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Breast Cancer Research
Published in: Breast Cancer Research 1/2018

Open Access 01-12-2018 | Research article

Foxf2 plays a dual role during transforming growth factor beta-induced epithelial to mesenchymal transition by promoting apoptosis yet enabling cell junction dissolution and migration

Authors: Nathalie Meyer-Schaller, Chantal Heck, Stefanie Tiede, Mahmut Yilmaz, Gerhard Christofori

Published in: Breast Cancer Research | Issue 1/2018

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Abstract

Background

The most life-threatening step during malignant tumor progression is reached when cancer cells leave the primary tumor mass and seed metastasis in distant organs. To infiltrate the surrounding tissue and disseminate throughout the body, single motile tumor cells leave the tumor mass by breaking down cell-cell contacts in a process called epithelial to mesenchymal transition (EMT). An EMT is a complex molecular and cellular program enabling epithelial cells to abandon their differentiated phenotype, including cell-cell adhesion and cell polarity, and to acquire mesenchymal features and invasive properties.

Methods

We employed gene expression profiling and functional experiments to study transcriptional control of transforming growth factor (TGF)β-induced EMT in normal murine mammary gland epithelial (NMuMG) cells.

Results

We identified that expression of the transcription factor forkhead box protein F2 (Foxf2) is upregulated during the EMT process. Although it is not required to gain mesenchymal markers, Foxf2 is essential for the disruption of cell junctions and the downregulation of epithelial markers in NMuMG cells treated with TGFβ. Foxf2 is critical for the downregulation of E-cadherin by promoting the expression of the transcriptional repressors of E-cadherin, Zeb1 and Zeb2, while repressing expression of the epithelial maintenance factor Id2 and miRNA 200 family members. Moreover, Foxf2 is required for TGFβ-mediated apoptosis during EMT by the transcriptional activation of the proapoptotic BH3-only protein Noxa and by the negative regulation of epidermal growth factor receptor (EGFR)-mediated survival signaling through direct repression of its ligands betacellulin and amphiregulin. The dual function of Foxf2 during EMT is underscored by the finding that high Foxf2 expression correlates with good prognosis in patients with early noninvasive stages of breast cancer, but with poor prognosis in advanced breast cancer.

Conclusions

Our data identify the transcription factor Foxf2 as one of the important regulators of EMT, displaying a dual function in promoting tumor cell apoptosis as well as tumor cell migration.
Appendix
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Literature
1.
Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008;14(6):818–29.CrossRef
2.
Kalluri R. EMT: when epithelial cells decide to become mesenchymal-like cells. J Clin Invest. 2009;119(6):1417–9.CrossRef
3.
Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871–90.CrossRef
4.
Chaffer CL, San Juan BP, Lim E, Weinberg RA. EMT, cell plasticity and metastasis. Cancer Metastasis Rev. 2016;35(4):645–54.CrossRef
5.
Nieto MA. Epithelial plasticity: a common theme in embryonic and cancer cells. Science. 2013;342(6159):1234850.CrossRef
6.
Bloushtain-Qimron N, Yao J, Snyder EL, Shipitsin M, Campbell LL, Mani SA, Hu M, Chen H, Ustyansky V, Antosiewicz JE, et al. Cell type-specific DNA methylation patterns in the human breast. Proc Natl Acad Sci U S A. 2008;105(37):14076–81.CrossRef
7.
Shipitsin M, Campbell L, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, Nikolskaya T, Serebryiskaya T, Beroukhim R, Hu M, et al. Molecular definition of breast tumor heterogeneity. Cancer Cell. 2007;11(3):259–73.CrossRef
8.
Graff JR, Gabrielson E, Fujii H, Baylin SB, Herman JG. Methylation patterns of the E-cadherin 5' CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression. J Biol Chem. 2000;275(4):2727–32.CrossRef
9.
Shipitsin M, Polyak K. The cancer stem cell hypothesis: in search of definitions, markers, and relevance. Lab Invest. 2008;88(5):459–63.CrossRef
10.
Brabletz T, Hlubek F, Spaderna S, Schmalhofer O, Hiendlmeyer E, Jung A, Kirchner T. Invasion and metastasis in colorectal cancer: epithelial-mesenchymal transition, mesenchymal-epithelial transition, stem cells and beta-catenin. Cells Tissues Organs. 2005;179(1–2):56–65.CrossRef
11.
Chaffer C, Thompson E, Williams E. Mesenchymal to epithelial transition in development and disease. Cells Tissues Organs. 2007;185(1–3):7–19.CrossRef
12.
Ocana OH, Corcoles R, Fabra A, Moreno-Bueno G, Acloque H, Vega S, Barrallo-Gimeno A, Cano A, Nieto MA. Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell. 2012;22(6):709–24.CrossRef
13.
Tsai JH, Donaher JL, Murphy DA, Chau S, Yang J. Spatiotemporal regulation of epithelial-mesenchymal transition is essential for squamous cell carcinoma metastasis. Cancer Cell. 2012;22(6):725–36.CrossRef
14.
Fischer KR, Durrans A, Lee S, Sheng J, Li F, Wong ST, Choi H, El Rayes T, Ryu S, Troeger J, et al. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature. 2015;527(7579):472–6.CrossRef
15.
Zheng X, Carstens JL, Kim J, Scheible M, Kaye J, Sugimoto H, Wu CC, LeBleu VS, Kalluri R. Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature. 2015;527(7579):525–30.CrossRef
16.
Aiello NM, Brabletz T, Kang Y, Nieto MA, Weinberg RA, Stanger BZ. Upholding a role for EMT in pancreatic cancer metastasis. Nature. 2017;547(7661):E7–8.CrossRef
17.
Ye X, Brabletz T, Kang Y, Longmore GD, Nieto MA, Stanger BZ, Yang J, Weinberg RA. Upholding a role for EMT in breast cancer metastasis. Nature. 2017;547(7661):E1–3.CrossRef
18.
Krebs AM, Mitschke J, Lasierra Losada M, Schmalhofer O, Boerries M, Busch H, Boettcher M, Mougiakakos D, Reichardt W, Bronsert P, et al. The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nat Cell Biol. 2017;19(5):518–29.CrossRef
19.
Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009;9(4):265–73.CrossRef
20.
Yilmaz M, Maass D, Tiwari N, Waldmeier L, Schmidt P, Lehembre F, Christofori G. Transcription factor Dlx2 protects from TGFbeta-induced cell-cycle arrest and apoptosis. EMBO J. 2011;30(21):4489–99.CrossRef
21.
Tiwari N, Meyer-Schaller N, Arnold P, Antoniadis H, Pachkov M, van Nimwegen E, Christofori G. Klf4 is a transcriptional regulator of genes critical for EMT, including Jnk1 (Mapk8). PLoS One. 2013;8(2):e57329.CrossRef
22.
Tiwari N, Tiwari VK, Waldmeier L, Balwierz PJ, Arnold P, Pachkov M, Meyer-Schaller N, Schubeler D, van Nimwegen E, Christofori G. Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming. Cancer Cell. 2013;23(6):768–83.CrossRef
23.
Lehembre F, Yilmaz M, Wicki A, Schomber T, Strittmatter K, Ziegler D, Kren A, Went P, Derksen PW, Berns A, et al. NCAM-induced focal adhesion assembly: a functional switch upon loss of E-cadherin. EMBO J. 2008;27(19):2603–15.CrossRef
24.
Kaufmann E, Knochel W. Five years on the wings of fork head. Mech Dev. 1996;57(1):3–20.CrossRef
25.
Kaestner KH, Knochel W, Martinez DE. Unified nomenclature for the winged helix/forkhead transcription factors. Genes Dev. 2000;14(2):142–6.PubMed
26.
Wotton KR, Shimeld SM. Analysis of lamprey clustered fox genes: insight into fox gene evolution and expression in vertebrates. Gene. 2011;489(1):30–40.CrossRef
27.
Fuxe J, Vincent T, Garcia de Herreros A. Transcriptional crosstalk between TGF-beta and stem cell pathways in tumor cell invasion: role of EMT promoting Smad complexes. Cell Cycle. 2010;9(12):2363–74.CrossRef
28.
Mani SA, Yang J, Brooks M, Schwaninger G, Zhou A, Miura N, Kutok JL, Hartwell K, Richardson AL, Weinberg RA. Mesenchyme forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc Natl Acad Sci U S A. 2007;104(24):10069–74.CrossRef
29.
Taube JH, Herschkowitz JI, Komurov K, Zhou AY, Gupta S, Yang J, Hartwell K, Onder TT, Gupta PB, Evans KW, et al. Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proc Natl Acad Sci U S A. 2010;107(35):15449–54.CrossRef
30.
Bao B, Wang Z, Ali S, Kong D, Banerjee S, Ahmad A, Li Y, Azmi AS, Miele L, Sarkar FH. Over-expression of FoxM1 leads to epithelial-mesenchymal transition and cancer stem cell phenotype in pancreatic cancer cells. J Cell Biochem. 2011;112(9):2296–306.CrossRef
31.
Aitola M, Carlsson P, Mahlapuu M, Enerback S, Pelto-Huikko M. Forkhead transcription factor FoxF2 is expressed in mesodermal tissues involved in epithelio-mesenchymal interactions. Dev Dyn. 2000;218(1):136–49.CrossRef
32.
Blixt A, Mahlapuu M, Bjursell C, Darnfors C, Johannesson T, Enerback S, Carlsson P. The two-exon gene of the human forkhead transcription factor FREAC-2 (FKHL6) is located at 6p25.3. Genomics. 1998;53(3):387–90.CrossRef
33.
Hellqvist M, Mahlapuu M, Blixt A, Enerback S, Carlsson P. The human forkhead protein FREAC-2 contains two functionally redundant activation domains and interacts with TBP and TFIIB. J Biol Chem. 1998;273(36):23335–43.CrossRef
34.
Lan Y, Jiang R. Sonic hedgehog signaling regulates reciprocal epithelial-mesenchymal interactions controlling palatal outgrowth. Development. 2009;136(8):1387–96.CrossRef
35.
Katoh Y, Katoh M. Hedgehog signaling, epithelial-to-mesenchymal transition and miRNA (review). Int J Mol Med. 2008;22(3):271–5.PubMed
36.
Yu W, Ruest LB, Svoboda KK. Regulation of epithelial-mesenchymal transition in palatal fusion. Exp Biol Med (Maywood). 2009;234(5):483–91.CrossRef
37.
Wilkie AO, Morriss-Kay GM. Genetics of craniofacial development and malformation. Nat Rev Genet. 2001;2(6):458–68.CrossRef
38.
Wang T, Tamakoshi T, Uezato T, Shu F, Kanzaki-Kato N, Fu Y, Koseki H, Yoshida N, Sugiyama T, Miura N. Forkhead transcription factor Foxf2 (LUN)-deficient mice exhibit abnormal development of secondary palate. Dev Biol. 2003;259(1):83–94.CrossRef
39.
Ormestad M, Astorga J, Landgren H, Wang T, Johansson BR, Miura N, Carlsson P. Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production. Development. 2006;133(5):833–43.CrossRef
40.
Shi W, Gerster K, Alajez NM, Tsang J, Waldron L, Pintilie M, Hui AB, Sykes J, P'ng C, Miller N, et al. MicroRNA-301 mediates proliferation and invasion in human breast cancer. Cancer Res. 2011;71(8):2926–37.CrossRef
41.
Lo HW, Hsu SC, Xia W, Cao X, Shih JY, Wei Y, Abbruzzese JL, Hortobagyi GN, Hung MC. Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial-mesenchymal transition in cancer cells via up-regulation of TWIST gene expression. Cancer Res. 2007;67(19):9066–76.CrossRef
42.
Nik AM, Reyahi A, Ponten F, Carlsson P. Foxf2 in intestinal fibroblasts reduces numbers of Lgr5(+) stem cells and adenoma formation by inhibiting Wnt signaling. Gastroenterology. 2013;144(5):1001–11.CrossRef
43.
Kong PZ, Yang F, Li L, Li XQ, Feng YM. Decreased FOXF2 mRNA expression indicates early-onset metastasis and poor prognosis for breast cancer patients with histological grade II tumor. PLoS One. 2013;8(4):e61591.CrossRef
44.
Cai J, Tian AX, Wang QS, Kong PZ, Du X, Li XQ, Feng YM. FOXF2 suppresses the FOXC2-mediated epithelial-mesenchymal transition and multidrug resistance of basal-like breast cancer. Cancer Lett. 2015;367(2):129–37.CrossRef
45.
Wang QS, Kong PZ, Li XQ, Yang F, Feng YM. FOXF2 deficiency promotes epithelial-mesenchymal transition and metastasis of basal-like breast cancer. Breast Cancer Res. 2015;17:30.CrossRef
46.
Lo PK. The controversial role of forkhead box F2 (FOXF2) transcription factor in breast cancer. PRAS Open. 2017;1.
47.
Maeda M, Johnson KR, Wheelock MJ. Cadherin switching: essential for behavioral but not morphological changes during an epithelium-to-mesenchyme transition. J Cell Sci. 2005;118(Pt 5):873–87.CrossRef
48.
Deckers M, van Dinther M, Buijs J, Que I, Lowik C, van der Pluijm G, ten Dijke P. The tumor suppressor Smad4 is required for transforming growth factor beta-induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells. Cancer Res. 2006;66(4):2202–9.CrossRef
49.
Waldmeier L, Meyer-Schaller N, Diepenbruck M, Christofori G. Py2T murine breast cancer cells, a versatile model of TGFbeta-induced EMT in vitro and in vivo. PLoS One. 2012;7(11):e48651.CrossRef
50.
Hellqvist M, Mahlapuu M, Samuelsson L, Enerback S, Carlsson P. Differential activation of lung-specific genes by two forkhead proteins, FREAC-1 and FREAC-2. J Biol Chem. 1996;271(8):4482–90.CrossRef
51.
Weber M, Hellmann I, Stadler MB, Ramos L, Paabo S, Rebhan M, Schubeler D. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet. 2007;39(4):457–66.CrossRef
52.
Muller WJ, Sinn E, Pattengale PK, Wallace R, Leder P. Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell. 1988;54(1):105–15.CrossRef
53.
Derksen PW, Liu X, Saridin F, van der Gulden H, Zevenhoven J, Evers B, van Beijnum JR, Griffioen AW, Vink J, Krimpenfort P, et al. Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis. Cancer Cell. 2006;10(5):437–49.CrossRef
54.
Piek E, Moustakas A, Kurisaki A, Heldin CH, ten Dijke P. TGF-(beta) type I receptor/ALK-5 and Smad proteins mediate epithelial to mesenchymal transdifferentiation in NMuMG breast epithelial cells. J Cell Sci. 1999;112(Pt 24):4557–68.PubMed
55.
Brabletz S, Brabletz T. The ZEB/miR-200 feedback loop—a motor of cellular plasticity in development and cancer? EMBO Rep. 2010;11(9):670–7.CrossRef
56.
Caramel J, Ligier M, Puisieux A. Pleiotropic roles for ZEB1 in cancer. Cancer Res. 2018;78(1):30–5.CrossRef
57.
Gheldof A, Hulpiau P, van Roy F, De Craene B, Berx G. Evolutionary functional analysis and molecular regulation of the ZEB transcription factors. Cell Mol Life Sci. 2012;69(15):2527–41.CrossRef
58.
Kondo M, Cubillo E, Tobiume K, Shirakihara T, Fukuda N, Suzuki H, Shimizu K, Takehara K, Cano A, Saitoh M, et al. A role for Id in the regulation of TGF-beta-induced epithelial-mesenchymal transdifferentiation. Cell Death Differ. 2004;11(10):1092–101.CrossRef
59.
Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet. 2001;29(2):117–29.CrossRef
60.
Fabregat I, Herrera B, Fernandez M, Alvarez AM, Sanchez A, Roncero C, Ventura JJ, Valverde AM, Benito M. Epidermal growth factor impairs the cytochrome C/caspase-3 apoptotic pathway induced by transforming growth factor beta in rat fetal hepatocytes via a phosphoinositide 3-kinase-dependent pathway. Hepatology. 2000;32(3):528–35.CrossRef
61.
Murillo MM, del Castillo G, Sanchez A, Fernandez M, Fabregat I. Involvement of EGF receptor and c-Src in the survival signals induced by TGF-beta1 in hepatocytes. Oncogene. 2005;24(28):4580–7.CrossRef
62.
Minn A, Gupta G, Siegel P, Bos P, Shu W, Giri D, Viale A, Olshen A, Gerald W, Massague J. Genes that mediate breast cancer metastasis to lung. Nature. 2005;436(7050):518–24.CrossRef
63.
van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415(6871):530–6.CrossRef
64.
Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y, et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature. 2012;486(7403):346–52.CrossRef
65.
Dvinge H, Git A, Graf S, Salmon-Divon M, Curtis C, Sottoriva A, Zhao Y, Hirst M, Armisen J, Miska EA, et al. The shaping and functional consequences of the microRNA landscape in breast cancer. Nature. 2013;497(7449):378–82.CrossRef
66.
Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 2006;7(2):131–42.CrossRef
67.
Birchmeier W, Behrens J. Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta. 1994;1198(1):11–26.PubMed
68.
Christofori G. New signals from the invasive front. Nature. 2006;441(7092):444–50.CrossRef
69.
Kalluri R, Weinberg R. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420–8.CrossRef
70.
Peinado H, Olmeda D, Cano A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer. 2007;7(6):415–28.CrossRef
71.
Perk J, Iavarone A, Benezra R. Id family of helix-loop-helix proteins in cancer. Nat Rev Cancer. 2005;5(8):603–14.CrossRef
72.
Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008;22(7):894–907.CrossRef
73.
Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10(5):593–601.CrossRef
74.
Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, Brabletz T. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 2008;9(6):582–9.CrossRef
75.
Kundu ST, Byers LA, Peng DH, Roybal JD, Diao L, Wang J, Tong P, Creighton CJ, Gibbons DL. The miR-200 family and the miR-183~96~182 cluster target Foxf2 to inhibit invasion and metastasis in lung cancers. Oncogene. 2016;35(2):173–86.CrossRef
76.
Willis SN, Chen L, Dewson G, Wei A, Naik E, Fletcher JI, Adams JM, Huang DC. Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev. 2005;19(11):1294–305.CrossRef
77.
Kim JY, Ahn HJ, Ryu JH, Suk K, Park JH. BH3-only protein Noxa is a mediator of hypoxic cell death induced by hypoxia-inducible factor 1alpha. J Exp Med. 2004;199(1):113–24.CrossRef
78.
Ploner C, Kofler R, Villunger A. Noxa: at the tip of the balance between life and death. Oncogene. 2009;27:S84–92.CrossRef
79.
Dairkee SH, Ljung BM, Smith H, Hackett A. Immunolocalization of a human basal epithelium specific keratin in benign and malignant breast disease. Breast Cancer Res Treat. 1987;10(1):11–20.CrossRef
Metadata
Title
Foxf2 plays a dual role during transforming growth factor beta-induced epithelial to mesenchymal transition by promoting apoptosis yet enabling cell junction dissolution and migration
Authors
Nathalie Meyer-Schaller
Chantal Heck
Stefanie Tiede
Mahmut Yilmaz
Gerhard Christofori
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2018
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-018-1043-6

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