bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure 7 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

Outcome and treatment responses. A, Kaplan–Meier analysis of the disease-specific overall survival assessed from the time of diagnosis. B, Pie chart summarizing radiologic treatment response to platinum-based chemotherapy received in any line of therapy. C, Swimmer plot summarizing treatment modalities used and time-on-treatment, with time of pathologic samples collected and analysis performed indicated. CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease.
Table 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

Significantly enriched GO and pathway terms identified by GO and pathway enrichment analysis of the 29 upregulated genes identified in DCs treated with MRTX1133 plus triple immunotherapy compared to all other treatment groups.
Figure 5 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

Multisample analysis from all temporally or spatially distinct samples obtained for each patient. A, Conservation of chromothripsis and corresponding amplifications across all samples with available data from individual patients. ^ indicates lower purity samples compared with the other sample from same patient (Supplementary Table S5); CN values in such samples may be falsely low. * indicates chromothripsis detected by WGS only, but not detected by tNGS. N/A, not available: sample without NGS or IHC. Sample numbering is chronologic (Supplementary Table S3). B, Multisample analysis showing RB1 and TP53 genomic alterations and expression of pRb, p53, and p16 by IHC, illustrating a subset of patients with acquired or subclonal RB1 alterations/loss (details in Supplementary Table S1) and a subset with unusual patterns of p16 expression (see “Results”). C, Illustration of a case with acquired RB1 mutations and loss of expression in metastatic samples. pRb-positive cells admixed with negative tumor cells in panels on the right are benign lymphocytes and stromal cells, serving as internal controls. Scale bars are 100 μm, except for the left bottom, which is 1 mm. D, RNA-seq for CDKN2A, encoding p16. Arrows indicate cases with chromothripsis of chromosome 12 and ecDNA amplification of CDK4. TPM, transcripts per million. (C, created in part with BioRender.com.)
Table 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

Significantly enriched GO and pathway terms identified by GO and pathway enrichment analysis of the 216 upregulated genes identified in macrophages treated with MRTX1133 plus triple immunotherapy compared to all other treatment groups.
Figure 3 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

Chromothripsis and corresponding cancer gene amplifications and losses. A, Representative Circos plots of SVs and CNAs across the genome by WGS. Outer band shows an ideogram of chromosome positions and cytogenetic bands. Second band depicts total CN, and third band shows minor allele CN. The inner circle depicts SVs as arcs connecting the two relevant genomic points as identified by three algorithms (see “Methods”). CNAs in key cancer genes in the regions of chromothripsis (red, amplifications; blue, deletions) are displayed. Circos plots for all cases are shown in Supplementary Fig. S6. B, CN log ratio plots from the FACETS algorithm displaying the distinctive oscillating CN states on chromosomes with chromothripsis. CN segments are shown in red. Focal segments (<2 MB in size) are shown as enlarged points for visual purposes. Selected amplifications are indicated (yellow). C, Summary of chromosomal location of chromothriptic events in cases analyzed by WGS and tNGS. Also shown are selected amplifications and losses in oncogenes and tumor suppressors, respectively, localized to the chromothriptic chromosomes. Full list is provided in Supplementary Table S7. D, Schematic summary for the rate of major genomic mechanisms detected in the set analyzed by WGS (n = 11) and in the full cohort (n = 20). In the lower diagram, major chromosomes involved by chromothripsis are indicated in the inner doughnut, and corresponding recurrent gene amplifications are indicated in the outer doughnut. E, Total number of SVs identified in samples analyzed by WGS. Variants are color-coded by type. F, Number of fusions predicted in samples with available RNA-seq. G, Diagram illustrating putative enhancer hijacking in case A17 with chromothripsis on chromosome 2 resulting in translocation between SH3RF3 on chromosome 2 and upstream regulatory region of CCND1 on chromosome 11. Epigenetic landscape surrounding the breakpoint was extrapolated from data from multiple tissue types (Epilogos search tool). ChrT, chromothripsis.
Figure 2 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

Mutation and CNA landscape of aSCLC. A, Mutations and CNAs in aSCLC in comparison to the control groups of sSCLC (n = 206) and pulmonary carcinoids (n = 157) analyzed by MSK-IMPACT. OncoPrint summarizing assays performed and overall genomic features: MSI vs. MSS, TMB, and genomic signature (full signature analysis shown in Supplementary Fig. S5). Case A09 lacked a matched normal DNA sample and was therefore excluded from TMB, MSI, and signature analysis. Displayed genomic alterations include selected recurrently altered genes (see Supplementary Tables S5 and S6 for a full list of detected alterations). For patients with multiple samples, the index sample is displayed (see “Methods”). *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001. B, Expression of recurrently amplified genes by IHC in two representative cases (scale bars, 100 μm) and (C) by RNA-seq in cases with available data. Arrows in C indicate cases harboring corresponding amplifications. TPM, transcripts per million; MMR, mismatch repair; N/A, not available; MSS, microsatellite stable.
Figure S3 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

The efficacy of triple immunotherapy in iKPC mice bearing advanced PDAC.
Table S8 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

GSEA_comparision between cluster 3 and cluster 5 of brain metastasis-associated astrocytes in human brain metastasis samples. Gene set enrichment analysis (GSEA) of upregulated and downregulated signatures comparing cluster number 3 and number 5 of human brain metastasis associated-astrocytes. The table contains information corresponding to Figure 1I.
Table S7 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

STAT3-activation pathways in brain metastasis-associated astrocytes in human brain metastasis samples. Gene set enrichment analysis (GSEA) of STAT3-activation pathways in STAT3+ human brain metastasis associated-astrocytes. No significant alterations were found in cluster 3. The table contains information corresponding to Supplementary Figure 1P.
Table S6 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 metastasis samples analyzed with Chromium Fixed RNA Profiling. Clinical information of human brain metastasis samples included in Figure 1F-I.
Table S4 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

GSEA cluster 3, cluster 6 and cluster 7 of brain metastasis-associated astrocytes. Gene set enrichment analysis (GSEA) of top 25 upregulated and downregulated signatures comparing cluster number 3/6/7 of brain metastasis associated-astrocytes with the tumor free condition. The table contains information corresponding to Figure 1D-E and Supplementary Figure 1G-H.
Table S25 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

Antibodies used for flow cytometry analysis. Detailed information of antibodies used for flow cytometry.
Table S24 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

Antibodies used for multiplex immunohistochemistry. Detailed information of antibodies used for multiplex.
Table S22 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

Overall survival according to TIMP1 in the CSF. Overall survival of brain metastasis patients with different primary tumors according to their levels of TIMP1 in the cerebrospinal fluid (CSF). The table contains information corresponding to Supplementary Figure 9B.
Table S19 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 for pERK1/2 regarding their immune cluster. Information regarding multiplex of immune cells in human brain metastasis samples used for assessing pERK1/2 status in CD8+ T cells. The table contains information corresponding to Figure 6M.
Table S1 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

Astrocyte signatures. Signatures used for astrocytes annotation in the single-cell RNA sequencing of the brain metastasis-associated microenvironment using the B16/F10-BrM model. The table contains information corresponding to Figure 1B and Supplementary Figure 1C.
List of supplementary figure, supplementary tables and authors included in the RENACER signature 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

Supplementary Data file containing the list of supplementary figure legends (S1-S9) and their equivalence to the corresponding main figure and supplementary tables (Supplementary Table 1-25) with a short description as well as the authors included in the RENACER signature
Figure S9 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

Patient-derived organotypic cultures as a surrogate to assess the potential of targeting local immunosuppression in brain metastasis. Supplementary Figure 9 shows additional data corresponding to Figure 7.
Figure S8 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

A combined immunotherapy targeting local immunosuppression provides superior control of brain metastasis. Supplementary Figure 8 shows additional data corresponding to Figure 7.
Figure S7 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 binding to CD63 modulates kinase signaling in CD8+ T cells. Supplementary Figure 7 shows additional data corresponding to Figure 6.
Figure 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

TIMP1 is a downstream target of STAT3 in brain metastasis-associated astrocytes. Supplementary Figure 3 shows additional data corresponding to Figure 3.
Figure 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

STAT3-dependent immunosuppression in brain metastasis. Supplementary Figure 2 shows additional data corresponding to Figure 2.
Data 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

Abstract
One of the most robust synthetic lethal interactions observed in multiple functional genomic screens has been the dependency on protein arginine methyltransferase 5 (PRMT5) in cancer cells with MTAP deletion. We report the discovery of the clinical stage MTA-cooperative PRMT5 inhibitor AMG 193, which preferentially binds PRMT5 in the presence of MTA and has potent biochemical and cellular activity in MTAP-deleted cells across multiple cancer lineages. In vitro, PRMT5 inhibition induces DNA damage, cell cycle arrest, and aberrant alternative mRNA splicing in MTAP-deleted cells. In human cell line and patient-derived xenograft models, AMG 193 induces robust antitumor activity and is well tolerated with no impact on normal hematopoietic cell lineages. AMG 193 synergizes with chemotherapies or the KRAS G12C inhibitor sotorasib in vitro and combination treatment in vivo substantially inhibits tumor growth. AMG 193 is demonstrating promising clinical activity, including confirmed partial responses in patients with MTAP-deleted solid tumors from an ongoing phase 1/2 study.

Significance: AMG 193 preferentially inhibits the growth of MTAP-deleted tumor cells by inhibiting PRMT5 when in complex with MTA, thus sparing MTAP wild-type normal cells. AMG 193 shows promise as a targeted therapy in a clinically defined patient population.
Data 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

Abstract
Cancer is pervasive across multicellular species, but what explains the differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades of tetrapods (amphibians, sauropsids, and mammals), we found that neoplasia and malignancy prevalence increases with adult mass (contrary to Peto’s paradox) and somatic mutation rate but decreases with gestation time. The relationship between adult mass and malignancy prevalence was only apparent when we controlled for gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%), the black-footed penguin (<0.4%), ferrets (63%), and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer.

Significance: Evolution has discovered mechanisms for suppressing cancer in a wide variety of species. By analyzing veterinary necropsy records, we can identify species with exceptionally high or low cancer prevalence. Discovering the mechanisms of cancer susceptibility and resistance may help improve cancer prevention and explain cancer syndromes.

See related commentary by Metzger, p. 14
Data 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

Abstract
Small cell lung carcinoma (SCLC) is a highly aggressive malignancy that is typically associated with tobacco exposure and inactivation of RB1 and TP53 genes. Here, we performed detailed clinicopathologic, genomic, and transcriptomic profiling of an atypical subset of SCLC that lacked RB1 and TP53 co-inactivation and arose in never/light smokers. We found that most cases were associated with chromothripsis—massive, localized chromosome shattering—recurrently involving chromosome 11 or 12 and resulting in extrachromosomal amplification of CCND1 or co-amplification of CCND2/CDK4/MDM2, respectively. Uniquely, these clinically aggressive tumors exhibited genomic and pathologic links to pulmonary carcinoids, suggesting a previously uncharacterized mode of SCLC pathogenesis via transformation from lower-grade neuroendocrine tumors or their progenitors. Conversely, SCLC in never-smokers harboring inactivated RB1 and TP53 exhibited hallmarks of adenocarcinoma-to-SCLC derivation, supporting two distinct pathways of plasticity-mediated pathogenesis of SCLC in never-smokers.

Significance: Here, we provide the first detailed description of a unique SCLC subset lacking RB1/TP53 alterations and identify extensive chromothripsis and pathogenetic links to pulmonary carcinoids as its hallmark features. This work defines atypical SCLC as a novel entity among lung cancers, highlighting its exceptional histogenesis, clinicopathologic characteristics, and therapeutic vulnerabilities.

See related commentary by Nadeem and Drapkin, p. 8
Data from Visualizing Cancer Heterogeneity at the Molecular and Cellular Levels: Lessons from Rosetta
Authors: Goodwin Richard J.A. , Marshall John F. , Poulogiannis George , Yuneva Mariia , Brindle Kevin M. , Takáts Zoltán , Sansom Owen J. , Bunch Josephine , Barry Simon T. , Al-Afeef Ala , Amgheib Ala , Azarian Sara , Brochu-Williams Frederic , Burton Amy , Campbell Andrew , Cristaudo Vanina , Demircali Ali , Dexter Alex , Elia Efstathios , Fala Maria , Garrett Magali , Ghanate Avinash , Gilmore Ian , Gonzalez Ariadna , Grant Paul , Gupta Amit , Gurung Dipa , Hall Harry , Hamm Gregory , Inglese Paolo , Islam Najah , Jones Stewart , Karali Evi , Kazanc Emine , Koguna Hanifa , Kohli Manas , Koquna Hanifa , Koundouros Nikolaos , Kreuzaler Peter , Kyriazi Melina , Lall Sharanpreet Kall , Lewis David Y. , Ling Stephanie , Loizeau Xavier , Luptakova Dominika , Maneta-Stravrakaki Stefania , McGill Daniel , McKenzie James , McMahon Greg , Metodiev Martin , Mistry Jaynish , Monteiro Alvaro Perdones , Montezuma Erica , Morton Jennifer , Munteanu Catherine , Murta Teresa , Najumudeen Arafath , Nanda Chandan Seth , Nasif Ammar , Nikula Chelsea J. , Paauwe Madelon , Paiz Petra , Panina Yulia , Philip Robin , Poynter Liam , Pruski Pamela , Race Alan M. , Rao Jyotsna , Richings Jack , Savage Adele , Sharma Shreya , Soares Renata Filipe , Soloviev Dmitry , Spicer-Hadlington Amy , Sproat Caroline , Steven Rory T. , Sumpton David , Taylor Adam J. , Thomas Spencer , Thompson Daria , Tripp Aurelien , Tsalikis Thanasis , Tsyben Anastasia , Turseven Seyma , Vande-Voorde Johan , Vorng Jean-Luc , White Emma , Wright Alan , Wu Vincen , Xiang Yuchen , Yan Bin , Zao Jinshi , Zeiger Lucas , Zhang Junting , Zhou Weiwei
Published: January 2025

Summary:
Understanding tumor heterogeneity is a major challenge that was recognized as one of the first Cancer Grand Challenges, with a call to provide solutions to visualize tumor heterogeneity. The Rosetta team took on this challenge, exploiting advances in spatial-omics approaches centered around mass spectrometry imaging to map tumor heterogeneity at the cellular and molecular scales with different levels of resolution.

See related article by Bressan et al., p. 16

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

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

Abstract
Pancreatic ductal adenocarcinoma (PDAC) resists conventional chemo/radiation and immunotherapy (IO). In PDAC, oncogenic KRAS (KRAS*) drives glycolysis in cancer cells to consume available glucose and produce abundant lactate, creating profound immune suppression in the tumor microenvironment. In this study, we combined KRAS* inhibition with agents targeting the major arms of the immunity cycle: CXCR1/2 inhibitor for myeloid cells, antagonistic anti-LAG3 antibody for T cells, and agonistic anti-41BB antibody for dendritic cells. This combination elicited robust antitumor regression in iKPC mice bearing large autochthonous tumors. Whereas untreated mice succumbed within 3 weeks, sustained treatment led to durable complete tumor regression and prolonged survival in 36% of mice at 6 months. Mechanistic analyses revealed enhanced T-cell infiltration and activation, depletion of immunosuppressive myeloid cells, and increased antigen cross-presentation by dendritic cells within the tumor core. These findings highlight the promise of KRAS* inhibitors alongside IO as a potential PDAC treatment avenue, warranting clinical investigation.
Significance:
Clinically available KRAS* inhibitors and IO agents alleviated the immunosuppressive tumor microenvironment in PDAC. Profound tumor regression and prolonged survival in an autochthonous PDAC model provide a compelling rationale for combining KRAS* inhibition with IO agents targeting multiple arms of the immunity cycle to combat PDAC.
Data 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

Abstract
Immunotherapies against brain metastases have shown clinical benefits when applied to asymptomatic patients, but they are largely ineffective in symptomatic cases for unknown reasons. Here, we dissect the heterogeneity in metastasis-associated astrocytes using single-cell RNA sequencing and report a population that blocks the antitumoral activity of infiltrating T cells. This protumoral activity is mediated by the secretion of tissue inhibitor of metalloproteinase-1 (TIMP1) from a cluster of pSTAT3+ astrocytes that acts on CD63+ CD8+ T cells to modulate their function. Using genetic and pharmacologic approaches in mouse and human brain metastasis models, we demonstrate that combining immune checkpoint blockade antibodies with the inhibition of astrocyte-mediated local immunosuppression may benefit patients with symptomatic brain metastases. We further reveal that the presence of tissue inhibitor of metalloproteinase-1 in liquid biopsies provides a biomarker to select patients for this combined immunotherapy. Overall, our findings demonstrate an unexpected immunomodulatory role for astrocytes in brain metastases with clinical implications.

Significance: This study presents a significant advancement in understanding immune modulation in brain tumors and offers new insights into the potential therapeutic interventions for brain metastases.

See related commentary by Lorger and James, p. 11
Nerves at Play: The Peripheral Nervous System in Extracranial Malignancies
Authors: Vermeer Paola D. , Restaino Anthony C. , Barr Jeffrey L. , Yaniv Dan , Amit Moran
Published: January 2025

The exponential growth of the cancer neuroscience field has shown that the host’s immune, vascular, and nervous systems communicate with and influence each other in the tumor microenvironment, dictating the cancer malignant phenotype. Unraveling the nervous system’s contributions toward this phenotype brings us closer to cancer cures. In this review, we summarize the peripheral nervous system’s contributions to cancer. We highlight the effects of nerve recruitment and tumor innervation, the neuro-immune axis, glial cell activity, and neural regulation on cancer development and progression. We also discuss harnessing the neural control of peripheral cancers as a potential therapeutic approach in oncology.

Significance: The continued and growing interest in cancer neuroscience by the scientific and medical communities reflects the rapidly accumulating interdisciplinary understanding of the nervous system’s modulation of immune, vascular, and cancer cells’ functions in malignancies. Understanding these regulatory functions can identify targets for intervention that may already be clinically available for other indications. This potential brings great excitement and hope for patients with cancer worldwide.
Cancer Research in the Age of Spatial Omics: Lessons from IMAXT
Authors: Bressan Dario ,   IMAXT Cancer Grand Challenges Consortium, Walton Nicholas , Hannon Gregory J. ,   IMAXT Cancer Grand Challenges Consortium, 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

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
Implementing Mutational Epidemiology on a Global Scale: Lessons from Mutographs
Authors: Stratton Michael R. , Humphreys Laura , Alexandrov Ludmil B. , Balmain Allan , Brennan Paul , Campbell Peter J. , Phillips David H.
Published: January 2025

The Mutographs Cancer Grand Challenge team aimed to discover unknown causes of cancer through mutational epidemiology, an alliance of cancer epidemiology and somatic genomics. By generating whole-genome sequences from thousands of cancers and normal tissues from more than 30 countries on five continents, it discovered unsuspected mutagenic exposures affecting millions of people, raised the possibility that some carcinogens act by altering forces of selection in tissue microenvironments rather than by mutagenesis, and demonstrated changes to the direction of somatic evolution in normal cells of the human body in response to exogenous exposures and noncancer diseases.

See related article by Bressan et al., p. 16

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

See related article by Goodwin et al., p. 34
Supplementary Data 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

Information on antibody RRID and Other catalog numbers
Suppl Figure 5 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 5
Figure 6 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

Effect of NRASG12D expression in MV-4-11 clones on sensitivity to (A) TUS and (B) VEN (data are mean ± SEM from three-independent experiments). C, Antitumor activity of TUS, belvarafenib, and the combination of both in mice bearing MV-4-11 NRASG12D subcutaneous tumors (drugs were given once daily for 15 days via oral gavage; data are presented as mean ± SEM).
Figure 1 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

Structure of TUS and pattern of kinase inhibition. A, Structure of TUS. B, Principal kinases inhibited by TUS as determined from broad kinase screens.