bluuebunny/crossref_metadata_2025 huggingface dataset:
Myeloid Cells Induce Infiltration and Activation of B Cells and CD4+ T Follicular Helper Cells to Sensitize Brain Metastases to Combination Immunotherapy
Authors: Ninomiya Toshifumi , Kemmotsu Naoya , Mukohara Fumiaki , Magari Masaki , Miyamoto Ai , Ueda Youki , Ishino Takamasa , Nagasaki Joji , Fujiwara Tomohiro , Yamamoto Hidetaka , Hayashi Hidetoshi , Tachibana Kota , Ishida Joji , Otani Yoshihiro , Tanaka Shota , Toyooka Shinichi , Okamoto Isamu , Togashi Yosuke
Published: January 2025

Brain metastasis (BM) is a poor prognostic factor in cancer patients. Despite showing efficacy in many extracranial tumors, immunotherapy with anti-PD-1 monoclonal antibody (mAb) or anti-CTLA-4 mAb appears to be less effective against intracranial tumors. Promisingly, recent clinical studies have reported that combination therapy with anti-PD-1 and anti-CTLA-4 mAbs has a potent antitumor effect on BM, highlighting the need to elucidate the detailed mechanisms controlling the intracranial tumor microenvironment (TME) to develop effective immunotherapeutic strategies. Here, we analyzed the tumor-infiltrating lymphocytes in murine models of BM that responded to anti-CTLA-4 mAb to anti-PD-1 mAb. Activated CD4+ T follicular helper (TFH) cells with high CTLA-4 expression characteristically infiltrated the intracranial TME, which were activated by the combination anti-CTLA-4 and anti-PD-1 treatment. Loss of TFH cells suppressed the additive effect of CTLA-4 blockade on anti-PD-1 mAb. B cell-activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) produced by abundant myeloid cells, particularly CD80hiCD206lo pro-inflammatory M1-like macrophages, in the intracranial TME, induced B cell and TFH cell infiltration and activation. Furthermore, the intracranial TME of patients with non-small cell lung cancer featured TFH and B cell infiltration as tertiary lymphoid structures. Together, these findings provide insights into the immune cell crosstalk in the intracranial TME that facilitates an additive anti-tumor effect of CTLA-4 blockade with anti-PD-1 treatment, supporting the potential of a combination immunotherapeutic strategy for BM.
Impact of Co-mutations and Transcriptional Signatures in Non–Small Cell Lung Cancer Patients Treated with Adagrasib in the KRYSTAL-1 Trial
Authors: Negrao Marcelo V. , Paula Alvaro G. , Molkentine David , Hover Laura , Nilsson Monique , Vokes Natalie , Engstrom Lars , Calinisan Andrew , Briere David M. , Waters Laura , Hallin Jill , Diao Lixia , Altan Mehmet , Blumenschein George R. , Skoulidis Ferdinandos , Wang Jing , Kopetz Scott E. , Hong David S. , Gibbons Don L. , Olson Peter , Christensen James G. , Heymach John V.
Published: January 2025

Purpose:

KRAS inhibitors are revolutionizing the treatment of non–small cell lung cancer (NSCLC), but clinico-genomic determinants of treatment efficacy warrant continued exploration.

Experimental Design:

Patients with advanced KRASG12C-mutant NSCLC treated with adagrasib [KRYSTAL-1 (NCT03785249)] were included in the analysis. Pretreatment next-generation sequencing data were collected per protocol. HTG EdgeSeq Transcriptome Panel was used for gene expression profiling. Clinical endpoints included objective response, progression-free survival (PFS), and overall survival (OS). KRASG12C-mutant NSCLC cell lines and xenograft models were used for sensitivity analyses and combination drug screens.

Results:

KEAP1 MUT and STK11MUT were associated with shorter survival to adagrasib [KEAP1: PFS 4.1 vs. 9.9 months, HR 2.7, P < 0.01; OS 5.4 vs. 19.0 months, HR 3.6, P < 0.01; STK11: PFS 4.2 vs. 11.0 months, HR 2.2, P < 0.01; OS 9.8 months vs. not reached (NR), HR 2.6, P < 0.01]. KEAP1WT/STK11WT status identified adagrasib-treated patients with significantly longer PFS (16.9 months) and OS (NR). Preclinical analyses further validate the association between KEAP1 loss of function and adagrasib resistance. Adagrasib and mTOR inhibitor combinations produced higher treatment efficacy in NSCLC models harboring STK11 and KEAP1 co-mutations. NRF2HIGH signaling was associated with shorter survival to adagrasib (PFS: 4.2 vs. 8.4 months, HR 2.0, P = 0.02; OS: 6.5 vs. 19.0 months, HR 2.8, P < 0.01) even in patients with KEAP1WT NSCLC. KEAP1WT/STK11WT/NRF2LOW status identified patients—32%—with longer survival to adagrasib (PFS 12.0 vs. 4.2 months, HR 0.2, P < 0.01; OS NR vs. 8.0 months, HR 0.1, P < 0.01).

Conclusions:

KEAP1, STK11, and NRF2 status define patients with KRASG12C-mutant NSCLC with markedly distinct outcomes to adagrasib. These results further support the use of genomic features—mutational and nonmutational—for the treatment selection of patients with KRASG12C-mutant NSCLC.
Intracellular Retention of Estradiol Is Mediated by GRAM Domain–Containing Protein ASTER-B in Breast Cancer Cells
Authors: Kim Hyung Bum , Kraus W. Lee
Published: January 2025

Elevated blood levels of estrogens have been associated with poor prognosis in estrogen receptor–positive (ER+) breast cancers, but the relationship between circulating hormone levels in the blood and intracellular hormone concentrations is not well characterized. We observed that MCF-7 cells treated acutely with 17β-estradiol (E2) retain a substantial amount of the hormone even upon the removal of the hormone from the culture medium. Moreover, global patterns of E2-dependent gene expression are sustained for hours after acute E2 treatment and hormone removal. Although circulating E2 is sequestered by sex hormone binding globulin, the potential mechanisms of intracellular E2 retention are poorly understood. We found that mislocalization of a steroid-binding GRAM domain–containing protein, ASTER-B, to the nucleus, which is observed in a subset of patients with breast cancer, is associated with higher cellular E2 retention. Accumulation and retention of E2 are related to the steroidal properties of E2 and require nuclear localization and steroid binding by ASTER-B, as shown using a panel of mutant ASTER-B proteins. Finally, we observed that nuclear ASTER-B–mediated E2 retention is required for sustained hormone-induced ERα chromatin occupancy at enhancers and gene expression, as well as subsequent cell growth responses. Our results add intracellular hormone retention as a mechanism controlling E2-dependent gene expression and downstream biological outcomes.

Implications: Mislocalized nuclear ASTER-B, which binds estradiol to support the functions of ER, can provide an alternate means of enhancing the biological effects of E2 in breast cancers and may be a potential therapeutic target that addresses multiple aspects of estrogen bioavailability.
Supplementary Table S9 from AMG 193, a Clinical Stage MTA-Cooperative PRMT5 Inhibitor, Drives Antitumor Activity Preclinically and in Patients with MTAP-Deleted Cancers
Authors: Belmontes Brian , Slemmons Katherine K. , Su Chun , Liu Siyuan , Policheni Antonia N. , Moriguchi Jodi , Tan Hong , Xie Fang , Aiello Daniel Andrew , Yang Yajing , Lazaro Raul , Aeffner Famke , Rees Matthew G. , Ronan Melissa M. , Roth Jennifer A. , Vestergaard Mikkel , Cowland Sanne , Andersson Jan , Sarvary Ian , Chen Qing , Sharma Pooja , Lopez Patricia , Tamayo Nuria , Pettus Liping H. , Ghimire-Rijal Sudipa , Mukund Susmith , Allen Jennifer R. , DeVoss Jason , Coxon Angela , Rodon Jordi , Ghiringhelli François , Penel Nicolas , Prenen Hans , Glad Sanne , Chuang Chen-Hua , Keyvanjah Kiana , Townsley Danielle M. , Butler John R. , Bourbeau Matthew P. , Caenepeel Sean , Hughes Paul E.
Published: January 2025

Supplementary Table S9: Antibodies for Flow Cytometry
Supplementary Table S8 from Cancer Prevalence across Vertebrates
Authors: Compton Zachary T. , Mellon Walker , Harris Valerie K. , Rupp Shawn , Mallo Diego , Kapsetaki Stefania E. , Wilmot Mallory , Kennington Ryan , Noble Kathleen , Baciu Cristina , Ramirez Lucia N. , Peraza Ashley , Martins Brian , Sudhakar Sushil , Aksoy Selin , Furukawa Gabriela , Vincze Orsolya , Giraudeau Mathieu , Duke Elizabeth G. , Spiro Simon , Flach Edmund , Davidson Hannah , Li Christopher I. , Zehnder Ashley , Graham Trevor A. , Troan Brigid V. , Harrison Tara M. , Tollis Marc , Schiffman Joshua D. , Aktipis C. Athena , Abegglen Lisa M. , Maley Carlo C. , Boddy Amy M.
Published: January 2025

Cell line collection and passage number information for the functional cell assays
Supplementary Table S4 from Cancer Prevalence across Vertebrates
Authors: Compton Zachary T. , Mellon Walker , Harris Valerie K. , Rupp Shawn , Mallo Diego , Kapsetaki Stefania E. , Wilmot Mallory , Kennington Ryan , Noble Kathleen , Baciu Cristina , Ramirez Lucia N. , Peraza Ashley , Martins Brian , Sudhakar Sushil , Aksoy Selin , Furukawa Gabriela , Vincze Orsolya , Giraudeau Mathieu , Duke Elizabeth G. , Spiro Simon , Flach Edmund , Davidson Hannah , Li Christopher I. , Zehnder Ashley , Graham Trevor A. , Troan Brigid V. , Harrison Tara M. , Tollis Marc , Schiffman Joshua D. , Aktipis C. Athena , Abegglen Lisa M. , Maley Carlo C. , Boddy Amy M.
Published: January 2025

Phylogenetically controlled binomial regression results
Supplementary Table S1 from Cancer Prevalence across Vertebrates
Authors: Compton Zachary T. , Mellon Walker , Harris Valerie K. , Rupp Shawn , Mallo Diego , Kapsetaki Stefania E. , Wilmot Mallory , Kennington Ryan , Noble Kathleen , Baciu Cristina , Ramirez Lucia N. , Peraza Ashley , Martins Brian , Sudhakar Sushil , Aksoy Selin , Furukawa Gabriela , Vincze Orsolya , Giraudeau Mathieu , Duke Elizabeth G. , Spiro Simon , Flach Edmund , Davidson Hannah , Li Christopher I. , Zehnder Ashley , Graham Trevor A. , Troan Brigid V. , Harrison Tara M. , Tollis Marc , Schiffman Joshua D. , Aktipis C. Athena , Abegglen Lisa M. , Maley Carlo C. , Boddy Amy M.
Published: January 2025

Mammal prevalence leaderboard
Supplementary Methods from AMG 193, a Clinical Stage MTA-Cooperative PRMT5 Inhibitor, Drives Antitumor Activity Preclinically and in Patients with MTAP-Deleted Cancers
Authors: Belmontes Brian , Slemmons Katherine K. , Su Chun , Liu Siyuan , Policheni Antonia N. , Moriguchi Jodi , Tan Hong , Xie Fang , Aiello Daniel Andrew , Yang Yajing , Lazaro Raul , Aeffner Famke , Rees Matthew G. , Ronan Melissa M. , Roth Jennifer A. , Vestergaard Mikkel , Cowland Sanne , Andersson Jan , Sarvary Ian , Chen Qing , Sharma Pooja , Lopez Patricia , Tamayo Nuria , Pettus Liping H. , Ghimire-Rijal Sudipa , Mukund Susmith , Allen Jennifer R. , DeVoss Jason , Coxon Angela , Rodon Jordi , Ghiringhelli François , Penel Nicolas , Prenen Hans , Glad Sanne , Chuang Chen-Hua , Keyvanjah Kiana , Townsley Danielle M. , Butler John R. , Bourbeau Matthew P. , Caenepeel Sean , Hughes Paul E.
Published: January 2025

Supplementary Methods: SDMA Imaging Assay, SDMA ELISA, SDMA Immunohistochemistry
Supplementary Figure S72 from Cancer Prevalence across Vertebrates
Authors: Compton Zachary T. , Mellon Walker , Harris Valerie K. , Rupp Shawn , Mallo Diego , Kapsetaki Stefania E. , Wilmot Mallory , Kennington Ryan , Noble Kathleen , Baciu Cristina , Ramirez Lucia N. , Peraza Ashley , Martins Brian , Sudhakar Sushil , Aksoy Selin , Furukawa Gabriela , Vincze Orsolya , Giraudeau Mathieu , Duke Elizabeth G. , Spiro Simon , Flach Edmund , Davidson Hannah , Li Christopher I. , Zehnder Ashley , Graham Trevor A. , Troan Brigid V. , Harrison Tara M. , Tollis Marc , Schiffman Joshua D. , Aktipis C. Athena , Abegglen Lisa M. , Maley Carlo C. , Boddy Amy M.
Published: January 2025

High resolution cladogram from Figure 6 in the main text with the species' names as tip labels
Supplementary Figure S8 from AMG 193, a Clinical Stage MTA-Cooperative PRMT5 Inhibitor, Drives Antitumor Activity Preclinically and in Patients with MTAP-Deleted Cancers
Authors: Belmontes Brian , Slemmons Katherine K. , Su Chun , Liu Siyuan , Policheni Antonia N. , Moriguchi Jodi , Tan Hong , Xie Fang , Aiello Daniel Andrew , Yang Yajing , Lazaro Raul , Aeffner Famke , Rees Matthew G. , Ronan Melissa M. , Roth Jennifer A. , Vestergaard Mikkel , Cowland Sanne , Andersson Jan , Sarvary Ian , Chen Qing , Sharma Pooja , Lopez Patricia , Tamayo Nuria , Pettus Liping H. , Ghimire-Rijal Sudipa , Mukund Susmith , Allen Jennifer R. , DeVoss Jason , Coxon Angela , Rodon Jordi , Ghiringhelli François , Penel Nicolas , Prenen Hans , Glad Sanne , Chuang Chen-Hua , Keyvanjah Kiana , Townsley Danielle M. , Butler John R. , Bourbeau Matthew P. , Caenepeel Sean , Hughes Paul E.
Published: January 2025

Supplementary Figure S8. AMG 193 treatment in BxPC-3 tumors does not affect circulating blood cells
Supplementary Figure S4 from AMG 193, a Clinical Stage MTA-Cooperative PRMT5 Inhibitor, Drives Antitumor Activity Preclinically and in Patients with MTAP-Deleted Cancers
Authors: Belmontes Brian , Slemmons Katherine K. , Su Chun , Liu Siyuan , Policheni Antonia N. , Moriguchi Jodi , Tan Hong , Xie Fang , Aiello Daniel Andrew , Yang Yajing , Lazaro Raul , Aeffner Famke , Rees Matthew G. , Ronan Melissa M. , Roth Jennifer A. , Vestergaard Mikkel , Cowland Sanne , Andersson Jan , Sarvary Ian , Chen Qing , Sharma Pooja , Lopez Patricia , Tamayo Nuria , Pettus Liping H. , Ghimire-Rijal Sudipa , Mukund Susmith , Allen Jennifer R. , DeVoss Jason , Coxon Angela , Rodon Jordi , Ghiringhelli François , Penel Nicolas , Prenen Hans , Glad Sanne , Chuang Chen-Hua , Keyvanjah Kiana , Townsley Danielle M. , Butler John R. , Bourbeau Matthew P. , Caenepeel Sean , Hughes Paul E.
Published: January 2025

Supplementary Figure S4. AM-9747 preferentially inhibits viability and SDMA signaling in MTAP-deleted tumor cells
Supplementary Figure 6 from Zongertinib (BI 1810631), an Irreversible HER2 TKI, Spares EGFR Signaling and Improves Therapeutic Response in Preclinical Models and Patients with HER2-Driven Cancers
Authors: Wilding Birgit , Woelflingseder Lydia , Baum Anke , Chylinski Krzysztof , Vainorius Gintautas , Gibson Neil , Waizenegger Irene C. , Gerlach Daniel , Augsten Martin , Spreitzer Fiona , Shirai Yukina , Ikegami Masachika , Tilandyová Sylvia , Scharn Dirk , Pearson Mark A. , Popow Johannes , Obenauf Anna C. , Yamamoto Noboru , Kondo Shunsuke , Opdam Frans L. , Bruining Annemarie , Kohsaka Shinji , Kraut Norbert , Heymach John V. , Solca Flavio , Neumüller Ralph A.
Published: January 2025

Tolerability data for zongertinib in mouse xenotransplantation assays.
Supplementary Figure S10 from AMG 193, a Clinical Stage MTA-Cooperative PRMT5 Inhibitor, Drives Antitumor Activity Preclinically and in Patients with MTAP-Deleted Cancers
Authors: Belmontes Brian , Slemmons Katherine K. , Su Chun , Liu Siyuan , Policheni Antonia N. , Moriguchi Jodi , Tan Hong , Xie Fang , Aiello Daniel Andrew , Yang Yajing , Lazaro Raul , Aeffner Famke , Rees Matthew G. , Ronan Melissa M. , Roth Jennifer A. , Vestergaard Mikkel , Cowland Sanne , Andersson Jan , Sarvary Ian , Chen Qing , Sharma Pooja , Lopez Patricia , Tamayo Nuria , Pettus Liping H. , Ghimire-Rijal Sudipa , Mukund Susmith , Allen Jennifer R. , DeVoss Jason , Coxon Angela , Rodon Jordi , Ghiringhelli François , Penel Nicolas , Prenen Hans , Glad Sanne , Chuang Chen-Hua , Keyvanjah Kiana , Townsley Danielle M. , Butler John R. , Bourbeau Matthew P. , Caenepeel Sean , Hughes Paul E.
Published: January 2025

Supplementary Figure S10. AMG 193 and sotorasib combination is synergistic in the MIAPACA2 MTAP–deleted, KRAS G12C mutant cell line
Supplementary Figure 2 from Zongertinib (BI 1810631), an Irreversible HER2 TKI, Spares EGFR Signaling and Improves Therapeutic Response in Preclinical Models and Patients with HER2-Driven Cancers
Authors: Wilding Birgit , Woelflingseder Lydia , Baum Anke , Chylinski Krzysztof , Vainorius Gintautas , Gibson Neil , Waizenegger Irene C. , Gerlach Daniel , Augsten Martin , Spreitzer Fiona , Shirai Yukina , Ikegami Masachika , Tilandyová Sylvia , Scharn Dirk , Pearson Mark A. , Popow Johannes , Obenauf Anna C. , Yamamoto Noboru , Kondo Shunsuke , Opdam Frans L. , Bruining Annemarie , Kohsaka Shinji , Kraut Norbert , Heymach John V. , Solca Flavio , Neumüller Ralph A.
Published: January 2025

Graphical NMR spectra of zongertinib and BI-3999
Supplementary Figures 1-11 from Disparate Pathways for Extrachromosomal DNA Biogenesis and Genomic DNA Repair
Authors: Rose John C. , Belk Julia A. , Wong Ivy Tsz-Lo , Luebeck Jens , Horn Hudson T. , Daniel Bence , Jones Matthew G. , Yost Kathryn E. , Hung King L. , Kolahi Kevin S. , Curtis Ellis J. , Kuo Calvin J. , Bafna Vineet , Mischel Paul S. , Chang Howard Y.
Published: January 2025

Supplementary Figure S1. PCR detects circle junctions for all MYC ecDNA guide pairs tested. Supplementary Figure S2. Hi-C contact frequency, sgRNA indel efficiency, and ecDNA circularization rates in Hap1 and K562 cells. Supplementary Figure S3. ecDNA and scar formation frequencies for initial MYC CRISPR-C guide screen. Supplementary Figure S4. Junction type and microhomology frequency in Hap1, K562, and FTE5 organoids. Supplementary Figure S5. Impact of different MH thresholds on MH frequency across loci and cell types and insertion length distribution at TCGA ecDNA junctions. Supplementary Figure S6. ATR inhibition has no impact on DHFR ecDNA or scar formation efficiency. Supplementary Figure S7. Impact of DNA-PKi and ATMi on ecDNA and scar formation efficiency and MH frequency at various loci. Supplementary Figure S8. Impact of DNA-PKi and ATMi on ecDNA and scar formation efficiency and MH frequency in K562 cells. Supplementary Figure S9. Impact of pharmacologic or genetic manipulation of DDR pathways on the most common circle and scar junction sequences for MYC ecDNA. Supplementary Figure S10. Impact of pharmacologic or genetic manipulation of DDR pathways on the most common circle and scar junction sequences for ecDNA generated from various loci. Supplementary Figure S11. A, Schematic of how the rate of DSB repair can promote or disfavor ecDNA formation. B, Schematic of two models for excisional ecDNA and scar formation.
Figure 6 from Chromothripsis-Mediated Small Cell Lung Carcinoma
Authors: Rekhtman Natasha , Tischfield Sam E. , Febres-Aldana Christopher A. , Lee Jake June-Koo , Chang Jason C. , Herzberg Benjamin O. , Selenica Pier , Woo Hyung Jun , Vanderbilt Chad M. , Yang Soo-Ryum , Xu Fei , Bowman Anita S. , da Silva Edaise M. , Noronha Anne Marie , Mandelker Diana L. , Mehine Miika , Mukherjee Semanti , Blanco-Heredia Juan , Orgera John J. , Nanjangud Gouri J. , Baine Marina K. , Aly Rania G. , Sauter Jennifer L. , Travis William D. , Savari Omid , Moreira Andre L. , Falcon Christina J. , Bodd Francis M. , Wilson Christina E. , Sienty Jacklynn V. , Manoj Parvathy , Sridhar Harsha , Wang Lu , Choudhury Noura J. , Offin Michael , Yu Helena A. , Quintanal-Villalonga Alvaro , Berger Michael F. , Ladanyi Marc , Donoghue Mark T.A. , Reis-Filho Jorge S. , Rudin Charles M.
Published: January 2025

Comparison of aSCLC vs. RB1−/TP53− nsSCLC: the dual model of SCLC pathogenesis in never-smokers. A, Lines of evidence for a histogenetic relationship between aSCLC and carcinoids or their progenitors, including histologic evidence of carcinoid histotype in at least one sample (see also Figs. 1C and 5A), expression of a lung carcinoid–specific gene OTP by IHC, or the presence of genomic alteration characteristic of carcinoids. Bottom, expression of OTP by RNA-seq and IHC. N/A, OTP IHC not available. Scale bar in OTP image: 100 μm. B, Lines of evidence for a histogenetic relationship of nsSCLC with NSCLC. C, Distribution of APOBEC mutational signature in aSCLC, nsSCLC, and sSCLC. See also Supplementary Fig. S5 and “Methods” for details. D, Expression of transcriptional subtype markers and (E) YAP1 by IHC. A, ASCL1-dominant; N, NEUROD1-dominant; P, POU2F3; TN, triple-negative. Subtype marker data were available for 15 aSCLC, 13 nsSCLC, and 142 sSCLC. F, Conceptual diagram depicting dual pathogenetic pathways underlying nsSCLC , highlighting carcinoid–SCLC pathway associated with chromothripsis vs. NSCLC–SCLC pathway associated with EGFR mutations and APOBEC signature. TSG, tumor suppressor genes. (F, created in part with BioRender.com.)
Table S4 from Combined KRAS Inhibition and Immune Therapy Generates Durable Complete Responses in an Autochthonous PDAC Model
Authors: Liu Yonghong , Han Jincheng , Hsu Wen-Hao , LaBella Kyle A. , Deng Pingna , Shang Xiaoying , Tallón de Lara Paulino , Cai Li , Jiang Shan , DePinho Ronald A.
Published: January 2025

Differential gene expression analysis of the dendritic cell population identified 29 significantly upregulated and 9 signficantly downregulated genes in iKPC PDAC tumors treated with MRTX1133 plus triple immunotherapy compared to all other treatment groups.
Figure S5 from Combined KRAS Inhibition and Immune Therapy Generates Durable Complete Responses in an Autochthonous PDAC Model
Authors: Liu Yonghong , Han Jincheng , Hsu Wen-Hao , LaBella Kyle A. , Deng Pingna , Shang Xiaoying , Tallón de Lara Paulino , Cai Li , Jiang Shan , DePinho Ronald A.
Published: January 2025

MRTX1133 treatment cooperated with triple immunotherapy to increase tumor-infiltrating CD4+ T cells.
Supplementary Tables from Early Detection of Ovarian Cancer Using Cell-Free DNA Fragmentomes and Protein Biomarkers
Authors: Medina Jamie E. , Annapragada Akshaya V. , Lof Pien , Short Sarah , Bartolomucci Adrianna L. , Mathios Dimitrios , Koul Shashikant , Niknafs Noushin , Noë Michaël , Foda Zachariah H. , Bruhm Daniel C. , Hruban Carolyn , Vulpescu Nicholas A. , Jung Euihye , Dua Renu , Canzoniero Jenna V. , Cristiano Stephen , Adleff Vilmos , Symecko Heather , van den Broek Daan , Sokoll Lori J. , Baylin Stephen B. , Press Michael F. , Slamon Dennis J. , Konecny Gottfried E. , Therkildsen Christina , Carvalho Beatriz , Meijer Gerrit A. , Andersen Claus Lindbjerg , Domchek Susan M. , Drapkin Ronny , Scharpf Robert B. , Phallen Jillian , Lok Christine A.R. , Velculescu Victor E.
Published: January 2025

Supplementary Table S1. Summary of clinical information. Supplementary Table S2. Summary of sample characteristics. Supplementary Table S3. Summary of whole-genome sequencing and fragment analyses. Supplementary Table S4. Summary of protein analyses. Supplementary Table S5. Summary of machine learning models and scores. Supplementary Table S6. Summary of performance for ovarian cancer detection.
Figure S2 from Combined KRAS Inhibition and Immune Therapy Generates Durable Complete Responses in an Autochthonous PDAC Model
Authors: Liu Yonghong , Han Jincheng , Hsu Wen-Hao , LaBella Kyle A. , Deng Pingna , Shang Xiaoying , Tallón de Lara Paulino , Cai Li , Jiang Shan , DePinho Ronald A.
Published: January 2025

PD1, LAG3, and 41BB were the predominant immune checkpoints expressed on tumor-infiltrating T cells in MRTX1133-treated iKPC PDAC tumors.
Supplementary Figures from Early Detection of Ovarian Cancer Using Cell-Free DNA Fragmentomes and Protein Biomarkers
Authors: Medina Jamie E. , Annapragada Akshaya V. , Lof Pien , Short Sarah , Bartolomucci Adrianna L. , Mathios Dimitrios , Koul Shashikant , Niknafs Noushin , Noë Michaël , Foda Zachariah H. , Bruhm Daniel C. , Hruban Carolyn , Vulpescu Nicholas A. , Jung Euihye , Dua Renu , Canzoniero Jenna V. , Cristiano Stephen , Adleff Vilmos , Symecko Heather , van den Broek Daan , Sokoll Lori J. , Baylin Stephen B. , Press Michael F. , Slamon Dennis J. , Konecny Gottfried E. , Therkildsen Christina , Carvalho Beatriz , Meijer Gerrit A. , Andersen Claus Lindbjerg , Domchek Susan M. , Drapkin Ronny , Scharpf Robert B. , Phallen Jillian , Lok Christine A.R. , Velculescu Victor E.
Published: January 2025

Supplementary Figure S1. Evaluation of screening model DELFI-Pro scores and comorbidities in individuals without cancer. Supplementary Figure S2. DELFI-Pro score evaluation in available clinical characteristics of patients with cancer. Supplementary Figure S3. Stability analysis across fold repeats and collection source. Supplementary Figure S4. Detection of ovarian cancer subtypes using DELFI-Pro screening model. Supplementary Figure S5. ROC analyses of asymptomatic individuals in the using screening or diagnostic models in the Discovery Cohort. Supplementary Figure S6. Performance of ichorCNA and median cfDNA fragment lengths in the Discovery Cohorts. Supplementary Figure S7. Detection of ovarian cancer subtypes using DELFI-Pro at high specificity. Supplementary Figure S8. Genome-wide fragmentation profiles are altered in patients in the Validation Cohort with ovarian cancer. Supplementary Figure S9. Analyses of chromosomal changes in Discovery and Validation cohorts. Supplementary Figure S10. Performance of DELFI-Pro for detection of ovarian cancer in the Validation Cohort. Supplementary Figure S11. Correlation of rank ordered DELFI-Pro scores for the Screening and Diagnostic models. Supplementary Figure S12. Assessment of DELFI-Pro in women with benign lesions. Supplementary Figure S13. Performance of DELFI-Pro for distinguishing ovarian cancer from benign masses. Supplementary Figure S14. Performance of DELFI-Pro for distinguishing ovarian cancer subtypes from benign masses. Supplementary Figure S15. Performance of DELFI-Pro for distinguishing ovarian cancer subtypes from benign masses in Validation Cohort. Supplementary Figure S16. Evaluation of overall tumor burden using the sum of reported lesion diameters. Supplementary Figure S17. Evaluation of CA1-25 and HE4 blood concentrations measured at different centers.
Figure S1 from Combined KRAS Inhibition and Immune Therapy Generates Durable Complete Responses in an Autochthonous PDAC Model
Authors: Liu Yonghong , Han Jincheng , Hsu Wen-Hao , LaBella Kyle A. , Deng Pingna , Shang Xiaoying , Tallón de Lara Paulino , Cai Li , Jiang Shan , DePinho Ronald A.
Published: January 2025

Genetic extinction of KRAS-G12D showed better anti-tumor efficacy than pharmacological inhibition of KRAS-G12D.
Table S5 from TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells
Authors: Priego Neibla , de Pablos-Aragoneses Ana , Perea-García María , Pieri Valentina , Hernández-Oliver Carolina , Álvaro-Espinosa Laura , Rojas Andrea , Sánchez Oliva , Steindl Ariane , Caleiras Eduardo , García Fernando , García-Martín Santiago , Graña-Castro Osvaldo , García-Mulero Sandra , Serrano Diego , Velasco-Beltrán Paloma , Jiménez-Lasheras Borja , Egia-Mendikute Leire , Rupp Luise , Stammberger Antonia , Meinhardt Matthias , Chaachou-Charradi Anas , Martínez-Saez Elena , Bertero Luca , Cassoni Paola , Mangherini Luca , Pellerino Alessia , Rudà Roberta , Soffietti Riccardo , Al-Shahrour Fatima , Saftig Paul , Sanz-Pamplona Rebeca , Schmitz Marc , Crocker Stephen J. , Calvo Alfonso , Palazón Asís , Valiente Manuel
Published: January 2025

Analysis of potential interactions cluster 3-cluster 7. Top 25 interactions of potential secreted and potential membrane proteins in cluster number 3 and cluster number 7 of brain metastasis associated-astrocytes considering the experimentally determined interaction. The table contains information corresponding to Supplementary Figure 1M.
Table S3 from TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells
Authors: Priego Neibla , de Pablos-Aragoneses Ana , Perea-García María , Pieri Valentina , Hernández-Oliver Carolina , Álvaro-Espinosa Laura , Rojas Andrea , Sánchez Oliva , Steindl Ariane , Caleiras Eduardo , García Fernando , García-Martín Santiago , Graña-Castro Osvaldo , García-Mulero Sandra , Serrano Diego , Velasco-Beltrán Paloma , Jiménez-Lasheras Borja , Egia-Mendikute Leire , Rupp Luise , Stammberger Antonia , Meinhardt Matthias , Chaachou-Charradi Anas , Martínez-Saez Elena , Bertero Luca , Cassoni Paola , Mangherini Luca , Pellerino Alessia , Rudà Roberta , Soffietti Riccardo , Al-Shahrour Fatima , Saftig Paul , Sanz-Pamplona Rebeca , Schmitz Marc , Crocker Stephen J. , Calvo Alfonso , Palazón Asís , Valiente Manuel
Published: January 2025

DEG cluster 7 brain metastasis-associated astrocytes. Differentially expressed genes (DEGs) found in cluster number 7 of brain metastasis associated-astrocytes. Significantly deregulated genes are highlighted. Red indicates upregulation and green indicates downregulation respect to wt condition. The table contains information corresponding to Figure 1E.
Table S21 from TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells
Authors: Priego Neibla , de Pablos-Aragoneses Ana , Perea-García María , Pieri Valentina , Hernández-Oliver Carolina , Álvaro-Espinosa Laura , Rojas Andrea , Sánchez Oliva , Steindl Ariane , Caleiras Eduardo , García Fernando , García-Martín Santiago , Graña-Castro Osvaldo , García-Mulero Sandra , Serrano Diego , Velasco-Beltrán Paloma , Jiménez-Lasheras Borja , Egia-Mendikute Leire , Rupp Luise , Stammberger Antonia , Meinhardt Matthias , Chaachou-Charradi Anas , Martínez-Saez Elena , Bertero Luca , Cassoni Paola , Mangherini Luca , Pellerino Alessia , Rudà Roberta , Soffietti Riccardo , Al-Shahrour Fatima , Saftig Paul , Sanz-Pamplona Rebeca , Schmitz Marc , Crocker Stephen J. , Calvo Alfonso , Palazón Asís , Valiente Manuel
Published: January 2025

TIMP1 levels from ELISA applied to CSF from patient samples. Levels of TIMP1 in the blood or in the cerebrospinal fluid (CSF) of non-cancer patients and brain metastasis patients from different primary tumors. Immune Cluster is shown for patients in Figure 7N. The table contains information corresponding to Figure 7L, 7N and Supplementary Figure 9A,C-D.
Table S20 from TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells
Authors: Priego Neibla , de Pablos-Aragoneses Ana , Perea-García María , Pieri Valentina , Hernández-Oliver Carolina , Álvaro-Espinosa Laura , Rojas Andrea , Sánchez Oliva , Steindl Ariane , Caleiras Eduardo , García Fernando , García-Martín Santiago , Graña-Castro Osvaldo , García-Mulero Sandra , Serrano Diego , Velasco-Beltrán Paloma , Jiménez-Lasheras Borja , Egia-Mendikute Leire , Rupp Luise , Stammberger Antonia , Meinhardt Matthias , Chaachou-Charradi Anas , Martínez-Saez Elena , Bertero Luca , Cassoni Paola , Mangherini Luca , Pellerino Alessia , Rudà Roberta , Soffietti Riccardo , Al-Shahrour Fatima , Saftig Paul , Sanz-Pamplona Rebeca , Schmitz Marc , Crocker Stephen J. , Calvo Alfonso , Palazón Asís , Valiente Manuel
Published: January 2025

Statistics of multiple experimental arms from in vivo immunotherapy experiments. Unpaired two-tailed Student’s t-test of different comparisons between the following experimental conditions: IgG2, silibinin and immune checkpoint blockade (ICB) (Anti-PD1 plus Anti-CTLA4) alone or in combination with silibinin in mice intracardially injected with B16/F10-BrM cells. Unpaired two-tailed Student’s t-test of different comparisons between the following experimental conditions: IgG2, cKOGFAP-Timp1 and immune checkpoint blockade (ICB) (Anti-PD1 plus Anti-CTLA4) alone or in combination in mice intracardially injected with E0771-BrM cells. The table contains information corresponding to Figure 7C and Supplementary Figure 8L.
Table S2 from TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells
Authors: Priego Neibla , de Pablos-Aragoneses Ana , Perea-García María , Pieri Valentina , Hernández-Oliver Carolina , Álvaro-Espinosa Laura , Rojas Andrea , Sánchez Oliva , Steindl Ariane , Caleiras Eduardo , García Fernando , García-Martín Santiago , Graña-Castro Osvaldo , García-Mulero Sandra , Serrano Diego , Velasco-Beltrán Paloma , Jiménez-Lasheras Borja , Egia-Mendikute Leire , Rupp Luise , Stammberger Antonia , Meinhardt Matthias , Chaachou-Charradi Anas , Martínez-Saez Elena , Bertero Luca , Cassoni Paola , Mangherini Luca , Pellerino Alessia , Rudà Roberta , Soffietti Riccardo , Al-Shahrour Fatima , Saftig Paul , Sanz-Pamplona Rebeca , Schmitz Marc , Crocker Stephen J. , Calvo Alfonso , Palazón Asís , Valiente Manuel
Published: January 2025

DEG cluster 3 brain metastasis-associated astrocytes. Differentially expressed genes (DEGs) found in cluster number 3 of brain metastasis associated-astrocytes. Significantly deregulated genes are highlighted. Red indicates upregulation and green indicates downregulation respect to tumor free condition. The table contains information corresponding to Figure 1D.
Table S18 from TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells
Authors: Priego Neibla , de Pablos-Aragoneses Ana , Perea-García María , Pieri Valentina , Hernández-Oliver Carolina , Álvaro-Espinosa Laura , Rojas Andrea , Sánchez Oliva , Steindl Ariane , Caleiras Eduardo , García Fernando , García-Martín Santiago , Graña-Castro Osvaldo , García-Mulero Sandra , Serrano Diego , Velasco-Beltrán Paloma , Jiménez-Lasheras Borja , Egia-Mendikute Leire , Rupp Luise , Stammberger Antonia , Meinhardt Matthias , Chaachou-Charradi Anas , Martínez-Saez Elena , Bertero Luca , Cassoni Paola , Mangherini Luca , Pellerino Alessia , Rudà Roberta , Soffietti Riccardo , Al-Shahrour Fatima , Saftig Paul , Sanz-Pamplona Rebeca , Schmitz Marc , Crocker Stephen J. , Calvo Alfonso , Palazón Asís , Valiente Manuel
Published: January 2025

Phosphoproteomic analysis of CD8+ T cells incubated with astrospheres conditioned medium. Results from phosphopeptides quantification of the LC-MS/MS analysis of CD8+ lymphocytes incubated with pSTAT3- (D1) and wt (D2) or cKOGFAP-Timp1 (D2KO) pSTAT3+ astrospheres conditioned medium. The table contains information corresponding to Figure 6K and Supplementary Figure 7A.
Table S13 from TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells
Authors: Priego Neibla , de Pablos-Aragoneses Ana , Perea-García María , Pieri Valentina , Hernández-Oliver Carolina , Álvaro-Espinosa Laura , Rojas Andrea , Sánchez Oliva , Steindl Ariane , Caleiras Eduardo , García Fernando , García-Martín Santiago , Graña-Castro Osvaldo , García-Mulero Sandra , Serrano Diego , Velasco-Beltrán Paloma , Jiménez-Lasheras Borja , Egia-Mendikute Leire , Rupp Luise , Stammberger Antonia , Meinhardt Matthias , Chaachou-Charradi Anas , Martínez-Saez Elena , Bertero Luca , Cassoni Paola , Mangherini Luca , Pellerino Alessia , Rudà Roberta , Soffietti Riccardo , Al-Shahrour Fatima , Saftig Paul , Sanz-Pamplona Rebeca , Schmitz Marc , Crocker Stephen J. , Calvo Alfonso , Palazón Asís , Valiente Manuel
Published: January 2025

Human brain metastases evaluated with multiplex. Information regarding multiplex of immune cells and quantification of TIMP1 RNAScope staining in human brain metastasis samples. The table contains information corresponding to Figure 3G.
Table S12 from TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells
Authors: Priego Neibla , de Pablos-Aragoneses Ana , Perea-García María , Pieri Valentina , Hernández-Oliver Carolina , Álvaro-Espinosa Laura , Rojas Andrea , Sánchez Oliva , Steindl Ariane , Caleiras Eduardo , García Fernando , García-Martín Santiago , Graña-Castro Osvaldo , García-Mulero Sandra , Serrano Diego , Velasco-Beltrán Paloma , Jiménez-Lasheras Borja , Egia-Mendikute Leire , Rupp Luise , Stammberger Antonia , Meinhardt Matthias , Chaachou-Charradi Anas , Martínez-Saez Elena , Bertero Luca , Cassoni Paola , Mangherini Luca , Pellerino Alessia , Rudà Roberta , Soffietti Riccardo , Al-Shahrour Fatima , Saftig Paul , Sanz-Pamplona Rebeca , Schmitz Marc , Crocker Stephen J. , Calvo Alfonso , Palazón Asís , Valiente Manuel
Published: January 2025

RENACER immune cluster evaluation. Immune cluster and gene expression of immune markers in the RENACER cohort of human brain metastasis samples. The table contains information corresponding to Supplementary Figure 4C-D.
Data from Cancer Research in the Age of Spatial Omics: Lessons from IMAXT
Authors: Bressan Dario , Walton Nicholas , Hannon Gregory J. , Al Sa’d Mohammad , Albuquerque Bruno , Ali Hamid Raza , Alini Martina , Aparicio Samuel , Ashmore Heather , Ashmore Thomas , Au Vinci , Balasubramanian Shankar , Baril Caroline , Battistoni Giorgia , Beatty Sean , Becker Robby , Bodenmiller Bernd , Bollhagen Alina , Boquetale Carla , Boyden Edward S. , Bressan Dario , Bruna Alejandra , Burger Marcel , Caldas Carlos , Callari Maurizio , Cannell Ian Gordon , Casbolt Hannah , Chornay Nick , Coutts Nikki , Dariush Ali , Deighton Lauren , Dinh Khanh N. , Duncan Natalie , Eyal-Lubling Yaniv , Falciatori Ilaria , Fan Jean , Fatemi Atefeh , Ghosh Debarati , González-Fernández Carlos , González-Solares Eduardo A. , Greenwood Wendy , Grimaldi Flaminia , Hannon Gregory J. , Harris Owen , Harris Suvi , Hemmer Nicole , Hua Kui , Irfan Melis , Jauset Cristina , Joyce Johanna A. , Kovačević Tatjana , Kuett Laura , Kunes Russell , Yoldaş Aybüke Küpcü , Lai Daniel , Laks Emma , Lee Hsuan , Lee Max , Lerda Giulia , Li Yangguang , Lovell Jack , Lu Yangning , Marioni John , McPherson Andrew , Millar Neil , Molaeinezhad Alireza , Mulvey Claire M. , Narayanan Natasha , Nogueira João C.F. , Nugent Fiona , O’Flanagan Ciara H. , Ribes Marta Paez , Pearsall Isabella , Pearsall Sarah , Pryor Brett , Qosaj Fatime , Rebbeck Clare , Roth Andrew , Rueda Oscar M. , Ruiz Teresa , Sawicka Kirsty , Sepúlveda Leonardo A. , Shah Sohrab P. , Shea Abigail , Sinha Anubhav , Smith Austin , Smith Leigh , Tavaré Simon , Vázquez-García Ignacio , Vogl Sara Lisa , Walton Nicholas A. , Watson Spencer S. , Weselak Joanna , Whitmarsh Tristan , Wild Sophia A. , Williams Elena , Windhager Jonas , Xia Chenglong , Sia Chee Ying , Zhang Chi , Zhang Ruihan , Zheng Pu , Zhuang Xiaowei
Published: January 2025

Summary:
The Imaging and Molecular Annotation of Xenografts and Tumors Cancer Grand Challenges team was set up with the objective of developing the “next generation” of pathology and cancer research by using a combination of single-cell and spatial omics tools to produce 3D molecularly annotated maps of tumors. Its activities overlapped, and in some cases catalyzed, a spatial revolution in biology that saw new technologies being deployed to investigate the roles of tumor heterogeneity and of the tumor micro-environment.

See related article by Stratton et al., p. 22

See related article by Bhattacharjee et al., p. 28

See related article by Goodwin et al., p. 34
Data from Zongertinib (BI 1810631), an Irreversible HER2 TKI, Spares EGFR Signaling and Improves Therapeutic Response in Preclinical Models and Patients with HER2-Driven Cancers
Authors: Wilding Birgit , Woelflingseder Lydia , Baum Anke , Chylinski Krzysztof , Vainorius Gintautas , Gibson Neil , Waizenegger Irene C. , Gerlach Daniel , Augsten Martin , Spreitzer Fiona , Shirai Yukina , Ikegami Masachika , Tilandyová Sylvia , Scharn Dirk , Pearson Mark A. , Popow Johannes , Obenauf Anna C. , Yamamoto Noboru , Kondo Shunsuke , Opdam Frans L. , Bruining Annemarie , Kohsaka Shinji , Kraut Norbert , Heymach John V. , Solca Flavio , Neumüller Ralph A.
Published: January 2025

Abstract
Mutations in ERBB2 (encoding HER2) occur in 2% to 4% of non–small cell lung cancer (NSCLC) and confer poor prognosis. ERBB-targeting tyrosine kinase inhibitors, approved for treating other HER2-dependent cancers, are ineffective in HER2-mutant NSCLC due to dose-limiting toxicities or suboptimal potency. We report the discovery of zongertinib (BI 1810631), a covalent HER2 inhibitor. Zongertinib potently and selectively blocks HER2, while sparing EGFR, and inhibits the growth of cells dependent on HER2 oncogenic driver events, including HER2-dependent human cancer cells resistant to trastuzumab deruxtecan. Zongertinib displays potent antitumor activity in HER2-dependent human NSCLC xenograft models and enhances the activities of antibody–drug conjugates and KRASG12C inhibitors without causing obvious toxicities. The preclinical efficacy of zongertinib translates in objective responses in patients with HER2-dependent tumors, including cholangiocarcinoma (SDC4–NRG1 fusion) and breast cancer (V777L HER2 mutation), thus supporting the ongoing clinical development of zongertinib.

Significance: HER2-mutant NSCLC poses a challenge in the clinic due to limited options for targeted therapies. Pan-ERBB blockers are limited by wild-type EGFR–mediated toxicity. Zongertinib is a highly potent and wild-type EGFR–sparing HER2 inhibitor that is active in HER2-driven tumors in the preclinical and clinical settings.
Data from Disparate Pathways for Extrachromosomal DNA Biogenesis and Genomic DNA Repair
Authors: Rose John C. , Belk Julia A. , Wong Ivy Tsz-Lo , Luebeck Jens , Horn Hudson T. , Daniel Bence , Jones Matthew G. , Yost Kathryn E. , Hung King L. , Kolahi Kevin S. , Curtis Ellis J. , Kuo Calvin J. , Bafna Vineet , Mischel Paul S. , Chang Howard Y.
Published: January 2025

Abstract
Oncogene amplification on extrachromosomal DNA (ecDNA) is a pervasive driver event in cancer, yet our understanding of how ecDNA forms is limited. In this study, we couple a CRISPR-based method for ecDNA induction with extensive characterization of newly formed ecDNAs to examine their biogenesis. We find that DNA circularization is efficient, irrespective of 3D genome context, with the formation of 800 kb, 1 Mb, and 1.8 Mb ecDNAs reaching or exceeding 15%. We show nonhomologous end joining and microhomology-mediated end joining both contribute to ecDNA formation, whereas inhibition of DNA-PK catalytic subunit and ATM have opposing impacts on ecDNA formation. ecDNA and the corresponding chromosomal excision scar can form at significantly different rates and respond differently to DNA-PK catalytic subunit and ATM inhibition. Taken together, our results support a model of ecDNA formation in which double-strand break ends dissociate from their legitimate ligation partners prior to joining of illegitimate ends to form the ecDNA and excision scar.
Significance:
Our study harnesses a CRISPR-based method to examine ecDNA biogenesis, uncovering efficient circularization between double-strand breaks. ecDNAs and their corresponding chromosomal scars can form via nonhomologous end joining or microhomology-mediated end joining, but the ecDNA and scar formation processes are distinct. Based on our findings, we establish a mechanistic model of excisional ecDNA formation.
Data from Early Detection of Ovarian Cancer Using Cell-Free DNA Fragmentomes and Protein Biomarkers
Authors: Medina Jamie E. , Annapragada Akshaya V. , Lof Pien , Short Sarah , Bartolomucci Adrianna L. , Mathios Dimitrios , Koul Shashikant , Niknafs Noushin , Noë Michaël , Foda Zachariah H. , Bruhm Daniel C. , Hruban Carolyn , Vulpescu Nicholas A. , Jung Euihye , Dua Renu , Canzoniero Jenna V. , Cristiano Stephen , Adleff Vilmos , Symecko Heather , van den Broek Daan , Sokoll Lori J. , Baylin Stephen B. , Press Michael F. , Slamon Dennis J. , Konecny Gottfried E. , Therkildsen Christina , Carvalho Beatriz , Meijer Gerrit A. , Andersen Claus Lindbjerg , Domchek Susan M. , Drapkin Ronny , Scharpf Robert B. , Phallen Jillian , Lok Christine A.R. , Velculescu Victor E.
Published: January 2025

Abstract
Ovarian cancer is a leading cause of death for women worldwide, in part due to ineffective screening methods. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome and protein biomarker [cancer antigen 125 (CA-125) and human epididymis protein 4 (HE4)] analyses to evaluate 591 women with ovarian cancer, with benign adnexal masses, or without ovarian lesions. Using a machine learning model with the combined features, we detected ovarian cancer with specificity >99% and sensitivities of 72%, 69%, 87%, and 100% for stages I to IV, respectively. At the same specificity, CA-125 alone detected 34%, 62%, 63%, and 100%, and HE4 alone detected 28%, 27%, 67%, and 100% of ovarian cancers for stages I to IV, respectively. Our approach differentiated benign masses from ovarian cancers with high accuracy (AUC = 0.88, 95% confidence interval, 0.83–0.92). These results were validated in an independent population. These findings show that integrated cfDNA fragmentome and protein analyses detect ovarian cancers with high performance, enabling a new accessible approach for noninvasive ovarian cancer screening and diagnostic evaluation.
Significance:
There is an unmet need for effective ovarian cancer screening and diagnostic approaches that enable earlier-stage cancer detection and increased overall survival. We have developed a high-performing accessible approach that evaluates cfDNA fragmentomes and protein biomarkers to detect ovarian cancer.
Suppl Figure 3 from Preclinical Development of Tuspetinib for the Treatment of Acute Myeloid Leukemia
Authors: Sonowal Himangshu , Rice William G. , Bejar Raphael , Byun Joo-Yun , Jung Seung Hyun , Sinha Ranjeet , Howell Stephen B.
Published: January 2025

Supplementary Figure 3
Dentigerous Cyst Masquerading as Lacrimal Sac Diverticulitis
Authors: Doctor Sumer , Agarwal Ayushi , Ali Mohammad Javed , Bothra Nandini
Published: January 2025

Introduction: Dentigerous cysts (DCs) involving the orbit are extremely rare. The authors report a unique case of stand-alone orbital DC associated with ectopic canine tooth masquerading as a lacrimal sac diverticulitis with superadded preseptal cellulitis. Case Presentation: A 21-year-old lady presented with left inferomedial swelling, associated with pain and redness of 1-week-duration. A lacrimal sac diverticulitis with preseptal cellulitis was suspected and imaging was requested in view of progression. Computed tomography scan of orbit revealed a well-defined heterogenous mass, with associated hyperdense lesion within the mass, prompting a possibility of a foreign body granuloma. Surgical exploration and excision confirmed the diagnosis of an ectopic canine tooth with associated DC along with excessive adhesion of the cyst to the lacrimal sac wall. Maxillary sinus did not show any abnormality. Lacrimal irrigation was patent with no recurrence noted at 6-month follow-up. Conclusion: This report highlights the presentation of DC with associated ectopic canine tooth as an isolated orbital mass, initially manifesting as preseptal cellulitis with lacrimal sac diverticulitis. Recurrent episodes of infection can lead to synechiae formation, rendering adjacent lacrimal sac more prone to injury. Cyst excision with meticulous dissection yields good outcome.