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
BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Chemotherapy-induced hyaluronan production: a novel chemoresistance mechanism in ovarian cancer

Authors: Carmela Ricciardelli, Miranda P Ween, Noor A Lokman, Izza A Tan, Carmen E Pyragius, Martin K Oehler

Published in: BMC Cancer | Issue 1/2013

Login to get access

Abstract

Background

Hyaluronan (HA) an important component of the extracellular matrix, has been linked to tumor progression and drug resistance in several malignancies. However, limited data is available for ovarian cancer. This study investigated the role of hyaluronan (HA) and a potential link between the HA-CD44 pathway and membrane ATP binding cassette (ABC) transporter proteins in ovarian cancer chemoresistance.

Methods

We investigated the ability of HA to block the cytotoxic effects of the chemotherapy drug carboplatin, and to regulate the expression of ABC transporters in ovarian cancer cells. We also examined HA serum levels in ovarian cancer patients prior to and following chemotherapy and assessed its prognostic relevance.

Results

HA increased the survival of carboplatin treated ovarian cancer cells expressing the HA receptor, CD44 (OVCAR-5 and OV-90). Carboplatin significantly increased expression of HAS2, HAS3 and ABCC2 and HA secretion in ovarian cancer cell conditioned media. Serum HA levels were significantly increased in patients following platinum based chemotherapy and at both 1st and 2nd recurrence when compared with HA levels prior to treatment. High serum HA levels (>50 μg/ml) prior to chemotherapy treatment were associated with significantly reduced progression-free (P = 0.014) and overall survival (P = 0.036). HA production in ovarian cancer cells was increased in cancer tissues collected following chemotherapy treatment and at recurrence. Furthermore HA treatment significantly increased the expression of ABC drug transporters (ABCB3, ABCC1, ABCC2, and ABCC3), but only in ovarian cancer cells expressing CD44. The effects of HA and carboplatin on ABC transporter expression in ovarian cancer cells could be abrogated by HA oligomer treatment. Importantly, HA oligomers increased the sensitivity of chemoresistant SKOV3 cells to carboplatin.

Conclusions

Our findings indicate that carboplatin chemotherapy induces HA production which can contribute to chemoresistance by regulating ABC transporter expression. The HA-CD44 signaling pathway is therefore a promising target in platinum resistant ovarian cancer.
Appendix
Available only for authorised users
Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61 (2): 69-90. 10.3322/caac.20107.CrossRefPubMed
2.
Agarwal R, Kaye SB: Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer. 2003, 3 (7): 502-516. 10.1038/nrc1123.CrossRefPubMed
3.
Dassa E, Schneider E: The rise of a protein family: ATP-binding cassette systems. Res Microbiol. 2001, 152 (3–4): 203-CrossRefPubMed
4.
Dean M, Allikmets R: Complete characterization of the human ABC gene family. J Bioenerg Biomembr. 2001, 33 (6): 475-479. 10.1023/A:1012823120935.CrossRefPubMed
5.
Lewis VG, Ween MP, McDevitt CA: The role of ATP-binding cassette transporters in bacterial pathogenicity. Protoplasma. 2012, 249 (4): 919-942. 10.1007/s00709-011-0360-8.CrossRefPubMed
6.
Kartner N, Shales M, Riordan JR, Ling V: Daunorubicin-resistant Chinese hamster ovary cells expressing multidrug resistance and a cell-surface P-glycoprotein. Cancer Res. 1983, 43 (9): 4413-4419.PubMed
7.
Fojo AT, Ueda K, Slamon DJ, Poplack DG, Gottesman MM, Pastan I: Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci U S A. 1987, 84 (1): 265-269. 10.1073/pnas.84.1.265.CrossRefPubMedPubMedCentral
8.
Kamazawa S, Kigawa J, Kanamori Y, Itamochi H, Sato S, Iba T, Terakawa N: Multidrug resistance gene-1 is a useful predictor of Paclitaxel-based chemotherapy for patients with ovarian cancer. Gynecol Oncol. 2002, 86 (2): 171-176. 10.1006/gyno.2002.6738.CrossRefPubMed
9.
Duan Z, Brakora KA, Seiden MV: Inhibition of ABCB1 (MDR1) and ABCB4 (MDR3) expression by small interfering RNA and reversal of paclitaxel resistance in human ovarian cancer cells. Mol Cancer Ther. 2004, 3 (7): 833-838.PubMed
10.
Yakirevich E, Sabo E, Naroditsky I, Sova Y, Lavie O, Resnick MB: Multidrug resistance-related phenotype and apoptosis-related protein expression in ovarian serous carcinomas. Gynecol Oncol. 2006, 100 (1): 152-159. 10.1016/j.ygyno.2005.08.050.CrossRefPubMed
11.
Sandusky GE, Mintze KS, Pratt SE, Dantzig AH: Expression of multidrug resistance-associated protein 2 (MRP2) in normal human tissues and carcinomas using tissue microarrays. Histopathology. 2002, 41 (1): 65-74. 10.1046/j.1365-2559.2002.01403.x.CrossRefPubMed
12.
Ohishi Y, Oda Y, Uchiumi T, Kobayashi H, Hirakawa T, Miyamoto S, Kinukawa N, Nakano H, Kuwano M, Tsuneyoshi M: ATP-binding cassette superfamily transporter gene expression in human primary ovarian carcinoma. Clin Cancer Res. 2002, 8 (12): 3767-3775.PubMed
13.
Surowiak P, Materna V, Kaplenko I, Spaczynski M, Dolinska-Krajewska B, Gebarowska E, Dietel M, Zabel M, Lage H: ABCC2 (MRP2, cMOAT) can be localized in the nuclear membrane of ovarian carcinomas and correlates with resistance to cisplatin and clinical outcome. Clin Cancer Res. 2006, 12 (23): 7149-7158. 10.1158/1078-0432.CCR-06-0564.CrossRefPubMed
14.
Faggad A, Darb-Esfahani S, Wirtz R, Sinn B, Sehouli J, Konsgen D, Lage H, Noske A, Weichert W, Buckendahl AC, et al: Expression of multidrug resistance-associated protein 1 in invasive ovarian carcinoma: implication for prognosis. Histopathology. 2009, 54 (6): 657-666. 10.1111/j.1365-2559.2009.03297.x.CrossRefPubMed
15.
Auner V, Sehouli J, Oskay-Oezcelik G, Horvat R, Speiser P, Zeillinger R: ABC transporter gene expression in benign and malignant ovarian tissue. Gynecol Oncol. 2010, 117 (2): 198-201. 10.1016/j.ygyno.2009.10.077.CrossRefPubMed
16.
Toole BP, Slomiany MG: Hyaluronan, CD44 and Emmprin: partners in cancer cell chemoresistance. Drug Resist Updat. 2008, 11 (3): 110-121. 10.1016/j.drup.2008.04.002.CrossRefPubMedPubMedCentral
17.
Toole BP: Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer. 2004, 4 (7): 528-539. 10.1038/nrc1391.CrossRefPubMed
18.
19.
Anttila MA, Tammi RH, Tammi MI, Syrjanen KJ, Saarikoski SV, Kosma VM: High levels of stromal hyaluronan predict poor disease outcome in epithelial ovarian cancer. Cancer Res. 2000, 60 (1): 150-155.PubMed
20.
Hiltunen EL, Anttila M, Kultti A, Ropponen K, Penttinen J, Yliskoski M, Kuronen AT, Juhola M, Tammi R, Tammi M, et al: Elevated hyaluronan concentration without hyaluronidase activation in malignant epithelial ovarian tumors. Cancer Res. 2002, 62 (22): 6410-6413.PubMed
21.
Jojovic M, Delpech B, Prehm P, Schumacher U: Expression of hyaluronate and hyaluronate synthase in human primary tumours and their metastases in scid mice. Cancer Lett. 2002, 188 (1–2): 181-189.CrossRefPubMed
22.
Yeo TK, Nagy JA, Yeo KT, Dvorak HF, Toole BP: Increased hyaluronan at sites of attachment to mesentery by CD44-positive mouse ovarian and breast tumor cells. Am J Pathol. 1996, 148 (6): 1733-1740.PubMedPubMedCentral
23.
Catterall JB, Jones LM, Turner GA: Membrane protein glycosylation and CD44 content in the adhesion of human ovarian cancer cells to hyaluronan. Clin Exp Metastasis. 1999, 17 (7): 583-591. 10.1023/A:1006756518500.CrossRefPubMed
24.
Casey RC, Skubitz AP: CD44 and beta1 integrins mediate ovarian carcinoma cell migration toward extracellular matrix proteins. Clin Exp Metastasis. 2000, 18 (1): 67-75. 10.1023/A:1026519016213.CrossRefPubMed
25.
Ween MP, Hummitzsch K, Rodgers RJ, Oehler MK, Ricciardelli C: Versican induces a pro-metastatic ovarian cancer cell behavior which can be inhibited by small hyaluronan oligosaccharides. Clin Exp Metastasis. 2011, 28 (2): 113-125. 10.1007/s10585-010-9363-7.CrossRefPubMed
26.
Vincent T, Molina L, Espert L, Mechti N: Hyaluronan, a major non-protein glycosaminoglycan component of the extracellular matrix in human bone marrow, mediates dexamethasone resistance in multiple myeloma. Br J Haematol. 2003, 121 (2): 259-269. 10.1046/j.1365-2141.2003.04282.x.CrossRefPubMed
27.
Wang SJ, Bourguignon LY: Hyaluronan and the interaction between CD44 and epidermal growth factor receptor in oncogenic signaling and chemotherapy resistance in head and neck cancer. Arch Otolaryngol Head Neck Surg. 2006, 132 (7): 771-778. 10.1001/archotol.132.7.771.CrossRefPubMed
28.
Bourguignon LY, Peyrollier K, Xia W, Gilad E: Hyaluronan-CD44 interaction activates stem cell marker Nanog, Stat-3-mediated MDR1 gene expression, and ankyrin-regulated multidrug efflux in breast and ovarian tumor cells. J Biol Chem. 2008, 283 (25): 17635-17651. 10.1074/jbc.M800109200.CrossRefPubMedPubMedCentral
29.
Torre C, Wang SJ, Xia W, Bourguignon LY: Reduction of hyaluronan-CD44-mediated growth, migration, and cisplatin resistance in head and neck cancer due to inhibition of Rho kinase and PI-3 kinase signaling. Arch Otolaryngol Head Neck Surg. 2010, 136 (5): 493-501. 10.1001/archoto.2010.25.CrossRefPubMedPubMedCentral
30.
Misra S, Ghatak S, Toole BP: Regulation of MDR1 expression and drug resistance by a positive feedback loop involving hyaluronan, phosphoinositide 3-kinase, and ErbB2. J Biol Chem. 2005, 280 (21): 20310-20315. 10.1074/jbc.M500737200.CrossRefPubMed
31.
Bourguignon LY, Xia W, Wong G: Hyaluronan-mediated CD44 interaction with p300 and SIRT1 regulates beta-catenin signaling and NFkappaB-specific transcription activity leading to MDR1 and Bcl-xL gene expression and chemoresistance in breast tumor cells. J Biol Chem. 2009, 284 (5): 2657-2671.CrossRefPubMedPubMedCentral
32.
Cordo Russo RI, Garcia MG, Alaniz L, Blanco G, Alvarez E, Hajos SE: Hyaluronan oligosaccharides sensitize lymphoma resistant cell lines to vincristine by modulating P-glycoprotein activity and PI3K/Akt pathway. Int J Cancer. 2008, 122 (5): 1012-1018.CrossRefPubMed
33.
Ohashi R, Takahashi F, Cui R, Yoshioka M, Gu T, Sasaki S, Tominaga S, Nishio K, Tanabe KK, Takahashi K: Interaction between CD44 and hyaluronate induces chemoresistance in non-small cell lung cancer cell. Cancer Lett. 2007, 252 (2): 225-234. 10.1016/j.canlet.2006.12.025.CrossRefPubMed
34.
Gilg AG, Tye SL, Tolliver LB, Wheeler WG, Visconti RP, Duncan JD, Kostova FV, Bolds LN, Toole BP, Maria BL: Targeting hyaluronan interactions in malignant gliomas and their drug-resistant multipotent progenitors. Clin Cancer Res. 2008, 14 (6): 1804-1813. 10.1158/1078-0432.CCR-07-1228.CrossRefPubMed
35.
Chen H, Hao J, Wang L, Li Y: Coexpression of invasive markers (uPA, CD44) and multiple drug-resistance proteins (MDR1, MRP2) is correlated with epithelial ovarian cancer progression. Br J Cancer. 2009, 101 (3): 432-440. 10.1038/sj.bjc.6605185.CrossRefPubMedPubMedCentral
36.
Johnson SW, Laub PB, Beesley JS, Ozols RF, Hamilton TC: Increased platinum-DNA damage tolerance is associated with cisplatin resistance and cross-resistance to various chemotherapeutic agents in unrelated human ovarian cancer cell lines. Cancer Res. 1997, 57 (5): 850-856.PubMed
37.
Ween MP, Lokman NA, Hoffmann P, Rodgers RJ, Ricciardelli C, Oehler MK: Transforming growth factor-beta-induced protein secreted by peritoneal cells increases the metastatic potential of ovarian cancer cells. Int J Cancer. 2011, 128 (7): 1570-1584. 10.1002/ijc.25494.CrossRefPubMed
38.
Suwiwat S, Ricciardelli C, Tammi R, Tammi M, Auvinen P, Kosma VM, LeBaron RG, Raymond WA, Tilley WD, Horsfall DJ: Expression of extracellular matrix components versican, chondroitin sulfate, tenascin, and hyaluronan, and their association with disease outcome in node-negative breast cancer. Clin Cancer Res. 2004, 10 (7): 2491-2498. 10.1158/1078-0432.CCR-03-0146.CrossRefPubMed
39.
Materna V, Stege A, Surowiak P, Priebsch A, Lage H: RNA interference-triggered reversal of ABCC2-dependent cisplatin resistance in human cancer cells. Biochem Biophys Res Commun. 2006, 348 (1): 153-157. 10.1016/j.bbrc.2006.07.022.CrossRefPubMed
40.
Fletcher JI, Haber M, Henderson MJ, Norris MD: ABC transporters in cancer: more than just drug efflux pumps. Nat Rev Cancer. 2010, 10 (2): 147-156. 10.1038/nrc2789.CrossRefPubMed
41.
Shukla S, Ohnuma S, Ambudkar SV: Improving cancer chemotherapy with modulators of ABC drug transporters. Curr Drug Targets. 2011, 12 (5): 621-630. 10.2174/138945011795378540.CrossRefPubMedPubMedCentral
42.
Bourguignon LY: Hyaluronan-mediated CD44 activation of RhoGTPase signaling and cytoskeleton function promotes tumor progression. Semin Cancer Biol. 2008, 18 (4): 251-259. 10.1016/j.semcancer.2008.03.007.CrossRefPubMedPubMedCentral
43.
Auvinen P, Tammi R, Parkkinen J, Tammi M, Agren U, Johansson R, Hirvikoski P, Eskelinen M, Kosma VM: Hyaluronan in peritumoral stroma and malignant cells associates with breast cancer spreading and predicts survival. Am J Pathol. 2000, 156 (2): 529-536. 10.1016/S0002-9440(10)64757-8.CrossRefPubMedPubMedCentral
44.
Logan RM, Stringer AM, Bowen JM, Yeoh AS, Gibson RJ, Sonis ST, Keefe DM: The role of pro-inflammatory cytokines in cancer treatment-induced alimentary tract mucositis: pathobiology, animal models and cytotoxic drugs. Cancer Treat Rev. 2007, 33 (5): 448-460. 10.1016/j.ctrv.2007.03.001.CrossRefPubMed
45.
Derin D, Soydinc HO, Guney N, Tas F, Camlica H, Duranyildiz D, Yasasever V, Topuz E: Serum levels of apoptosis biomarkers, survivin and TNF-alpha in nonsmall cell lung cancer. Lung Cancer. 2008, 59 (2): 240-245. 10.1016/j.lungcan.2007.08.005.CrossRefPubMed
46.
Sampson PM, Rochester CL, Freundlich B, Elias JA: Cytokine regulation of human lung fibroblast hyaluronan (hyaluronic acid) production. Evidence for cytokine-regulated hyaluronan (hyaluronic acid) degradation and human lung fibroblast-derived hyaluronidase. J Clin Invest. 1992, 90 (4): 1492-1503. 10.1172/JCI116017.CrossRefPubMedPubMedCentral
47.
Campo GM, Avenoso A, Campo S, Angela D, Ferlazzo AM, Calatroni A: TNF-alpha, IFN-gamma, and IL-1beta modulate hyaluronan synthase expression in human skin fibroblasts: synergistic effect by concomital treatment with FeSO4 plus ascorbate. MCB. 2006, 292 (1–2): 169-178.
48.
Hyc A, Osiecka-Iwan A, Niderla-Bielinska J, Jankowska-Steifer E, Moskalewski S: Pro- and anti-inflammatory cytokines increase hyaluronan production by rat synovial membrane in vitro. Int J Mol Med. 2009, 24 (4): 579-585.PubMed
49.
Vigetti D, Genasetti A, Karousou E, Viola M, Moretto P, Clerici M, Deleonibus S, De Luca G, Hascall VC, Passi A: Proinflammatory cytokines induce hyaluronan synthesis and monocyte adhesion in human endothelial cells through hyaluronan synthase 2 (HAS2) and the nuclear factor-kappaB (NF-kappaB) pathway. J Biol Chem. 2010, 285 (32): 24639-24645. 10.1074/jbc.M110.134536.CrossRefPubMedPubMedCentral
50.
Misra S, Ghatak S, Zoltan-Jones A, Toole BP: Regulation of multidrug resistance in cancer cells by hyaluronan. J Biol Chem. 2003, 278 (28): 25285-25288. 10.1074/jbc.C300173200.CrossRefPubMed
51.
Qin Z, Dai L, Bratoeva M, Slomiany MG, Toole BP, Parsons C: Cooperative roles for emmprin and LYVE-1 in the regulation of chemoresistance for primary effusion lymphoma. Leukemia. 2011, 25 (10): 1598-1609. 10.1038/leu.2011.144.CrossRefPubMedPubMedCentral
52.
Slomiany MG, Dai L, Bomar PA, Knackstedt TJ, Kranc DA, Tolliver L, Maria BL, Toole BP: Abrogating drug resistance in malignant peripheral nerve sheath tumors by disrupting hyaluronan-CD44 interactions with small hyaluronan oligosaccharides. Cancer Res. 2009, 69 (12): 4992-4998. 10.1158/0008-5472.CAN-09-0143.CrossRefPubMedPubMedCentral
53.
Liu CM, Chang CH, Yu CH, Hsu CC, Huang LL: Hyaluronan substratum induces multidrug resistance in human mesenchymal stem cells via CD44 signaling. Cell Tissue Res. 2009, 336 (3): 465-475. 10.1007/s00441-009-0780-3.CrossRefPubMed
54.
Miletti-Gonzalez KE, Chen S, Muthukumaran N, Saglimbeni GN, Wu X, Yang J, Apolito K, Shih WJ, Hait WN, Rodriguez-Rodriguez L: The CD44 receptor interacts with P-glycoprotein to promote cell migration and invasion in cancer. Cancer Res. 2005, 65 (15): 6660-6667. 10.1158/0008-5472.CAN-04-3478.CrossRefPubMed
55.
Hooijberg JH, Broxterman HJ, Kool M, Assaraf YG, Peters GJ, Noordhuis P, Scheper RJ, Borst P, Pinedo HM, Jansen G: Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2. Cancer Res. 1999, 59 (11): 2532-2535.PubMed
56.
Kigawa J, Minagawa Y, Cheng X, Terakawa N: Gamma-glutamyl cysteine synthetase up-regulates glutathione and multidrug resistance-associated protein in patients with chemoresistant epithelial ovarian cancer. Clin Cancer Res. 1998, 4 (7): 1737-1741.PubMed
57.
Beretta GL, Benedetti V, Cossa G, Assaraf YG, Bram E, Gatti L, Corna E, Carenini N, Colangelo D, Howell SB, et al: Increased levels and defective glycosylation of MRPs in ovarian carcinoma cells resistant to oxaliplatin. Biochem Pharmacol. 2010, 79 (8): 1108-1117. 10.1016/j.bcp.2009.12.002.CrossRefPubMed
58.
Ma JJ, Chen BL, Xin XY: Inhibition of multi-drug resistance of ovarian carcinoma by small interfering RNA targeting to MRP2 gene. Arch Gynecol Obstet. 2009, 279 (2): 149-157. 10.1007/s00404-008-0690-8.CrossRefPubMed
59.
Auzenne E, Ghosh SC, Khodadadian M, Rivera B, Farquhar D, Price RE, Ravoori M, Kundra V, Freedman RS, Klostergaard J: Hyaluronic acid-paclitaxel: antitumor efficacy against CD44(+) human ovarian carcinoma xenografts. Neoplasia. 2007, 9 (6): 479-486. 10.1593/neo.07229.CrossRefPubMedPubMedCentral
60.
Banzato A, Bobisse S, Rondina M, Renier D, Bettella F, Esposito G, Quintieri L, Melendez-Alafort L, Mazzi U, Zanovello P, et al: A paclitaxel-hyaluronan bioconjugate targeting ovarian cancer affords a potent in vivo therapeutic activity. Clin Cancer Res. 2008, 14 (11): 3598-3606. 10.1158/1078-0432.CCR-07-2019.CrossRefPubMed
61.
Lee SJ, Ghosh SC, Han HD, Stone RL, Bottsford-Miller J, Shen DY, Auzenne E, Lopez-Araujo A, Lu C, Lee SJ, Ghosh SC, Han HD, Stone RL, Bottsford-Miller J, Shen DY, Auzenne E, Lopez-Araujo A, Lu C, Nishimura M, et al: Metronomic Activity of CD44-Targeted Hyaluronic Acid-Paclitaxel in Ovarian Carcinoma. Clin Cancer Res. 2012, 18 (15): 4114-4121. 10.1158/1078-0432.CCR-11-3250.CrossRefPubMedPubMedCentral
62.
Provenzano PP, Cuevas C, Chang AE, Goel VK, Von Hoff DD, Hingorani SR: Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell. 2012, 21 (3): 418-429. 10.1016/j.ccr.2012.01.007.CrossRefPubMedPubMedCentral
63.
Jacobetz MA, Chan DS, Neesse A, Bapiro TE, Cook N, Frese KK, Feig C, Nakagawa T, Caldwell ME, Zecchini HI, et al: Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut. 2012, 62 (1): 112-120.CrossRefPubMedPubMedCentral
Metadata
Title
Chemotherapy-induced hyaluronan production: a novel chemoresistance mechanism in ovarian cancer
Authors
Carmela Ricciardelli
Miranda P Ween
Noor A Lokman
Izza A Tan
Carmen E Pyragius
Martin K Oehler
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-476

Other articles of this Issue 1/2013

BMC Cancer 1/2013 Go to the issue

Research article

Epigenetic regulation of L1CAM in endometrial carcinoma: comparison to cancer–testis (CT-X) antigens

Research article

Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma

Research article

Reduced mrna expression level of corticotropin-releasing hormone-binding protein is associated with aggressive human kidney cancer

Research article

Evaluation of a curcumin analog as an anti-cancer agent inducing ER stress-mediated apoptosis in non-small cell lung cancer cells

Research article

Older renal cell cancer patients experience increased rates of venous thromboembolic events: a retrospective cohort study of SEER-Medicare data

Research article

Cancer odor in the blood of ovarian cancer patients: a retrospective study of detection by dogs during treatment, 3 and 6 months afterward
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