare.26716228
Additional file 8 of Loss of heterozygosity impacts MHC expression on the immune microenvironment in CDK12-mutated prostate cancer
Lautert-Dutra, W., M. Melo, C., Chaves, L. P., Crozier, C., P. Saggioro, F., B. dos Reis, R., Bayani, J., Bonatto, S. L., & Squire, J. A. (2024) · Figshare · doi:10.6084/m9.figshare.26716240
Additional file 6 of Loss of heterozygosity impacts MHC expression on the immune microenvironment in CDK12-mutated prostate cancer
Lautert-Dutra, W., M. Melo, C., Chaves, L. P., Crozier, C., P. Saggioro, F., B. dos Reis, R., Bayani, J., Bonatto, S. L., & Squire, J. A. (2024) · Figshare · doi:10.6084/m9.figshare.26716234
Additional file 5 of Loss of heterozygosity impacts MHC expression on the immune microenvironment in CDK12-mutated prostate cancer
Lautert-Dutra, W., M. Melo, C., Chaves, L. P., Crozier, C., P. Saggioro, F., B. dos Reis, R., Bayani, J., Bonatto, S. L., & Squire, J. A. (2024) · Figshare · doi:10.6084/m9.figshare.26716231
Additional file 3 of Loss of heterozygosity impacts MHC expression on the immune microenvironment in CDK12-mutated prostate cancer
Lautert-Dutra, W., M. Melo, C., Chaves, L. P., Crozier, C., P. Saggioro, F., B. dos Reis, R., Bayani, J., Bonatto, S. L., & Squire, J. A. (2024) · Figshare · doi:10.6084/m9.figshare.26716225
Additional file 1 of Loss of heterozygosity impacts MHC expression on the immune microenvironment in CDK12-mutated prostate cancer
Lautert-Dutra, W., M. Melo, C., Chaves, L. P., Crozier, C., P. Saggioro, F., B. dos Reis, R., Bayani, J., Bonatto, S. L., & Squire, J. A. (2024) · Figshare · doi:10.6084/m9.figshare.26716219
Additional file 9 of Loss of heterozygosity impacts MHC expression on the immune microenvironment in CDK12-mutated prostate cancer
Lautert-Dutra, W., M. Melo, C., Chaves, L. P., Crozier, C., P. Saggioro, F., B. dos Reis, R., Bayani, J., Bonatto, S. L., & Squire, J. A. (2024) · Figshare · doi:10.6084/m9.figshare.26716243
Additional file 7 of Loss of heterozygosity impacts MHC expression on the immune microenvironment in CDK12-mutated prostate cancer
Lautert-Dutra, W., M. Melo, C., Chaves, L. P., Crozier, C., P. Saggioro, F., B. dos Reis, R., Bayani, J., Bonatto, S. L., & Squire, J. A. (2024) · Figshare · doi:10.6084/m9.figshare.26716237
Additional file 2 of Loss of heterozygosity impacts MHC expression on the immune microenvironment in CDK12-mutated prostate cancer
Lautert-Dutra, W., M. Melo, C., Chaves, L. P., Crozier, C., P. Saggioro, F., B. dos Reis, R., Bayani, J., Bonatto, S. L., & Squire, J. A. (2024) · Figshare · doi:10.6084/m9.figshare.26716222
Absence of synergistic effects by CDK12/13 inhibition in combination with cisplatin or olaparib in ovarian cancer cells
Santer, F. R., Hovdar, L., Handle, F., Tsibulak, I., Wieser, V. E., Ausserlechner, M. J., Parson, W., Schnaiter, S., Zeimet, A., Marth, C., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-46634-3
Targeted and molecular therapies in Ewing sarcoma: a comprehensive review of preclinical and clinical advances
Asmar, C., Asmar, R., Awad, G., Boutros, M., Khatib, R. A., Hammad, S., Hassan, C., Mallory, N. C., & Masrouha, K. Z. (2026) · Clinical & Translational Oncology · doi:10.1007/s12094-026-04348-y
Discovery and preclinical evaluation of ZLC853 as a potential clinical candidate covalently targeting CDK12/13 kinases
Zhou, K., Zhou, L., Tien, J. C.-Y., Huang, W., Liu, W., Sun, X., Fan, B., Huang, X., Wang, J., Chang, Y., et al. (2026) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2026.07.041
Emerging Treatments in Bone Tumors: Lessons Learned from the ESMO Annual Meeting
Kotapati, S., Manoharan, M., & Palmerini, E. (2026) · Biomolecules · doi:10.3390/biom16081167
Cyclins and Cyclin‐Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer
Zheng, S., Shen, Z., Wu, Y., Huang, X., Zhang, Z., Liu, J., Wei, Q., Chen, W., Chen, Y., & Xu, L. (2026) · MedComm · doi:10.1002/mco2.70898
SNHG family lncRNAs promote Ewing sarcoma cell fitness through intronic snoRNA-guided rRNA modifications
Briones-Martín-del-Campo, M., Lee, A. G., Dinh, T., Marchand, V., Motorin, Y., Román, M., Bi, Q., Leung, S. G., Horlbeck, M. A., Sayles, L. C., et al. (2026) · NAR Cancer · doi:10.1093/narcan/zcag019
Self-citation
A guide to transcriptional cyclin‐dependent kinases in cancer
Devlin, J. R., Kyheröinen, S., & Johnstone, R. W. (2026) · FEBS Journal · doi:10.1111/febs.70731
The roles of LLPS in transcription and chromatin organization in oncofusion-driven cancers
Gherghelas, A.-M., & Toseland, C. P. (2026) · Critical Insights in Biophysics · doi:10.1080/29932203.2026.2733916
Pharmacologically targeting CDK12 induces BRCAness and synergizes with merestinib to exacerbate DNA damage in high-risk neuroblastoma
Goulding, J. R., Couwenbergh, S. T., Bekaert, S.-L., Sanders, E., Vloed, F. D., Amo-Addae, V., Eggermont, A., Wyn, J. D., Wever, K. D., Vleminckx, L., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117997
BindingDB Entry 50023310: Discovery of novel imidazo[1,2-b]pyridazine derivatives as potent covalent inhibitors of CDK12/13.
BindingDB (2026) · UC San Diego · doi:10.7270/q2r49wnh
BindingDB Entry 50015218: Noncovalent CDK12/13 dual inhibitors-based PROTACs degrade CDK12-Cyclin K complex and induce synthetic lethality with PARP inhibitor.
BindingDB (2023) · UC San Diego · doi:10.7270/q2fn1b2m
BindingDB Entry 50023458: An update on small molecule compounds targeting synthetic lethality for cancer therapy.
BindingDB (2026) · UC San Diego · doi:10.7270/q25m6bn9
BindingDB Entry 50016375: Discovery of a Highly Potent and Selective Dual PROTAC Degrader of CDK12 and CDK13.
BindingDB (2023) · UC San Diego · doi:10.7270/q2t157nq
BindingDB Entry 50013431: Synthetic Lethality through the Lens of Medicinal Chemistry.
BindingDB (2022) · UC San Diego · doi:10.7270/q2gx4g9m
BindingDB Entry 50015910: Current progress and novel strategies that target CDK12 for drug discovery.
BindingDB (2023) · UC San Diego · doi:10.7270/q28k7f2w
BindingDB Entry 50014200: Structure-activity relationship study of THZ531 derivatives enables the discovery of BSJ-01-175 as a dual CDK12/13 covalent inhibitor with efficacy in Ewing sarcoma.
BindingDB (2022) · UC San Diego · doi:10.7270/q22b92tp

Authors: Iniguez, A. B., Stolte, B., Wang, E. J., Conway, A. S., Alexe, G., Dharia, N. V., Kwiatkowski, N., Zhang, T., Abraham, B. J., Mora, J., Kalev, P., Leggett, A., Chowdhury, D., Benes, C. H., Young, R. A., Gray, N. S., & Stegmaier, K.
Affiliations: Broad Institute (US)
Boston Children's Hospital (US)
Harvard University (US)
Whitehead Institute for Biomedical Research (US)
Hospital Sant Joan de Déu Barcelona (ES)
Massachusetts General Hospital (US)
Corresponding author: Stegmaier, Kimberly
ORCID: Iniguez, Amanda Balboni
Conway, Amy Saur
Alexe, Gabriela
Dharia, Neekesh V.
Kwiatkowski, Nicholas
Zhang, Tinghu
Abraham, Brian J.
Mora, Jaume
Chowdhury, Dipanjan
Benes, Cyril H.
Young, Richard A.
Gray, Nathanael S.
Stegmaier, Kimberly
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2018-02
Volume: 33
Issue: 2
Pages: 202-216.e6
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccell.2017.12.009
PMC: PMC5846483
OpenAlex: W2784382470
Cited by: 173
References: 43
Citations by year: 2026: 18 · 2025: 16 · 2024: 25 · 2023: 20 · 2022: 22 · 2021: 24 · 2020: 25 · 2019: 15 · 2018: 8
FWCI: 13.55
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 376 d)
Locations: Cancer Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
Funders: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
National Institutes of Health (HG002668)
National Cancer Institute (1R35 CA210030)
St. Baldrick's Foundation
Dana-Farber/Harvard Cancer Center
Topics: Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: Ewing sarcoma, THZ1, synthetic lethality, DNA repair, PARP inhibitors, combination therapy, transcription inhibitors, patient-derived xenografts
MeSH terms: Synthetic Lethal Mutations, Humans, Phenylenediamines, Pyrimidines, Sarcoma, Ewing, Oncogene Proteins, Fusion, Gene Expression Regulation, Neoplastic, Cyclin-Dependent Kinases, RNA-Binding Protein EWS, Cell Line, Tumor, Cell Proliferation, Proto-Oncogene Protein c-fli-1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

EWS/FLI Confers Tumor Cell Synthetic Lethality to CDK12 Inhibition in Ewing Sarcoma

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks