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 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Systematic antibody generation and validation via tissue microarray technology leading to identification of a novel protein prognostic panel in breast cancer

Authors: Patrick C O´Leary, Sarah A Penny, Roisin T Dolan, Catherine M Kelly, Stephen F Madden, Elton Rexhepaj, Donal J Brennan, Amanda H McCann, Fredrik Pontén, Mathias Uhlén, Radoslaw Zagozdzon, Michael J Duffy, Malcolm R Kell, Karin Jirström, William M Gallagher

Published in: BMC Cancer | Issue 1/2013

Login to get access

Abstract

Background

Although omic-based discovery approaches can provide powerful tools for biomarker identification, several reservations have been raised regarding the clinical applicability of gene expression studies, such as their prohibitive cost. However, the limited availability of antibodies is a key barrier to the development of a lower cost alternative, namely a discrete collection of immunohistochemistry (IHC)-based biomarkers. The aim of this study was to use a systematic approach to generate and screen affinity-purified, mono-specific antibodies targeting progression-related biomarkers, with a view towards developing a clinically applicable IHC-based prognostic biomarker panel for breast cancer.

Methods

We examined both in-house and publicly available breast cancer DNA microarray datasets relating to invasion and metastasis, thus identifying a cohort of candidate progression-associated biomarkers. Of these, 18 antibodies were released for extended analysis. Validated antibodies were screened against a tissue microarray (TMA) constructed from a cohort of consecutive breast cancer cases (n = 512) to test the immunohistochemical surrogate signature.

Results

Antibody screening revealed 3 candidate prognostic markers: the cell cycle regulator, Anillin (ANLN); the mitogen-activated protein kinase, PDZ-Binding Kinase (PBK); and the estrogen response gene, PDZ-Domain Containing 1 (PDZK1). Increased expression of ANLN and PBK was associated with poor prognosis, whilst increased expression of PDZK1 was associated with good prognosis. A 3-marker signature comprised of high PBK, high ANLN and low PDZK1 expression was associated with decreased recurrence-free survival (p < 0.001) and breast cancer-specific survival (BCSS) (p < 0.001). This novel signature was associated with high tumour grade (p < 0.001), positive nodal status (p = 0.029), ER-negativity (p = 0.006), Her2-positivity (p = 0.036) and high Ki67 status (p < 0.001). However, multivariate Cox regression demonstrated that the signature was not a significant predictor of BCSS (HR = 6.38; 95% CI = 0.79-51.26, p = 0.082).

Conclusions

We have developed a comprehensive biomarker pathway that extends from discovery through to validation on a TMA platform. This proof-of-concept study has resulted in the identification of a novel 3-protein prognostic panel. Additional biochemical markers, interrogated using this high-throughput platform, may further augment the prognostic accuracy of this panel to a point that may allow implementation into routine clinical practice.
Appendix
Available only for authorised users
Literature
1.
Morris SR, Carey LA: Molecular profiling in breast cancer. Rev Endocr Metab Disord. 2007, 8 (3): 185-198. 10.1007/s11154-007-9035-3.CrossRefPubMed
2.
Brennan DJ, Gallagher WM: Prognostic ability of a panel of immunohistochemistry markers - retailoring of an ‘old solution’. Breast Cancer Res. 2008, 10 (1): 102-10.1186/bcr1854.CrossRefPubMedPubMedCentral
3.
Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA: Molecular portraits of human breast tumours. Nature. 2000, 406 (6797): 747-752. 10.1038/35021093.CrossRefPubMed
4.
Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001, 98 (19): 10869-10874. 10.1073/pnas.191367098.CrossRefPubMedPubMedCentral
5.
Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S: Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003, 100 (14): 8418-8423. 10.1073/pnas.0932692100.CrossRefPubMedPubMedCentral
6.
Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y: The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature. 2012, 486 (7403): 346-352.PubMedPubMedCentral
7.
Dai H, He YD, Hart AA, Mao M, Peterse HL, Marton MJ, Witteveen AT, van ’t Veer LJ: Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002, 415 (6871): 530-536. 10.1038/415530a.CrossRefPubMed
8.
Ring BZ, Seitz RS, Beck R, Shasteen WJ, Tarr SM, Cheang MC, Yoder BJ, Budd GT, Nielsen TO, Hicks DG: Novel prognostic immunohistochemical biomarker panel for estrogen receptor-positive breast cancer. J Clin Oncol. 2006, 24 (19): 3039-3047. 10.1200/JCO.2006.05.6564.CrossRefPubMed
9.
Glas AM, Floore A, Delahaye LJ, Witteveen AT, Pover RC, Bakx N, Lahti-Domenici JS, Bruinsma TJ, Warmoes MO, Bernards R: Converting a breast cancer microarray signature into a high-throughput diagnostic test. BMC Genomics. 2006, 7: 278-10.1186/1471-2164-7-278.CrossRefPubMedPubMedCentral
10.
Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner F, Walker M, Watson D, Park T: A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004, 351 (27): 2817-2826. 10.1056/NEJMoa041588.CrossRefPubMed
11.
Sparano J: TAILORx: trial assigning individualized options for treatment (Rx). Clin Breast Cancer. 2006, 7 (4): 347-350. 10.3816/CBC.2006.n.051.CrossRefPubMed
12.
Buyse M, Loi S, Viale G, Delorenzi M, Glas A, Bergh J, Lidereau R, Ellis P, van’t Veer L: Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst. 2006, 98 (17): 1183-1192. 10.1093/jnci/djj329.CrossRefPubMed
13.
van’t Veer LJ, Bernards R: Enabling personalized cancer medicine through analysis of gene-expression patterns. Nature. 2008, 452 (7187): 564-570. 10.1038/nature06915.CrossRefPubMed
14.
Brennan DJ, O’Brien SL, Fagan A, Culhane AC, Higgins DG, Duffy MJ, Gallagher WM: Application of DNA microarray technology in determining breast cancer prognosis and therapeutic response. Expert Opin Biol Ther. 2005, 5 (8): 1069-1083. 10.1517/14712598.5.8.1069.CrossRefPubMed
15.
Larsson AH, Fridberg M, Gaber A, Nodin B, Leveen P, Jonsson GB, Uhlen M, Birgisson H, Jirstrom K: Validation of podocalyxin-like protein as a biomarker of poor prognosis in colorectal cancer. BMC Cancer. 2012, 12 (1): 282-10.1186/1471-2407-12-282.CrossRefPubMedPubMedCentral
16.
Pascal LE, True LD, Campbell DS, Deutsch EW, Risk M, Coleman IM, Eichner LJ, Nelson PS, Liu AY: Correlation of mRNA and protein levels: cell type-specific gene expression of cluster designation antigens in the prostate. BMC Genomics. 2008, 9: 246-10.1186/1471-2164-9-246.CrossRefPubMedPubMedCentral
17.
Brennan DJ, O’Connor DP, Rexhepaj E, Ponten F, Gallagher WM: Antibody-based proteomics: fast-tracking molecular diagnostics in oncology. Nature Reviews Cancer. 2010, 10 (9): 605-617. 10.1038/nrc2902.CrossRefPubMed
18.
Brennan DJ, Kelly C, Rexhepaj E, Dervan PA, Duffy MJ, Gallagher WM: Contribution of DNA and tissue microarray technology to the identification and validation of biomarkers and personalised medicine in breast cancer. Cancer Genomics Proteomics. 2007, 4 (3): 121-134.PubMed
19.
Crabb SJ, Bajdik CD, Leung S, Speers CH, Kennecke H, Huntsman DG, Gelmon KA: Can clinically relevant prognostic subsets of breast cancer patients with four or more involved axillary lymph nodes be identified through immunohistochemical biomarkers? A tissue microarray feasibility study. Breast Cancer Res. 2008, 10 (1): R6-10.1186/bcr1847.CrossRefPubMedPubMedCentral
20.
Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, Perou CM, Nielsen TO: Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res. 2008, 14 (5): 1368-1376. 10.1158/1078-0432.CCR-07-1658.CrossRefPubMed
21.
Caprioli RM: Deciphering protein molecular signatures in cancer tissues to aid in diagnosis, prognosis, and therapy. Cancer Res. 2005, 65 (23): 10642-10645. 10.1158/0008-5472.CAN-04-3581.CrossRefPubMed
22.
Andersson AC, Stromberg S, Backvall H, Kampf C, Uhlen M, Wester K, Ponten F: Analysis of protein expression in cell microarrays: a tool for antibody-based proteomics. J Histochem Cytochem. 2006, 54 (12): 1413-1423. 10.1369/jhc.6A7001.2006.CrossRefPubMedPubMedCentral
23.
Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L: Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004, 10 (16): 5367-5374. 10.1158/1078-0432.CCR-04-0220.CrossRefPubMed
24.
Culhane AC, Perriere G, Considine EC, Cotter TG, Higgins DG: Between-group analysis of microarray data. Bioinformatics. 2002, 18 (12): 1600-1608. 10.1093/bioinformatics/18.12.1600.CrossRefPubMed
25.
O’Brien SL, Fagan A, Fox EJ, Millikan RC, Culhane AC, Brennan DJ, McCann AH, Hegarty S, Moyna S, Duffy MJ: CENP-F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer. Int J Cancer. 2007, 120 (7): 1434-1443. 10.1002/ijc.22413.CrossRefPubMed
26.
Ma XJ, Salunga R, Tuggle JT, Gaudet J, Enright E, McQuary P, Payette T, Pistone M, Stecker K, Zhang BM: Gene expression profiles of human breast cancer progression. Proc Natl Acad Sci USA. 2003, 100 (10): 5974-5979. 10.1073/pnas.0931261100.CrossRefPubMedPubMedCentral
27.
Svensson S, Jirstrom K, Ryden L, Roos G, Emdin S, Ostrowski MC, Landberg G: ERK phosphorylation is linked to VEGFR2 expression and Ets-2 phosphorylation in breast cancer and is associated with tamoxifen treatment resistance and small tumours with good prognosis. Oncogene. 2005, 24 (27): 4370-4379. 10.1038/sj.onc.1208626.CrossRefPubMed
28.
Lanigan F, Gremel G, Hughes R, Brennan DJ, Martin F, Jirstrom K, Gallagher WM: Homeobox transcription factor muscle segment homeobox 2 (Msx2) correlates with good prognosis in breast cancer patients and induces apoptosis in vitro. Breast Cancer Res. 2010, 12 (4): R59-10.1186/bcr2621.CrossRefPubMedPubMedCentral
29.
Borgquist S, Jogi A, Ponten F, Ryden L, Brennan DJ, Jirstrom K: Prognostic impact of tumour-specific HMG-CoA reductase expression in primary breast cancer. Breast Cancer Res. 2008, 10 (5): R79-10.1186/bcr2146.CrossRefPubMedPubMedCentral
30.
31.
Uhlen M, Bjorling E, Agaton C, Szigyarto CA, Amini B, Andersen E, Andersson AC, Angelidou P, Asplund A, Asplund C: A human protein atlas for normal and cancer tissues based on antibody proteomics. Mol Cell Proteomics. 2005, 4 (12): 1920-1932. 10.1074/mcp.M500279-MCP200.CrossRefPubMed
32.
Uhlen M, Ponten F: Antibody-based proteomics for human tissue profiling. Mol Cell Proteomics. 2005, 4 (4): 384-393. 10.1074/mcp.R500009-MCP200.CrossRefPubMed
33.
Hughes L, Malone C, Chumsri S, Burger AM, McDonnell S: Characterisation of breast cancer cell lines and establishment of a novel isogenic subclone to study migration, invasion and tumourigenicity. Clin Exp Metastasis. 2008, 25 (5): 549-557. 10.1007/s10585-008-9169-z.CrossRefPubMed
34.
Douglas-Jones AG, Schmid KW, Bier B, Horgan K, Lyons K, Dallimore ND, Moneypenny IJ, Jasani B: Metallothionein expression in duct carcinoma in situ of the breast. Hum Pathol. 1995, 26 (2): 217-222. 10.1016/0046-8177(95)90040-3.CrossRefPubMed
35.
36.
Calabro A, Beissbarth T, Kuner R, Stojanov M, Benner A, Asslaber M, Ploner F, Zatloukal K, Samonigg H, Poustka A: Effects of infiltrating lymphocytes and estrogen receptor on gene expression and prognosis in breast cancer. Breast Cancer Res Treat. 2009, 116 (1): 69-77. 10.1007/s10549-008-0105-3.CrossRefPubMed
37.
Chang HY, Nuyten DS, Sneddon JB, Hastie T, Tibshirani R, Sorlie T, Dai H, He YD, van’t Veer LJ, Bartelink H: Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. Proc Natl Acad Sci USA. 2005, 102 (10): 3738-3743. 10.1073/pnas.0409462102.CrossRefPubMedPubMedCentral
38.
Chanrion M, Negre V, Fontaine H, Salvetat N, Bibeau F, Mac Grogan G, Mauriac L, Katsaros D, Molina F, Theillet C: A gene expression signature that can predict the recurrence of tamoxifen-treated primary breast cancer. Clin Cancer Res. 2008, 14 (6): 1744-1752. 10.1158/1078-0432.CCR-07-1833.CrossRefPubMedPubMedCentral
39.
Desmedt C, Giobbie-Hurder A, Neven P, Paridaens R, Christiaens MR, Smeets A, Lallemand F, Haibe-Kains B, Viale G, Gelber RD: The Gene expression Grade Index: a potential predictor of relapse for endocrine-treated breast cancer patients in the BIG 1–98 trial. BMC Med Genomics. 2009, 2: 40-10.1186/1755-8794-2-40.CrossRefPubMedPubMedCentral
40.
Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, Livasy C, Carey LA, Reynolds E, Dressler L: The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics. 2006, 7: 96-10.1186/1471-2164-7-96.CrossRefPubMedPubMedCentral
41.
Kok M, Linn SC, Van Laar RK, Jansen MP, van den Berg TM, Delahaye LJ, Glas AM, Peterse JL, Hauptmann M, Foekens JA: Comparison of gene expression profiles predicting progression in breast cancer patients treated with tamoxifen. Breast Cancer Res Treat. 2009, 113 (2): 275-283. 10.1007/s10549-008-9939-y.CrossRefPubMed
42.
Loi S, Haibe-Kains B, Desmedt C, Wirapati P, Lallemand F, Tutt AM, Gillet C, Ellis P, Ryder K, Reid JF: Predicting prognosis using molecular profiling in estrogen receptor-positive breast cancer treated with tamoxifen. BMC Genomics. 2008, 9: 239-10.1186/1471-2164-9-239.CrossRefPubMedPubMedCentral
43.
Sabatier R, Finetti P, Cervera N, Lambaudie E, Esterni B, Mamessier E, Tallet A, Chabannon C, Extra JM, Jacquemier J: A gene expression signature identifies two prognostic subgroups of basal breast cancer. Breast Cancer Res Treat. 2011, 126 (2): 407-420. 10.1007/s10549-010-0897-9.CrossRefPubMed
44.
Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP: Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003, 4 (2): 249-264. 10.1093/biostatistics/4.2.249.CrossRefPubMed
45.
46.
Yang YH, Dudoit S, Luu P, Lin DM, Peng V, Ngai J, Speed TP: Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res. 2002, 30 (4): e15-10.1093/nar/30.4.e15.CrossRefPubMedPubMedCentral
47.
Maglott D, Ostell J, Pruitt KD, Tatusova T: Entrez Gene: gene-centered information at NCBI. Nucleic Acids Res. 2005, 33: D54-58. 10.1093/nar/gni052.CrossRefPubMed
48.
49.
50.
Sotiriou C, Neo SY, McShane LM, Korn EL, Long PM, Jazaeri A, Martiat P, Fox SB, Harris AL, Liu ET: Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci USA. 2003, 100 (18): 10393-10398. 10.1073/pnas.1732912100.CrossRefPubMedPubMedCentral
51.
Sotiriou C, Piccart MJ: Taking gene-expression profiling to the clinic: when will molecular signatures become relevant to patient care?. Nature reviews. 2007, 7 (7): 545-553. 10.1038/nrc2173.PubMed
52.
Anders CK, Deal AM, Miller CR, Khorram C, Meng H, Burrows E, Livasy C, Fritchie K, Ewend MG, Perou CM: The prognostic contribution of clinical breast cancer subtype, age, and race among patients with breast cancer brain metastases. Cancer. 2011, 117 (8): 1602-11. 10.1002/cncr.25746.CrossRefPubMed
53.
Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S: Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006, 295 (21): 2492-2502. 10.1001/jama.295.21.2492.CrossRefPubMed
54.
Millikan RC, Newman B, Tse CK, Moorman PG, Conway K, Dressler LG, Smith LV, Labbok MH, Geradts J, Bensen JT: Epidemiology of basal-like breast cancer. Breast Cancer Res Treat. 2008, 109 (1): 123-139. 10.1007/s10549-007-9632-6.CrossRefPubMed
55.
Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Moher D, Rennie D, de Vet HC, Lijmer JG: The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Ann Intern Med. 2003, 138 (1): W1-12. 10.7326/0003-4819-138-1-200301070-00012-w1.CrossRefPubMed
56.
Silverman-Gavrila RV, Hales KG, Wilde A: Anillin-mediated targeting of peanut to pseudocleavage furrows is regulated by the GTPase Ran. Mol Biol Cell. 2008, 19 (9): 3735-3744. 10.1091/mbc.E08-01-0049.CrossRefPubMedPubMedCentral
57.
Piekny AJ, Glotzer M: Anillin is a scaffold protein that links RhoA, actin, and myosin during cytokinesis. Curr Biol. 2008, 18 (1): 30-36. 10.1016/j.cub.2007.11.068.CrossRefPubMed
58.
59.
60.
Suzuki C, Daigo Y, Ishikawa N, Kato T, Hayama S, Ito T, Tsuchiya E, Nakamura Y: ANLN plays a critical role in human lung carcinogenesis through the activation of RHOA and by involvement in the phosphoinositide 3-kinase/AKT pathway. Cancer Res. 2005, 65 (24): 11314-11325. 10.1158/0008-5472.CAN-05-1507.CrossRefPubMed
61.
Ayllon V, O’Connor R: PBK/TOPK promotes tumour cell proliferation through p38 MAPK activity and regulation of the DNA damage response. Oncogene. 2007, 26 (24): 3451-3461. 10.1038/sj.onc.1210142.CrossRefPubMed
62.
Hu F, Gartenhaus RB, Eichberg D, Liu Z, Fang HB, Rapoport AP: PBK/TOPK interacts with the DBD domain of tumor suppressor p53 and modulates expression of transcriptional targets including p21. Oncogene. 2010, 29 (40): 546-5474.CrossRef
63.
Shih MC, Chen JY, Wu YC, Jan YH, Yang BM, Lu PJ, Cheng HC, Huang MS, Yang CJ, Hsiao M: TOPK/PBK promotes cell migration via modulation of the PI3K/PTEN/AKT pathway and is associated with poor prognosis in lung cancer. Oncogene. 2012, 31 (19): 2389-2400. 10.1038/onc.2011.419.CrossRefPubMed
64.
Fukukawa C, Ueda K, Nishidate T, Katagiri T, Nakamura Y: Critical roles of LGN/GPSM2 phosphorylation by PBK/TOPK in cell division of breast cancer cells. Genes Chromosomes Cancer. 2010, 49 (10): 861-872. 10.1002/gcc.20795.CrossRefPubMed
65.
Kocher O, Krieger M: Role of the adaptor protein PDZK1 in controlling the HDL receptor SR-BI. Curr Opin Lipidol. 2009, 20 (3): 236-241. 10.1097/MOL.0b013e32832aee82.CrossRefPubMedPubMedCentral
66.
Ghosh MG, Thompson DA, Weigel RJ: PDZK1 and GREB1 are estrogen-regulated genes expressed in hormone-responsive breast cancer. Cancer Res. 2000, 60 (22): 6367-6375.PubMed
Metadata
Title
Systematic antibody generation and validation via tissue microarray technology leading to identification of a novel protein prognostic panel in breast cancer
Authors
Patrick C O´Leary
Sarah A Penny
Roisin T Dolan
Catherine M Kelly
Stephen F Madden
Elton Rexhepaj
Donal J Brennan
Amanda H McCann
Fredrik Pontén
Mathias Uhlén
Radoslaw Zagozdzon
Michael J Duffy
Malcolm R Kell
Karin Jirström
William M Gallagher
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-175

Other articles of this Issue 1/2013

BMC Cancer 1/2013 Go to the issue

Research article

Joint pain severity predicts premature discontinuation of aromatase inhibitors in breast cancer survivors

Research article

Post-diagnosis hemoglobin change associates with overall survival of multiple malignancies – results from a 14-year hospital-based cohort of lung, breast, colorectal, and liver cancers

Research article

Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine

Research article

A population-based study of rates of childbirth in recurrence-free female young adult survivors of Non-gynecologic malignancies

Research article

Derepression of Cancer/Testis Antigens in cancer is associated with distinct patterns of DNA Hypomethylation

Research article

Connexin-43 can delay early recurrence and metastasis in patients with hepatitis B-related hepatocellular carcinoma and low serum alpha-fetoprotein after radical hepatectomy
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