Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2022

Open Access 01-12-2022 | Metastasis | Research

Immunogenomic intertumor heterogeneity across primary and metastatic sites in a patient with lung adenocarcinoma

Authors: Runzhe Chen, Jun Li, Junya Fujimoto, Lingzhi Hong, Xin Hu, Kelly Quek, Ming Tang, Akash Mitra, Carmen Behrens, Chi-Wan Chow, Peixin Jiang, Latasha D. Little, Curtis Gumbs, Xingzhi Song, Jianhua Zhang, Dongfeng Tan, John V. Heymach, Ignacio Wistuba, P. Andrew Futreal, Don L. Gibbons, Lauren A. Byers, Jianjun Zhang, Alexandre Reuben

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2022

Login to get access

Abstract

Background

Lung cancer is the leading cause of cancer death, partially owing to its extensive heterogeneity. The analysis of intertumor heterogeneity has been limited by an inability to concurrently obtain tissue from synchronous metastases unaltered by multiple prior lines of therapy.

Methods

In order to study the relationship between genomic, epigenomic and T cell repertoire heterogeneity in a rare autopsy case from a 32-year-old female never-smoker with left lung primary late-stage lung adenocarcinoma (LUAD), we did whole-exome sequencing (WES), DNA methylation and T cell receptor (TCR) sequencing to characterize the immunogenomic landscape of one primary and 19 synchronous metastatic tumors.

Results

We observed heterogeneous mutation, methylation, and T cell patterns across distinct metastases. Only TP53 mutation was detected in all tumors suggesting an early event while other cancer gene mutations were later events which may have followed subclonal diversification. A set of prevalent T cell clonotypes were completely excluded from left-side thoracic tumors indicating distinct T cell repertoire profiles between left-side and non left-side thoracic tumors. Though a limited number of predicted neoantigens were shared, these were associated with homology of the T cell repertoire across metastases. Lastly, ratio of methylated neoantigen coding mutations was negatively associated with T-cell density, richness and clonality, suggesting neoantigen methylation may partially drive immunosuppression.

Conclusions

Our study demonstrates heterogeneous genomic and T cell profiles across synchronous metastases and how restriction of unique T cell clonotypes within an individual may differentially shape the genomic and epigenomic landscapes of synchronous lung metastases.
Appendix
Available only for authorised users
Literature
1.
Tan WL, Jain A, Takano A, Newell EW, Iyer NG, Lim WT, et al. Novel therapeutic targets on the horizon for lung cancer. Lancet Oncol. 2016;17(8):e347–e62.PubMedCrossRef
2.
Negrao MV, Quek K, Zhang J, Sepesi B. TRACERx: Tracking tumor evolution to impact the course of lung cancer. J Thorac Cardiovasc Surg. 2018;155(3):1199–202.PubMedCrossRef
3.
4.
5.
6.
Quek K, Li J, Estecio M, Zhang J, Fujimoto J, Roarty E, et al. DNA methylation intratumor heterogeneity in localized lung adenocarcinomas. Oncotarget. 2017;8(13):21994–2002.PubMedPubMedCentralCrossRef
7.
Galon J, Bruni D. Tumor immunology and tumor evolution: intertwined histories. Immunity. 2020;52(1):55–81.PubMedCrossRef
8.
De Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 2006;6(1):24–37.PubMedCrossRef
9.
Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331(6024):1565–70.PubMedCrossRef
10.
Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329–60.PubMedCrossRef
11.
McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351(6280):1463–9.PubMedPubMedCentralCrossRef
12.
Angelova M, Mlecnik B, Vasaturo A, Bindea G, Fredriksen T, Lafontaine L, et al. Evolution of metastases in space and time under immune selection. Cell. 2018;175(3):751–65.PubMedCrossRef
13.
Zhang AW, McPherson A, Milne K, Kroeger DR, Hamilton PT, Miranda A, et al. Interfaces of malignant and immunologic clonal dynamics in ovarian cancer. Cell. 2018;173(7):1755–69.PubMedCrossRef
14.
Jimenez-Sanchez A, Memon D, Pourpe S, Veeraraghavan H, Li Y, Vargas HA, et al. Heterogeneous tumor-immune microenvironments among differentially growing metastases in an ovarian cancer patient. Cell. 2017;170(5):927–38.PubMedPubMedCentralCrossRef
15.
16.
Menzies AM, Yeh I, Botton T, Bastian BC, Scolyer RA, Long GV. Clinical activity of the MEK inhibitor trametinib in metastatic melanoma containing BRAF kinase fusion. Pigment Cell Melanoma Res. 2015;28(5):607–10.PubMedPubMedCentralCrossRef
17.
Sanborn JZ, Chung J, Purdom E, Wang NJ, Kakavand H, Wilmott JS, et al. Phylogenetic analyses of melanoma reveal complex patterns of metastatic dissemination. Proc Natl Acad Sci U S A. 2015;112(35):10995–1000.PubMedPubMedCentralCrossRef
18.
Favero F, Joshi T, Marquard AM, Birkbak NJ, Krzystanek M, Li Q, et al. Sequenza: allele-specific copy number and mutation profiles from tumor sequencing data. Ann Oncol. 2015;26(1):64–70.PubMedCrossRef
19.
Cibulskis K, Lawrence MS, Carter SL, Sivachenko A, Jaffe D, Sougnez C, et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnol. 2013;31(3):213–9.PubMedPubMedCentralCrossRef
20.
Koboldt DC, Zhang Q, Larson DE, Shen D, McLellan MD, Lin L, et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res. 2012;22(3):568–76.PubMedPubMedCentralCrossRef
21.
Kim S, Scheffler K, Halpern AL, Bekritsky MA, Noh E, Kallberg M, et al. Strelka2: fast and accurate calling of germline and somatic variants. Nat Methods. 2018;15(8):591–4.PubMedCrossRef
22.
23.
Thorvaldsdottir H, Robinson JT, Mesirov JP. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform. 2013;14(2):178–92.PubMedCrossRef
24.
Jamal-Hanjani M, Wilson GA, McGranahan N, Birkbak NJ, Watkins TBK, Veeriah S, et al. Tracking the evolution of non-small-cell lung cancer. New Engl J Med. 2017;376(22):2109–21.PubMedCrossRef
25.
26.
Lundegaard C, Lamberth K, Harndahl M, Buus S, Lund O, Nielsen M. NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8-11. Nucleic Acids Res. 2008;36:W509–12.PubMedPubMedCentralCrossRef
27.
Lundegaard C, Lund O, Nielsen M. Accurate approximation method for prediction of class I MHC affinities for peptides of length 8, 10 and 11 using prediction tools trained on 9mers. Bioinformatics. 2008;24(11):1397–8.PubMedCrossRef
28.
Nielsen M, Lundegaard C, Blicher T, Lamberth K, Harndahl M, Justesen S, et al. NetMHCpan, a method for quantitative predictions of peptide binding to any HLA-A and -B locus protein of known sequence. PLoS One. 2007;2(8):e796.PubMedPubMedCentralCrossRef
29.
Turker MS. The establishment and maintenance of DNA methylation patterns in mouse somatic cells. Semin Cancer Biol. 1999;9(5):329–37.PubMedCrossRef
30.
De Meyer T, Bady P, Trooskens G, Kurscheid S, Bloch J, Kros JM, et al. Genome-wide DNA methylation detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: an independent large-scale comparison. Sci Rep. 2015;5:15375.PubMedPubMedCentralCrossRef
31.
Liu Y, Sethi NS, Hinoue T, Schneider BG, Cherniack AD, Sanchez-Vega F, et al. Comparative molecular analysis of gastrointestinal adenocarcinomas. Cancer Cell. 2018;33(4):721–35.PubMedPubMedCentralCrossRef
32.
Chakravarthy A, Furness A, Joshi K, Ghorani E, Ford K, Ward MJ, et al. Pan-cancer deconvolution of tumour composition using DNA methylation. Nat Commun. 2018;9(1):3220.PubMedPubMedCentralCrossRef
33.
Robins HS, Campregher PV, Srivastava SK, Wacher A, Turtle CJ, Kahsai O, et al. Comprehensive assessment of T-cell receptor beta-chain diversity in alphabeta T cells. Blood. 2009;114(19):4099–107.PubMedPubMedCentralCrossRef
34.
Carlson CS, Emerson RO, Sherwood AM, Desmarais C, Chung MW, Parsons JM, et al. Using synthetic templates to design an unbiased multiplex PCR assay. Nat Commun. 2013;4:2680.PubMedCrossRef
35.
Robins H, Desmarais C, Matthis J, Livingston R, Andriesen J, Reijonen H, et al. Ultra-sensitive detection of rare T cell clones. J Immunol Methods. 2012;375(1–2):14–9.PubMedCrossRef
36.
Ding L, Getz G, Wheeler DA, Mardis ER, McLellan MD, Cibulskis K, et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature. 2008;455(7216):1069–75.PubMedPubMedCentralCrossRef
37.
Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell. 2012;150(6):1107–20.PubMedPubMedCentralCrossRef
38.
Govindan R, Ding L, Griffith M, Subramanian J, Dees ND, Kanchi KL, et al. Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell. 2012;150(6):1121–34.PubMedPubMedCentralCrossRef
39.
Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–71.PubMedPubMedCentralCrossRef
40.
Cha E, Klinger M, Hou Y, Cummings C, Ribas A, Faham M, et al. Improved survival with T cell clonotype stability after anti-CTLA-4 treatment in cancer patients. Sci Transl Med. 2014;6(238):238ra70.PubMedPubMedCentralCrossRef
41.
Reuben A, Gittelman R, Zhang J, Chen R, Quek K, Vence L, et al. OA 13.05 Immune, molecular and T cell repertoire landscape of 235 resected non-small cell lung cancers and paired normal lung tissues. J Thorac Oncol. 2017;12(11):S1780.CrossRef
42.
43.
Walker R, Poleszczuk J, Pilon-Thomas S, Kim S, Anderson A, Czerniecki BJ, et al. Immune interconnectivity of anatomically distant tumors as a potential mediator of systemic responses to local therapy. Sci Rep. 2018;8(1):9474.PubMedPubMedCentralCrossRef
44.
Reuben A, Gittelman R, Gao J, Zhang J, Yusko EC, Wu CJ, et al. TCR repertoire intratumor heterogeneity in localized lung adenocarcinomas: an association with predicted neoantigen heterogeneity and postsurgical recurrence. Cancer Discov. 2017;7(10):1088–97.PubMedPubMedCentralCrossRef
45.
Baras AS, Drake C, Liu J-J, Gandhi N, Kates M, Hoque MO, et al. The ratio of CD8 to Treg tumor-infiltrating lymphocytes is associated with response to cisplatin-based neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder. Oncoimmunology. 2016;5(5):e1134412.PubMedPubMedCentralCrossRef
46.
Jordanova ES, Gorter A, Ayachi O, Prins F, Durrant LG, Kenter GG, et al. Human leukocyte antigen class I, MHC class I chain-related molecule A, and CD8+/regulatory T-cell ratio: which variable determines survival of cervical cancer patients? Clin Cancer Res. 2008;14(7):2028–35.PubMedCrossRef
47.
Qi Q, Liu Y, Cheng Y, Glanville J, Zhang D, Lee JY, et al. Diversity and clonal selection in the human T-cell repertoire. Proc Natl Acad Sci U S A. 2014;111(36):13139–44.PubMedPubMedCentralCrossRef
48.
Labelle M, Hynes RO. The initial hours of metastasis: the importance of cooperative host–tumor cell interactions during hematogenous dissemination. Cancer Discov. 2012;2(12):1091–9.PubMedPubMedCentralCrossRef
49.
50.
Robert L, Tsoi J, Wang X, Emerson R, Homet B, Chodon T, et al. CTLA4 blockade broadens the peripheral T-cell receptor repertoire. Clin Cancer Res. 2014;20(9):2424–32.PubMedPubMedCentralCrossRef
51.
Reuben A, Gittelman R, Zhang J, Quek K, Vence LM, Behrens C, et al. Association of the T-cell receptor landscape with survival in non-small cell lung cancer. J Clin Oncol. 2018;36(5):140.CrossRef
52.
Chiou S-H, Tseng D, Reuben A, Mallajosyula V, Molina IS, Conley S, et al. Global analysis of shared T cell specificities in human non-small cell lung cancer enables HLA inference and antigen discovery. Immunity. 2021;54(3):586–602.PubMedPubMedCentralCrossRef
53.
Reuben A, Zhang J, Chiou SH, Gittelman RM, Li J, Lee WC, et al. Comprehensive T cell repertoire characterization of non-small cell lung cancer. Nat Commun. 2020;11(1):603.PubMedPubMedCentralCrossRef
54.
Simoni Y, Becht E, Fehlings M, Loh CY, Koo S-L, Teng KWW, et al. Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates. Nature. 2018;557(7706):575–9.PubMedCrossRef
55.
Scheper W, Kelderman S, Fanchi LF, Linnemann C, Bendle G, de Rooij MA, et al. Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers. Nat Med. 2019;25(1):89–94.PubMedCrossRef
56.
Zhang J, Fujimoto J, Zhang J, Wedge DC, Song X, Zhang J, et al. Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science. 2014;346(6206):256–9.PubMedPubMedCentralCrossRef
57.
Lee WC, Reuben A, Hu X, McGranahan N, Chen R, Jalali A, et al. Multiomics profiling of primary lung cancers and distant metastases reveals immunosuppression as a common characteristic of tumor cells with metastatic plasticity. Genome Biol. 2020;21(1):271.PubMedPubMedCentralCrossRef
58.
Hong L, Negrao MV, Dibaj SS, Chen R, Reuben A, Bohac JM, et al. Programmed death-ligand 1 heterogeneity and its impact on benefit from immune checkpoint inhibitors in NSCLC. J Thorac Oncol. 2020;15(9):1449–59.PubMedCrossRef
59.
60.
Kim R, Keam B, Kim S, Kim M, Kim SH, Kim JW, et al. Differences in tumor microenvironments between primary lung tumors and brain metastases in lung cancer patients: therapeutic implications for immune checkpoint inhibitors. BMC Cancer. 2019;19(1):19.PubMedPubMedCentralCrossRef
61.
Vignot S, Frampton GM, Soria JC, Yelensky R, Commo F, Brambilla C, et al. Next-generation sequencing reveals high concordance of recurrent somatic alterations between primary tumor and metastases from patients with non-small-cell lung cancer. J Clin Oncol. 2013;31(17):2167–72.PubMedCrossRef
62.
Zhang J, Fujimoto J, Zhang J, Wedge DC, Song X, Zhang J, et al. Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science. 2014;346(6206):256–9.PubMedPubMedCentralCrossRef
63.
Leong TL, Gayevskiy V, Steinfort DP, De Massy MR, Gonzalez-Rajal A, Marini KD, et al. Deep multi-region whole-genome sequencing reveals heterogeneity and gene-by-environment interactions in treatment-naive, metastatic lung cancer. Oncogene. 2019;38(10):1661–75.PubMedCrossRef
64.
65.
Heyde A, Reiter JG, Naxerova K, Nowak MA. Consecutive seeding and transfer of genetic diversity in metastasis. Proc Natl Acad U S A. 2019;116(28):14129–37.CrossRef
66.
Reuben A, Spencer CN, Prieto PA, Gopalakrishnan V, Reddy SM, Miller JP, et al. Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma. NPJ Genom Med. 2017;2:10.PubMedPubMedCentralCrossRef
67.
Becerra MF, Reznik E, Redzematovic A, Tennenbaum DM, Kashan M, Ghanaat M, et al. Comparative genomic profiling of matched primary and metastatic tumors in renal cell carcinoma. Eur Urol Focus. 2018;4(6):986–94.PubMedCrossRef
68.
Lim B, Mun J, Kim JH, Kim CW, Roh SA, Cho DH, et al. Genome-wide mutation profiles of colorectal tumors and associated liver metastases at the exome and transcriptome levels. Oncotarget. 2015;6(26):22179–90.PubMedPubMedCentralCrossRef
69.
70.
Park C, Jeong K, Park JH, Jung S, Bae JM, Kim K, et al. Pan-cancer methylation analysis reveals an inverse correlation of tumor immunogenicity with methylation aberrancy. Cancer Immunol Immunother. 2021;70(6):1605–17.PubMedCrossRef
71.
Hu X, Estecio MR, Chen R, Reuben A, Wang L, Fujimoto J, et al. Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas. Nat Commun. 2021;12(1):687.PubMedPubMedCentralCrossRef
72.
Dejima H, Hu X, Chen R, Zhang J, Fujimoto J, Parra ER, et al. Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features. Nat Commun. 2021;12(1):2722.PubMedPubMedCentralCrossRef
73.
Rosenthal R, Cadieux EL, Salgado R, Al Bakir M, Moore DA, Hiley CT, et al. Neoantigen-directed immune escape in lung cancer evolution. Nature. 2019;567(7749):479–85.PubMedPubMedCentralCrossRef
74.
Liu M, Zhou J, Chen Z, Cheng AS. Understanding the epigenetic regulation of tumours and their microenvironments: opportunities and problems for epigenetic therapy. J Pathol. 2017;241(1):10–24.PubMedCrossRef
75.
Jung H, Kim HS, Kim JY, Sun JM, Ahn JS, Ahn MJ, et al. DNA methylation loss promotes immune evasion of tumours with high mutation and copy number load. Nat Commun. 2019;10(1):4278.PubMedPubMedCentralCrossRef
76.
Davoli T, Uno H, Wooten EC, Elledge SJ. Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Science. 2017;355(6322):eaaf8399.PubMedPubMedCentralCrossRef
77.
78.
Lopez-Serra L, Ballestar E, Fraga MF, Alaminos M, Setien F, Esteller M. A profile of methyl-CpG binding domain protein occupancy of hypermethylated promoter CpG islands of tumor suppressor genes in human cancer. Cancer Res. 2006;66(17):8342–6.PubMedCrossRef
79.
Coit P, Dozmorov MG, Merrill JT, McCune WJ, Maksimowicz-McKinnon K, Wren JD, et al. Epigenetic reprogramming in naive CD4+ T cells favoring T cell activation and non-Th1 effector T cell immune response as an early event in lupus flares. Arthritis Rheum. 2016;68(9):2200–9.CrossRef
80.
81.
Lee GR, Kim ST, Spilianakis CG, Fields PE, Flavell RA. T helper cell differentiation: regulation by cis elements and epigenetics. Immunity. 2006;24(4):369–79.PubMedCrossRef
82.
Caiafa P, Zampieri M. DNA methylation and chromatin structure: the puzzling CpG islands. J Cell Biochem. 2005;94(2):257–65.PubMedCrossRef
83.
Hughes T, Webb R, Fei Y, Wren J, Sawalha A. DNA methylome in human CD4+ T cells identifies transcriptionally repressive and non-repressive methylation peaks. Genes Immun. 2010;11(7):554–60.PubMedPubMedCentralCrossRef
84.
Bam M, Chintala S, Fetcko K, Williamsen BC, Siraj S, Liu S, et al. Genome wide DNA methylation landscape reveals glioblastoma’s influence on epigenetic changes in tumor infiltrating CD4+ T cells. Oncotarget. 2021;12(10):967–81.PubMedPubMedCentralCrossRef
85.
Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer. N Engl J Med. 2018;378(22):2078–92.PubMedCrossRef
86.
Hsiue EH-C, Wright KM, Douglass J, Hwang MS, Mog BJ, Pearlman AH, et al. Targeting a neoantigen derived from a common TP53 mutation. Science. 2021;371(6533):eabc8697.PubMedPubMedCentralCrossRef
87.
Lee W-C, Reuben A, Hu X, McGranahan N, Chen R, Jalali A, et al. Multiomics profiling of primary lung cancers and distant metastases reveals immunosuppression as a common characteristic of tumor cells with metastatic plasticity. Genome Biol. 2020;21(1):271.PubMedPubMedCentralCrossRef
88.
Nong J, Gong Y, Guan Y, Yi X, Yi Y, Chang L, et al. Circulating tumor DNA analysis depicts subclonal architecture and genomic evolution of small cell lung cancer. Nat Commun. 2018;9(1):3114.PubMedPubMedCentralCrossRef
89.
Lam VK, Zhang J, Wu CC, Tran HT, Li L, Diao L, et al. Genotype-specific differences in circulating tumor DNA levels in advanced NSCLC. J Thorac Oncol. 2021;16(4):601–9.PubMedCrossRef
Metadata
Title
Immunogenomic intertumor heterogeneity across primary and metastatic sites in a patient with lung adenocarcinoma
Authors
Runzhe Chen
Jun Li
Junya Fujimoto
Lingzhi Hong
Xin Hu
Kelly Quek
Ming Tang
Akash Mitra
Carmen Behrens
Chi-Wan Chow
Peixin Jiang
Latasha D. Little
Curtis Gumbs
Xingzhi Song
Jianhua Zhang
Dongfeng Tan
John V. Heymach
Ignacio Wistuba
P. Andrew Futreal
Don L. Gibbons
Lauren A. Byers
Jianjun Zhang
Alexandre Reuben
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2022
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-022-02361-x

Other articles of this Issue 1/2022

Journal of Experimental & Clinical Cancer Research 1/2022 Go to the issue

Retraction Note

Retraction Note: miR-3928v is induced by HBx via NF-κB/ EGR1 and contributes to hepatocellular carcinoma malignancy by down-regulating VDAC3

Research

microRNA-15b-5p encapsulated by M2 macrophage-derived extracellular vesicles promotes gastric cancer metastasis by targeting BRMS1 and suppressing DAPK1 transcription

Review

HER3 in cancer: from the bench to the bedside

Research

Phase 2 study of AV-GBM-1 (a tumor-initiating cell targeted dendritic cell vaccine) in newly diagnosed Glioblastoma patients: safety and efficacy assessment

Research

Dissecting super-enhancer driven transcriptional dependencies reveals novel therapeutic strategies and targets for group 3 subtype medulloblastoma

Research

hOA-DN30: a highly effective humanized single-arm MET antibody inducing remission of ‘MET-addicted’ cancers
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits