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

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Molecular Cancer
Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Research

Challenging the roles of CD44 and lipolysis stimulated lipoprotein receptor in conveying Clostridium perfringens iota toxin cytotoxicity in breast cancer

Authors: Katerina D Fagan-Solis, Denise K Reaves, M Cristina Rangel, Michel R Popoff, Bradley G Stiles, Jodie M Fleming

Published in: Molecular Cancer | Issue 1/2014

Login to get access

Abstract

Background

Translational exploration of bacterial toxins has come to the forefront of research given their potential as a chemotherapeutic tool. Studies in select tissues have demonstrated that Clostridium perfringens iota toxin binds to CD44 and lipolysis stimulated lipoprotein receptor (LSR) cell-surface proteins. We recently demonstrated that LSR expression correlates with estrogen receptor positive breast cancers and that LSR signaling directs aggressive, tumor-initiating cell behaviors. Herein, we identify the mechanisms of iota toxin cytotoxicity in a tissue-specific, breast cancer model with the ultimate goal of laying the foundation for using iota toxin as a targeted breast cancer therapy.

Methods

In vitro model systems were used to determine the cytotoxic effect of iota toxin on breast cancer intrinsic subtypes. The use of overexpression and knockdown technologies confirmed the roles of LSR and CD44 in regulating iota toxin endocytosis and induction of cell death. Lastly, cytotoxicity assays were used to demonstrate the effect of iota toxin on a validated set of tamoxifen resistant breast cancer cell lines.

Results

Treatment of 14 breast cancer cell lines revealed that LSR+/CD44- lines were highly sensitive, LSR+/CD44+ lines were slightly sensitive, and LSR-/CD44+ lines were resistant to iota cytotoxicity. Reduction in LSR expression resulted in a significant decrease in toxin sensitivity; however, overexpression of CD44 conveyed toxin resistance. CD44 overexpression was correlated with decreased toxin-stimulated lysosome formation and decreased cytosolic levels of iota toxin. These findings indicated that expression of CD44 drives iota toxin resistance through inhibition of endocytosis in breast cancer cells, a role not previously defined for CD44. Moreover, tamoxifen-resistant breast cancer cells exhibited robust expression of LSR and were highly sensitive to iota-induced cytotoxicity.

Conclusions

Collectively, these data are the first to show that iota toxin has the potential to be an effective, targeted therapy for breast cancer.
Appendix
Available only for authorised users
Literature
1.
Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML, Perou CM: The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007, 13: 2329-2334.CrossRefPubMed
2.
Perou CM, Parker JS, Prat A, Ellis MJ, Bernard PS: Clinical implementation of the intrinsic subtypes of breast cancer. Lancet Oncol. 2010, 11: 718-719. author reply 720–711,CrossRefPubMed
3.
Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, He X, Perou CM: Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 2010, 12: R68-PubMedCentralCrossRefPubMed
4.
Rouzier R, Pusztai L, Delaloge S, Gonzalez-Angulo AM, Andre F, Hess KR, Buzdar AU, Garbay JR, Spielmann M, Mathieu MC, Symmans WF, Wagner P, Atallah D, Valero V, Berry DA, Hortobagyi GN: Nomograms to predict pathologic complete response and metastasis-free survival after preoperative chemotherapy for breast cancer. J Clin Oncol. 2005, 23: 8331-8339.CrossRefPubMed
5.
Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lonning PE, Borresen-Dale AL: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001, 98: 10869-10874.PubMedCentralCrossRefPubMed
6.
Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lonning PE, Brown PO, Borresen-Dale AL, Botstein D: Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A. 2003, 100: 8418-8423.PubMedCentralCrossRefPubMed
7.
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: 1368-1376.CrossRefPubMed
8.
Rakha EA, Elsheikh SE, Aleskandarany MA, Habashi HO, Green AR, Powe DG, El-Sayed ME, Benhasouna A, Brunet JS, Akslen LA, Evans AJ, Blamey R, Reis-Filho JS, Foulkes WD, Ellis IO: Triple-negative breast cancer: distinguishing between basal and nonbasal subtypes. Clin Cancer Res. 2009, 15: 2302-2310.CrossRefPubMed
9.
10.
Allred DC, Brown P, Medina D: The origins of estrogen receptor alpha-positive and estrogen receptor alpha-negative human breast cancer. Breast Cancer Res. 2004, 6: 240-245.PubMedCentralCrossRefPubMed
11.
Dunnwald LK, Rossing MA, Li CI: Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res. 2007, 9: R6-PubMedCentralCrossRefPubMed
12.
Ponta H, Sherman L, Herrlich PA: CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol. 2003, 4: 33-45.CrossRefPubMed
13.
Herbsleb M, Birkenkamp-Demtroder K, Thykjaer T, Wiuf C, Hein AM, Orntoft TF, Dyrskjot L: Increased cell motility and invasion upon knockdown of lipolysis stimulated lipoprotein receptor (LSR) in SW780 bladder cancer cells. BMC Med Genomics. 2008, 1: 31-PubMedCentralCrossRefPubMed
14.
Leth-Larsen R, Terp MG, Christensen AG, Elias D, Kuhlwein T, Jensen ON, Petersen OW, Ditzel HJ: Functional heterogeneity within the CD44 high human breast cancer stem cell-like compartment reveals a gene signature predictive of distant metastasis. Mol Med. 2012, 18: 1109-1121.PubMedCentralCrossRefPubMed
15.
Meyer MJ, Fleming JM, Lin AF, Hussnain SA, Ginsburg E, Vonderhaar BK: CD44posCD49fhiCD133/2hi defines xenograft-initiating cells in estrogen receptor-negative breast cancer. Cancer Res. 2010, 70: 4624-4633.PubMedCentralCrossRefPubMed
16.
Zoller M: CD44: can a cancer-initiating cell profit from an abundantly expressed molecule?. Nat Rev Cancer. 2011, 11: 254-267.CrossRefPubMed
17.
Ricardo S, Vieira AF, Gerhard R, Leitao D, Pinto R, Cameselle-Teijeiro JF, Milanezi F, Schmitt F, Paredes J: Breast cancer stem cell markers CD44, CD24 and ALDH1: expression distribution within intrinsic molecular subtype. J Clin Pathol. 2011, 64: 937-946.CrossRefPubMed
18.
Stratford AL, Reipas K, Maxwell C, Dunn SE: Targeting tumour-initiating cells to improve the cure rates for triple-negative breast cancer. Expert Rev Mol Med. 2010, 12: e22-CrossRefPubMed
19.
Giatromanolaki A, Sivridis E, Fiska A, Koukourakis MI: The CD44+/CD24- phenotype relates to ‘triple-negative’ state and unfavorable prognosis in breast cancer patients. Med Oncol. 2011, 28: 745-752.CrossRefPubMed
20.
Tiezzi DG, Valejo FA, Marana HR, Carrara HH, Benevides L, Antonio HM, Sicchieri RD, Milanezi CM, Silva JS, de Andrade JM: CD44(+)/CD24 (−) cells and lymph node metastasis in stage I and II invasive ductal carcinoma of the breast. Med Oncol. 2012, 29: 1479-1485.CrossRefPubMed
21.
Reaves DK, Fagan-Solis KD, Dunphy K, Oliver SD, Scott DW, Fleming JM: The role of lipolysis stimulated lipoprotein receptor in breast cancer and directing breast cancer cell behavior. PLoS ONE. 2014, 9: e91747-PubMedCentralCrossRefPubMed
22.
Walther W, Petkov S, Kuvardina ON, Aumann J, Kobelt D, Fichtner I, Lemm M, Piontek J, Blasig IE, Stein U, Schlag PM: Novel Clostridium perfringens enterotoxin suicide gene therapy for selective treatment of claudin-3- and −4-overexpressing tumors. Gene Ther. 2012, 19: 494-503.CrossRefPubMed
23.
Shrestha A, McClane BA: Human claudin-8 and −14 are receptors capable of conveying the cytotoxic effects of Clostridium perfringens enterotoxin. MBio. 2013, 4: E00594-12.PubMedCentralPubMed
24.
Michl P, Gress TM: Bacteria and bacterial toxins as therapeutic agents for solid tumors. Curr Cancer Drug Targets. 2004, 4: 689-702.CrossRefPubMed
25.
Lee EJ, Jameson JL: Cell-specific Cre-mediated activation of the diphtheria toxin gene in pituitary tumor cells: potential for cytotoxic gene therapy. Hum Gene Ther. 2002, 13: 533-542.CrossRefPubMed
26.
Zheng JY, Chen D, Chan J, Yu D, Ko E, Pang S: Regression of prostate cancer xenografts by a lentiviral vector specifically expressing diphtheria toxin A. Cancer Gene Ther. 2003, 10: 764-770.CrossRefPubMed
27.
Candolfi M, Xiong W, Yagiz K, Liu C, Muhammad AK, Puntel M, Foulad D, Zadmehr A, Ahlzadeh GE, Kroeger KM, Tesarfreund M, Lee S, Debinski W, Sareen D, Svendsen CN, Rodriguez R, Lowenstein PR, Castro MG: Gene therapy-mediated delivery of targeted cytotoxins for glioma therapeutics. Proc Natl Acad Sci U S A. 2010, 107: 20021-20026.PubMedCentralCrossRefPubMed
28.
Laske DW, Youle RJ, Oldfield EH: Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors. Nat Med. 1997, 3: 1362-1368.CrossRefPubMed
29.
Husain SR, Puri RK: Interleukin-13 receptor-directed cytotoxin for malignant glioma therapy: from bench to bedside. J Neurooncol. 2003, 65: 37-48.CrossRefPubMed
30.
Ayesh B, Matouk I, Ohana P, Sughayer MA, Birman T, Ayesh S, Schneider T, de Groot N, Hochberg A: Inhibition of tumor growth by DT-A expressed under the control of IGF2 P3 and P4 promoter sequences. Mol Ther. 2003, 7: 535-541.CrossRefPubMed
31.
Simpson LL, Stiles BG, Zepeda HH, Wilkins TD: Molecular basis for the pathological actions of Clostridium perfringens iota toxin. Infect Immun. 1987, 55: 118-122.PubMedCentralPubMed
32.
Barth H, Stiles BG: Binary actin-ADP-ribosylating toxins and their use as molecular Trojan horses for drug delivery into eukaryotic cells. Curr Med Chem. 2008, 15: 459-469.CrossRefPubMed
33.
Vandekerckhove J, Schering B, Barmann M, Aktories K: Clostridium perfringens iota toxin ADP-ribosylates skeletal muscle actin in Arg-177. FEBS Lett. 1987, 225: 48-52.CrossRefPubMed
34.
Hilger H, Pust S, von Figura G, Kaiser E, Stiles BG, Popoff MR, Barth H: The long-lived nature of clostridium perfringens iota toxin in mammalian cells induces delayed apoptosis. Infect Immun. 2009, 77: 5593-5601.PubMedCentralCrossRefPubMed
35.
Papatheodorou P, Carette JE, Bell GW, Schwan C, Guttenberg G, Brummelkamp TR, Aktories K: Lipolysis-stimulated lipoprotein receptor (LSR) is the host receptor for the binary toxin Clostridium difficile transferase (CDT). Proc Natl Acad Sci U S A. 2011, 108: 16422-16427.PubMedCentralCrossRefPubMed
36.
Wigelsworth DJ, Ruthel G, Schnell L, Herrlich P, Blonder J, Veenstra TD, Carman RJ, Wilkins TD, Van Nhieu GT, Pauillac S, Gibert M, Sauvonnet N, Stiles BG, Popoff MR, Barth H: CD44 promotes intoxication by the clostridial iota-family toxins. PLoS ONE. 2012, 7: e51356-PubMedCentralCrossRefPubMed
37.
Mann CJ, Khallou J, Chevreuil O, Troussard AA, Guermani LM, Launay K, Delplanque B, Yen FT, Bihain BE: Mechanism of activation and functional significance of the lipolysis-stimulated receptor. Evidence for a role as chylomicron remnant receptor. Biochemistry. 1995, 34: 10421-10431.CrossRefPubMed
38.
Yen FT, Mann CJ, Guermani LM, Hannouche NF, Hubert N, Hornick CA, Bordeau VN, Agnani G, Bihain BE: Identification of a lipolysis-stimulated receptor that is distinct from the LDL receptor and the LDL receptor-related protein. Biochemistry. 1994, 33: 1172-1180.CrossRefPubMed
39.
Yen FT, Masson M, Clossais-Besnard N, Andre P, Grosset JM, Bougueleret L, Dumas JB, Guerassimenko O, Bihain BE: Molecular cloning of a lipolysis-stimulated remnant receptor expressed in the liver. J Biol Chem. 1999, 274: 13390-13398.CrossRefPubMed
40.
Bennett KL, Modrell B, Greenfield B, Bartolazzi A, Stamenkovic I, Peach R, Jackson DG, Spring F, Aruffo A: Regulation of CD44 binding to hyaluronan by glycosylation of variably spliced exons. J Cell Biol. 1995, 131: 1623-1633.CrossRefPubMed
41.
Bartolazzi A, Nocks A, Aruffo A, Spring F, Stamenkovic I: Glycosylation of CD44 is implicated in CD44-mediated cell adhesion to hyaluronan. J Cell Biol. 1996, 132: 1199-1208.CrossRefPubMed
42.
Skelton TP, Zeng C, Nocks A, Stamenkovic I: Glycosylation provides both stimulatory and inhibitory effects on cell surface and soluble CD44 binding to hyaluronan. J Cell Biol. 1998, 140: 431-446.PubMedCentralCrossRefPubMed
43.
Zhao H, Liang Y, Xu Z, Wang L, Zhou F, Li Z, Jin J, Yang Y, Fang Z, Hu Y, Zhang L, Su J, Zha X: N-glycosylation affects the adhesive function of E-Cadherin through modifying the composition of adherens junctions (AJs) in human breast carcinoma cell line MDA-MB-435. J Cell Biochem. 2008, 104: 162-175.CrossRefPubMed
44.
Liwosz A, Lei T, Kukuruzinska MA: N-glycosylation affects the molecular organization and stability of E-cadherin junctions. J Biol Chem. 2006, 281: 23138-23149.CrossRefPubMed
45.
Olsson E, Honeth G, Bendahl PO, Saal LH, Gruvberger-Saal S, Ringner M, Vallon-Christersson J, Jonsson G, Holm K, Lovgren K, Ferno M, Grabau D, Borg A, Hegardt C: CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers. BMC Cancer. 2011, 11: 418-PubMedCentralCrossRefPubMed
46.
Higashi T, Tokuda S, Kitajiri S, Masuda S, Nakamura H, Oda Y, Furuse M: Analysis of the ‘angulin’ proteins LSR, ILDR1 and ILDR2–tricellulin recruitment, epithelial barrier function and implication in deafness pathogenesis. J Cell Sci. 2013, 126: 966-977.CrossRefPubMed
47.
Ponta H, Sleeman J, Dall P, Moll J, Sherman L, Herrlich P: CD44 isoforms in metastatic cancer. Invasion Metastasis. 1994, 14: 82-86.PubMed
48.
O’Driscoll L, Clynes M: Biomarkers and multiple drug resistance in breast cancer. Curr Cancer Drug Targets. 2006, 6: 365-384.CrossRefPubMed
49.
Musgrove EA, Sutherland RL: Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer. 2009, 9: 631-643.CrossRefPubMed
50.
Clarke R, Liu MC, Bouker KB, Gu Z, Lee RY, Zhu Y, Skaar TC, Gomez B, O’Brien K, Wang Y, Hilakivi-Clarke LA: Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling. Oncogene. 2003, 22: 7316-7339.CrossRefPubMed
51.
, : Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005, 365: 1687-1717.CrossRef
52.
Thankamony SP, Knudson W: Acylation of CD44 and its association with lipid rafts are required for receptor and hyaluronan endocytosis. J Biol Chem. 2006, 281: 34601-34609.PubMedCentralCrossRefPubMed
53.
Dubois F, Vandermoere F, Gernez A, Murphy J, Toth R, Chen S, Geraghty KM, Morrice NA, MacKintosh C: Differential 14-3-3 affinity capture reveals new downstream targets of phosphatidylinositol 3-kinase signaling. Mol Cell Proteomics. 2009, 8: 2487-2499.PubMedCentralCrossRefPubMed
54.
Gibert M, Monier MN, Ruez R, Hale ML, Stiles BG, Benmerah A, Johannes L, Lamaze C, Popoff MR: Endocytosis and toxicity of clostridial binary toxins depend on a clathrin-independent pathway regulated by Rho-GDI. Cell Microbiol. 2011, 13: 154-170.CrossRefPubMed
55.
Palaniyandi K, Pockaj BA, Gendler SJ, Chang XB: Human breast cancer stem cells have significantly higher rate of clathrin-independent and caveolin-independent endocytosis than the differentiated breast cancer cells. J Cancer Sci Ther. 2012, 4: 214-222.PubMedCentralCrossRefPubMed
56.
Nagahama M, Umezaki M, Tashiro R, Oda M, Kobayashi K, Shibutani M, Takagishi T, Ishidoh K, Fukuda M, Sakurai J: Intracellular trafficking of Clostridium perfringens iota-toxin b. Infect Immun. 2012, 80: 3410-3416.PubMedCentralCrossRefPubMed
57.
Richard JF, Mainguy G, Gibert M, Marvaud JC, Stiles BG, Popoff MR: Transcytosis of iota-toxin across polarized CaCo-2 cells. Mol Microbiol. 2002, 43: 907-917.CrossRefPubMed
58.
Tilghman SL, Townley I, Zhong Q, Carriere PP, Zou J, Llopis SD, Preyan LC, Williams CC, Skripnikova E, Bratton MR, Zhang Q, Wang G: Proteomic signatures of acquired letrozole resistance in breast cancer: suppressed estrogen signaling and increased cell motility and invasiveness. Mol Cell Proteomics. 2013, 12: 2440-2455.PubMedCentralCrossRefPubMed
59.
Hanamura T, Niwa T, Nishikawa S, Konno H, Gohno T, Tazawa C, Kobayashi Y, Kurosumi M, Takei H, Yamaguchi Y, Ito K, Hayashi S: Androgen metabolite-dependent growth of hormone receptor-positive breast cancer as a possible aromatase inhibitor-resistance mechanism. Breast Cancer Res Treat. 2013, 139: 731-740.CrossRefPubMed
60.
Wong C, Chen S: The development, application and limitations of breast cancer cell lines to study tamoxifen and aromatase inhibitor resistance. J Steroid Biochem Mol Biol. 2012, 131: 83-92.PubMedCentralCrossRefPubMed
61.
Chang M: Tamoxifen resistance in breast cancer. Biomol Ther (Seoul). 2012, 20: 256-267.CrossRef
62.
Pastan I, Hassan R, FitzGerald DJ, Kreitman RJ: Immunotoxin treatment of cancer. Annu Rev Med. 2007, 58: 221-237.CrossRefPubMed
63.
Yang RS, Chang LW, Yang CS, Lin P: Pharmacokinetics and physiologically-based pharmacokinetic modeling of nanoparticles. J Nanosci Nanotechnol. 2010, 10: 8482-8490.CrossRefPubMed
64.
Azemar M, Djahansouzi S, Jager E, Solbach C, Schmidt M, Maurer AB, Mross K, Unger C, von Minckwitz G, Dall P, Groner B, Wels WS: Regression of cutaneous tumor lesions in patients intratumorally injected with a recombinant single-chain antibody-toxin targeted to ErbB2/HER2. Breast Cancer Res Treat. 2003, 82: 155-164.CrossRefPubMed
65.
von Minckwitz G, Harder S, Hovelmann S, Jager E, Al-Batran SE, Loibl S, Atmaca A, Cimpoiasu C, Neumann A, Abera A, Knuth A, Kaufmann M, Jager D, Maurer AB, Wels WS: Phase I clinical study of the recombinant antibody toxin scFv(FRP5)-ETA specific for the ErbB2/HER2 receptor in patients with advanced solid malignomas. Breast Cancer Res. 2005, 7: R617-R626.PubMedCentralCrossRefPubMed
66.
Kreitman RJ, Hassan R, Fitzgerald DJ, Pastan I: Phase I trial of continuous infusion anti-mesothelin recombinant immunotoxin SS1P. Clin Cancer Res. 2009, 15: 5274-5279.PubMedCentralCrossRefPubMed
67.
Marvaud JC, Smith T, Hale ML, Popoff MR, Smith LA, Stiles BG: Clostridium perfringens iota-toxin: mapping of receptor binding and Ia docking domains on Ib. Infect Immun. 2001, 69: 2435-2441.PubMedCentralCrossRefPubMed
68.
Sakurai J, Kobayashi K: Lethal and dermonecrotic activities of Clostridium perfringens lota toxin: biological activities induced by cooperation of two nonlinked components. Microbiol Immunol. 1995, 39: 249-253.CrossRefPubMed
69.
70.
Perelle S, Scalzo S, Kochi S, Mock M, Popoff MR: Immunological and functional comparison between Clostridium perfringens iota toxin, C. spiroforme toxin, and anthrax toxins. FEMS Microbiol Lett. 1997, 146: 117-121.CrossRefPubMed
71.
Fleming JM, Ginsburg E, McAndrew CW, Heger CD, Cheston L, Rodriguez-Canales J, Vonderhaar BK, Goldsmith P: Characterization of Δ7/11, a functional prolactin-binding protein. J Mol Endocrinol. 2013, 50: 79-90.CrossRefPubMed
72.
Metadata
Title
Challenging the roles of CD44 and lipolysis stimulated lipoprotein receptor in conveying Clostridium perfringens iota toxin cytotoxicity in breast cancer
Authors
Katerina D Fagan-Solis
Denise K Reaves
M Cristina Rangel
Michel R Popoff
Bradley G Stiles
Jodie M Fleming
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-163

Other articles of this Issue 1/2014

Molecular Cancer 1/2014 Go to the issue

Research

Identification and characterization of Dicer1e, a Dicer1 protein variant, in oral cancer cells

Research

miR-193a-3p regulates the multi-drug resistance of bladder cancer by targeting the LOXL4 gene and the Oxidative Stress pathway

Research

CUL4A overexpression enhances lung tumor growth and sensitizes lung cancer cells to Erlotinib via transcriptional regulation of EGFR

Research

mTOR inhibition and levels of the DNA repair protein MGMT in T98G glioblastoma cells

Review

Targeting of erbB3 receptor to overcome resistance in cancer treatment

Research

Thymoquinone-induced conformational changes of PAK1 interrupt prosurvival MEK-ERK signaling in colorectal cancer
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