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
Tumor Biology
Published in: Tumor Biology 11/2014

01-11-2014 | Research Article

CCAR2 deficiency augments genotoxic stress-induced apoptosis in the presence of melatonin in non-small cell lung cancer cells

Authors: Wootae Kim, Joo-Won Jeong, Ja-Eun Kim

Published in: Tumor Biology | Issue 11/2014

Login to get access

Abstract

Melatonin exhibits oncostatic activity in several cancers but does not lead to cytotoxicity in estrogen receptor (ER)-negative non-small cell lung cancers (NSCLCs). In an effort to overcome the melatonin resistance of these cancers, we investigated whether cell cycle and apoptosis regulator 2 (CCAR2) depletion would promote apoptosis following genotoxic stress in melatonin-resistant cancer cells. Ordinarily, the NSCLC cell lines A549 and A427 did not undergo cell death following melatonin treatment for short period. These cell lines were irradiated with UV, a source of genotoxic damage, to trigger apoptotic signaling. Treatment with melatonin prior to irradiation did not produce any significant change in apoptosis. By contrast, in CCAR2-deficient cells, melatonin treatment increased apoptosis induced by genotoxic stress; this effect was dependent on the dose of melatonin. The increase in apoptosis in CCAR2-deficient cells was not dependent on SIRT1. The results indicate that CCAR2 is critical for maintaining cell survival in the presence of melatonin under genotoxic stress. Furthermore, CCAR2 is overexpressed in NSCLC; therefore, melatonin could be used as a potential supplement to classical anticancer drugs in therapies against CCAR2-deficient cancers.
Literature
1.
Stefulj J, Hortner M, Ghosh M, Schauenstein K, Rinner I, Wolfler A, et al. Gene expression of the key enzymes of melatonin synthesis in extrapineal tissues of the rat. J Pineal Res. 2001;30(4):243–7.PubMedCrossRef
2.
Boutin JA, Audinot V, Ferry G, Delagrange P. Molecular tools to study melatonin pathways and actions. Trends Pharmacol Sci. 2005;26(8):412–9. PubMedCrossRef
3.
Reiter RJ, Tan DX, Manchester LC, Pilar Terron M, Flores LJ, Koppisepi S. Medical implications of melatonin: receptor-mediated and receptor-independent actions. Adv Med Sci. 2007;52:11–28.PubMed
4.
Simonneaux V, Ribelayga C. Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters. Pharmacol Rev. 2003;55(2):325–95.PubMedCrossRef
5.
Petrosillo G, Di Venosa N, Pistolese M, Casanova G, Tiravanti E, Colantuono G, et al. Protective effect of melatonin against mitochondrial dysfunction associated with cardiac ischemia- reperfusion: role of cardiolipin. FASEB J. 2006;20(2):269–76.PubMedCrossRef
6.
Allegra M, Reiter RJ, Tan DX, Gentile C, Tesoriere L, Livrea MA. The chemistry of melatonin’s interaction with reactive species. J Pineal Res. 2003;34(1):1–10.PubMedCrossRef
7.
Reiter RJ, Tan DX, Mayo JC, Sainz RM, Leon J, Czarnocki Z. Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. Acta Biochim Pol. 2003;50(4):1129–46.PubMed
8.
Jung B, Ahmad N. Melatonin in cancer management: progress and promise. Cancer Res. 2006;66(20):9789–93.PubMedCrossRef
9.
Diederich M. Natural compounds as inducers of cell death : volume 1. New York: Springer; 2012.
10.
Bizzarri M, Proietti S, Cucina A, Reiter RJ. Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer: a review. Expert Opin Ther Targets. 2013;17(12):1483–96.PubMedCrossRef
11.
Carbajo-Pescador S, Steinmetz C, Kashyap A, Lorenz S, Mauriz JL, Heise M, et al. Melatonin induces transcriptional regulation of Bim by FoxO3a in HepG2 cells. Br J Cancer. 2013;108(2):442–9.PubMedCentralPubMedCrossRef
12.
Cini G, Neri B, Pacini A, Cesati V, Sassoli C, Quattrone S, et al. Antiproliferative activity of melatonin by transcriptional inhibition of cyclin D1 expression: a molecular basis for melatonin-induced oncostatic effects. J Pineal Res. 2005;39(1):12–20.PubMedCrossRef
13.
Cos S, Fernandez R, Guezmes A, Sanchez-Barcelo EJ. Influence of melatonin on invasive and metastatic properties of MCF-7 human breast cancer cells. Cancer Res. 1998;58(19):4383–90.PubMed
14.
Hill SM, Blask DE. Effects of the pineal hormone melatonin on the proliferation and morphological characteristics of human breast cancer cells (MCF-7) in culture. Cancer Res. 1988;48(21):6121–6.PubMed
15.
Hill SM, Frasch T, Xiang S, Yuan L, Duplessis T, Mao L. Molecular mechanisms of melatonin anticancer effects. Integr Cancer Ther. 2009;8(4):337–46.PubMedCrossRef
16.
Joo SS, Yoo YM. Melatonin induces apoptotic death in LNCaP cells via p38 and JNK pathways: therapeutic implications for prostate cancer. J Pineal Res. 2009;47(1):8–14.PubMedCrossRef
17.
Mao L, Dauchy RT, Blask DE, Slakey LM, Xiang S, Yuan L, et al. Circadian gating of epithelial-to-mesenchymal transition in breast cancer cells via melatonin-regulation of GSK3beta. Mol Endocrinol. 2012;26(11):1808–20. PubMedCentralPubMedCrossRef
18.
Proietti S, Cucina A, Reiter RJ, Bizzarri M. Molecular mechanisms of melatonin’s inhibitory actions on breast cancers. Cell Mol Life Sci. 2013;70(12):2139–57.PubMedCrossRef
19.
Sainz RM, Mayo JC, Tan DX, Leon J, Manchester L, Reiter RJ. Melatonin reduces prostate cancer cell growth leading to neuroendocrine differentiation via a receptor and PKA independent mechanism. Prostate. 2005;63(1):29–43.PubMedCrossRef
20.
Grant SG, Melan MA, Latimer JJ, Witt-Enderby PA. Melatonin and breast cancer: cellular mechanisms, clinical studies and future perspectives. Expert Rev Mol Med. 2009;11:e5.PubMedCrossRef
21.
Sanchez-Barcelo EJ, Cos S, Fernandez R, Mediavilla MD. Melatonin and mammary cancer: a short review. Endocr Relat Cancer. 2003;10(2):153–9.PubMedCrossRef
22.
Sanchez-Barcelo EJ, Cos S, Mediavilla D, Martinez-Campa C, Gonzalez A, Alonso-Gonzalez C. Melatonin-estrogen interactions in breast cancer. J Pineal Res. 2005;38(4):217–22.PubMedCrossRef
23.
Cos S, Gonzalez A, Martinez-Campa C, Mediavilla MD, Alonso-Gonzalez C, Sanchez-Barcelo EJ. Estrogen-signaling pathway: a link between breast cancer and melatonin oncostatic actions. Cancer Detect Prev. 2006;30(2):118–28.PubMedCrossRef
24.
Yuan L, Collins AR, Dai J, Dubocovich ML, Hill SM. MT(1) melatonin receptor overexpression enhances the growth suppressive effect of melatonin in human breast cancer cells. Mol Cell Endocrinol. 2002;192(1–2):147–56.PubMedCrossRef
25.
Hill SM, Spriggs LL, Simon MA, Muraoka H, Blask DE. The growth inhibitory action of melatonin on human breast cancer cells is linked to the estrogen response system. Cancer Lett. 1992;64(3):249–56.PubMedCrossRef
26.
Lissoni P, Ardizzoia A, Barni S, Paolorossi F, Tancini G, Meregalli S, et al. A randomized study of tamoxifen alone versus tamoxifen plus melatonin in estrogen receptor-negative heavily pretreated metastatic breast-cancer patients. Oncol Rep. 1995;2(5):871–3.PubMed
27.
Close P, East P, Dirac-Svejstrup AB, Hartmann H, Heron M, Maslen S, et al. DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation. Nature. 2012;484(7394):386–9.PubMedCentralPubMedCrossRef
28.
Escande C, Chini CCS, Nin V, Dykhouse KM, Novak CM, Levine J, et al. Deleted in breast cancer-1 regulates SIRT1 activity and contributes to high-fat diet-induced liver steatosis in mice. J Clin Invest. 2010;120(2):545–58. PubMedCentralPubMedCrossRef
29.
Fu J, Jiang J, Li J, Wang S, Shi G, Feng Q, et al. Deleted in breast cancer 1, a novel androgen receptor (AR) coactivator that promotes AR DNA-binding activity. J Biol Chem. 2009;284(11):6832–40.PubMedCentralPubMedCrossRef
30.
Koyama S, Wada-Hiraike O, Nakagawa S, Tanikawa M, Hiraike H, Miyamoto Y, et al. Repression of estrogen receptor beta function by putative tumor suppressor DBC1. Biochem Biophys Res Commun. 2010;392(3):357–62.PubMedCrossRef
31.
Chini CC, Escande C, Nin V, Chini EN. Histone deacetylase 3 is negatively regulated by the nuclear protein deleted in breast cancer 1 (DBC1). J Biol Chem. 2010;285(52):40830–7.PubMedCentralPubMedCrossRef
32.
Chini CC, Escande C, Nin V, Chini EN. DBC1 (Deleted in Breast Cancer 1) modulates the stability and function of the nuclear receptor Rev-erbalpha. Biochem J. 2013;451(3):453–61.PubMedCentralPubMedCrossRef
33.
Garapaty S, Xu CF, Trojer P, Mahajan MA, Neubert TA, Samuels HH. Identification and characterization of a novel nuclear protein complex involved in nuclear hormone receptor-mediated gene regulation. J Biol Chem. 2009;284(12):7542–52.PubMedCentralPubMedCrossRef
34.
Hiraike H, Wada-Hiraike O, Nakagawa S, Koyama S, Miyamoto Y, Sone K, et al. Identification of DBC1 as a transcriptional repressor for BRCA1. Br J Cancer. 2010;102(6):1061–7.PubMedCentralPubMedCrossRef
35.
36.
Nin V, Escande C, Chini CC, Giri S, Camacho-Pereira J, Matalonga J, et al. Role of deleted in breast cancer 1 (DBC1) protein in SIRT1 deacetylase activation induced by protein kinase A and AMP-activated protein kinase. J Biol Chem. 2012;287(28):23489–501.PubMedCentralPubMedCrossRef
37.
Sundararajan R, Chen G, Mukherjee C, White E. Caspase-dependent processing activates the proapoptotic activity of deleted in breast cancer-1 during tumor necrosis factor-alpha-mediated death signaling. Oncogene. 2005;24(31):4908–20.PubMedCrossRef
38.
Yu EJ, Kim SH, Heo K, Ou CY, Stallcup MR, Kim JH. Reciprocal roles of DBC1 and SIRT1 in regulating estrogen receptor alpha activity and co-activator synergy. Nucleic Acids Res. 2011;39(16):6932–43.PubMedCrossRef
39.
40.
41.
Zannini L, Buscemi G, Kim JE, Fontanella E, Delia D. DBC1 phosphorylation by ATM/ATR inhibits SIRT1 deacetylase in response to DNA damage. J Mol Cell Biol. 2012;4(5):294–303.PubMedCrossRef
42.
Menssen A, Hydbring P, Kapelle K, Vervoorts J, Diebold J, Luscher B, et al. The c-MYC oncoprotein, the NAMPT enzyme, the SIRT1-inhibitor DBC1, and the SIRT1 deacetylase form a positive feedback loop. Proc Natl Acad Sci U S A. 2012;109(4):E187–96.PubMedCentralPubMedCrossRef
43.
44.
Trauernicht AM, Kim SJ, Kim NH, Boyer TG. Modulation of estrogen receptor alpha protein level and survival function by DBC-1. Mol Endocrinol. 2007;21(7):1526–36.PubMedCrossRef
45.
Trauernicht AM, Kim SJ, Kim NH, Clarke R, Boyer TG. DBC-1 mediates endocrine resistant breast cancer cell survival. Cell Cycle. 2010;9(6):1218–9.PubMedCrossRef
46.
Kim W, Kim JE. Deleted in breast cancer 1 (DBC1) deficiency results in apoptosis of breast cancer cells through impaired responses to UV-induced DNA damage. Cancer Lett. 2013;333(2):180–6.PubMedCrossRef
47.
Kim SH, Kim JH, Yu EJ, Lee KW, Park CK. The overexpression of DBC1 in esophageal squamous cell carcinoma correlates with poor prognosis. Histol Histopathol. 2012;27(1):49–58.PubMed
48.
Cha EJ, Noh SJ, Kwon KS, Kim CY, Park BH, Park HS, et al. Expression of DBC1 and SIRT1 is associated with poor prognosis of gastric carcinoma. Clin Cancer Res. 2009;15(13):4453–9.PubMedCrossRef
49.
Kim JR, Moon YJ, Kwon KS, Bae JS, Wagle S, Yu TK, et al. Expression of SIRT1 and DBC1 is associated with poor prognosis of soft tissue sarcomas. PLoS One. 2013;8(9):e74738.PubMedCentralPubMedCrossRef
50.
Lee H, Kim KR, Noh SJ, Park HS, Kwon KS, Park BH, et al. Expression of DBC1 and SIRT1 is associated with poor prognosis for breast carcinoma. Hum Pathol. 2011;42(2):204–13.PubMedCrossRef
51.
Noh SJ, Kang MJ, Kim KM, Bae JS, Park HS, Moon WS, et al. Acetylation status of P53 and the expression of DBC1, SIRT1, and androgen receptor are associated with survival in clear cell renal cell carcinoma patients. Pathology. 2013;45(6):574–80.PubMedCrossRef
52.
Park HS, Bae JS, Noh SJ, Kim KM, Lee H, Moon WS, et al. Expression of DBC1 and androgen receptor predict poor prognosis in diffuse large B cell lymphoma. Transl Oncol. 2013;6(3):370–81.PubMedCentralPubMedCrossRef
53.
Sung JY, Kim R, Kim JE, Lee J. Balance between SIRT1 and DBC1 expression is lost in breast cancer. Cancer Sci. 2010;101(7):1738–44. PubMedCrossRef
54.
Zhang Y, Gu Y, Sha S, Kong X, Zhu H, Xu B, et al. DBC1 is over-expressed and associated with poor prognosis in colorectal cancer. Int J Clin Oncol. 2014;19(1):106–12.PubMedCrossRef
55.
Song N, Kim AJ, Kim HJ, Jee HJ, Kim M, Yoo YH, et al. Melatonin suppresses doxorubicin-induced premature senescence of A549 lung cancer cells by ameliorating mitochondrial dysfunction. J Pineal Res. 2012;53(4):335–43. PubMedCrossRef
56.
Fic M, Podhorska-Okolow M, Dziegiel P, Gebarowska E, Wysocka T, Drag-Zalesinska M, et al. Effect of melatonin on cytotoxicity of doxorubicin toward selected cell lines (human keratinocytes, lung cancer cell line A-549, laryngeal cancer cell line Hep-2). In Vivo. 2007;21(3):513–8.PubMed
57.
Stabile LP, Davis AL, Gubish CT, Hopkins TM, Luketich JD, Christie N, et al. Human non-small cell lung tumors and cells derived from normal lung express both estrogen receptor alpha and beta and show biological responses to estrogen. Cancer Res. 2002;62(7):2141–50.PubMed
58.
Mollerup S, Jorgensen K, Berge G, Haugen A. Expression of estrogen receptors alpha and beta in human lung tissue and cell lines. Lung Cancer. 2002;37(2):153–9.PubMedCrossRef
59.
Niikawa H, Suzuki T, Miki Y, Suzuki S, Nagasaki S, Akahira J, et al. Intratumoral estrogens and estrogen receptors in human non-small cell lung carcinoma. Clin Cancer Res. 2008;14(14):4417–26.PubMedCrossRef
60.
Croxtall JD, Emmas C, White JO, Choudhary Q, Flower RJ. Tamoxifen inhibits growth of oestrogen receptor-negative A549 cells. Biochem Pharmacol. 1994;47(2):197–202.PubMedCrossRef
61.
Luo J, Deng ZL, Luo X, Tang N, Song WX, Chen J, et al. A protocol for rapid generation of recombinant adenoviruses using the AdEasy system. Nat Protoc. 2007;2(5):1236–47.PubMedCrossRef
62.
Cucina A, Proietti S, D'Anselmi F, Coluccia P, Dinicola S, Frati L, et al. Evidence for a biphasic apoptotic pathway induced by melatonin in MCF-7 breast cancer cells. J Pineal Res. 2009;46(2):172–80.PubMedCrossRef
63.
64.
Martin-Renedo J, Mauriz JL, Jorquera F, Ruiz-Andres O, Gonzalez P, Gonzalez-Gallego J. Melatonin induces cell cycle arrest and apoptosis in hepatocarcinoma HepG2 cell line. J Pineal Res. 2008;45(4):532–40.PubMedCrossRef
65.
Gerl R, Vaux DL. Apoptosis in the development and treatment of cancer. Carcinogenesis. 2005;26(2):263–70.PubMedCrossRef
66.
Kim JE, Sung S. Deleted in breast cancer 1 (DBC1) is a dynamically regulated protein. Neoplasma. 2010;57(4):365–8.PubMed
67.
Fan W, Luo J. SIRT1 regulates UV-induced DNA repair through deacetylating XPA. Mol Cell. 2010;39(2):247–58.PubMedCrossRef
68.
Cao C, Lu S, Kivlin R, Wallin B, Card E, Bagdasarian A, et al. SIRT1 confers protection against UVB- and H2O2-induced cell death via modulation of p53 and JNK in cultured skin keratinocytes. J Cell Mol Med. 2009;13(9B):3632–43.PubMedCrossRef
69.
Cheng Y, Cai L, Jiang P, Wang J, Gao C, Feng H, et al. SIRT1 inhibition by melatonin exerts antitumor activity in human osteosarcoma cells. Eur J Pharmacol. 2013;715(1–3):219–29.PubMedCrossRef
70.
Jung-Hynes B, Schmit TL, Reagan-Shaw SR, Siddiqui IA, Mukhtar H, Ahmad N. Melatonin, a novel Sirt1 inhibitor, imparts antiproliferative effects against prostate cancer in vitro in culture and in vivo in TRAMP model. J Pineal Res. 2011;50(2):140–9.PubMedCentralPubMed
71.
Luchetti F, Canonico B, Curci R, Battistelli M, Mannello F, Papa S, et al. Melatonin prevents apoptosis induced by UV-B treatment in U937 cell line. J Pineal Res. 2006;40(2):158–67.PubMedCrossRef
72.
Fischer TW, Zbytek B, Sayre RM, Apostolov EO, Basnakian AG, Sweatman TW, et al. Melatonin increases survival of HaCaT keratinocytes by suppressing UV-induced apoptosis. J Pineal Res. 2006;40(1):18–26.PubMedCrossRef
73.
Izykowska I, Cegielski M, Gebarowska E, Podhorska-Okolow M, Piotrowska A, Zabel M, et al. Effect of melatonin on human keratinocytes and fibroblasts subjected to UVA and UVB radiation In vitro. In Vivo. 2009;23(5):739–45.PubMed
74.
Lee KS, Lee WS, Suh SI, Kim SP, Lee SR, Ryoo YW, et al. Melatonin reduces ultraviolet-B induced cell damages and polyamine levels in human skin fibroblasts in culture. Exp Mol Med. 2003;35(4):263–8.PubMedCrossRef
75.
Fischer TW, Kleszczynski K, Hardkop LH, Kruse N, Zillikens D. Melatonin enhances antioxidative enzyme gene expression (CAT, GPx, SOD), prevents their UVR-induced depletion, and protects against the formation of DNA damage (8-hydroxy-2'-deoxyguanosine) in ex vivo human skin. J Pineal Res. 2013;54(3):303–12.PubMedCrossRef
76.
Fischer TW, Scholz G, Knoll B, Hipler UC, Elsner P. Melatonin suppresses reactive oxygen species induced by UV irradiation in leukocytes. J Pineal Res. 2004;37(2):107–12.PubMedCrossRef
77.
Fischer TW, Zmijewski MA, Wortsman J, Slominski A. Melatonin maintains mitochondrial membrane potential and attenuates activation of initiator (casp-9) and effector caspases (casp-3/casp-7) and PARP in UVR-exposed HaCaT keratinocytes. J Pineal Res. 2008;44(4):397–407.PubMedCentralPubMedCrossRef
78.
Kleszczynski K, Hardkop LH, Fischer TW. Differential effects of melatonin as a broad range UV-damage preventive dermato-endocrine regulator. Dermatoendocrinol. 2011;3(1):27–31.PubMedCentralPubMedCrossRef
79.
Srinivasan V, Spence DW, Pandi-Perumal SR, Brown GM, Cardinali DP. Melatonin in mitochondrial dysfunction and related disorders. Int J Alzheimers Dis. 2011;2011:326320.PubMedCentralPubMed
80.
Surendran D, Geetha CS, Mohanan PV. Amelioration of melatonin on oxidative stress and genotoxic effects induced by cisplatin in vitro. Toxicol Mech Methods. 2012;22(8):631–7.PubMedCrossRef
81.
Reiter RJ, Tan DX, Sainz RM, Mayo JC, Lopez-Burillo S. Melatonin: reducing the toxicity and increasing the efficacy of drugs. J Pharm Pharmacol. 2002;54(10):1299–321.PubMedCrossRef
82.
Kim JH, Jeong SJ, Kim B, Yun SM, Choi do Y, Kim SH. Melatonin synergistically enhances cisplatin-induced apoptosis via the dephosphorylation of ERK/p90 ribosomal S6 kinase/heat shock protein 27 in SK-OV-3 cells. J Pineal Res. 2012;52(2):244–52.PubMedCrossRef
83.
Uguz AC, Cig B, Espino J, Bejarano I, Naziroglu M, Rodriguez AB, et al. Melatonin potentiates chemotherapy-induced cytotoxicity and apoptosis in rat pancreatic tumor cells. J Pineal Res. 2012;53(1):91–8.PubMedCrossRef
84.
Fan L, Sun G, Ma T, Zhong F, Lei Y, Li X, et al. Melatonin reverses tunicamycin-induced endoplasmic reticulum stress in human hepatocellular carcinoma cells and improves cytotoxic response to doxorubicin by increasing CHOP and decreasing Survivin. J Pineal Res. 2013;55(2):184–94.PubMedCrossRef
85.
Fan LL, Sun GP, Wei W, Wang ZG, Ge L, Fu WZ, et al. Melatonin and doxorubicin synergistically induce cell apoptosis in human hepatoma cell lines. World J Gastroenterol. 2010;16(12):1473–81.PubMedCentralPubMedCrossRef
Metadata
Title
CCAR2 deficiency augments genotoxic stress-induced apoptosis in the presence of melatonin in non-small cell lung cancer cells
Authors
Wootae Kim
Joo-Won Jeong
Ja-Eun Kim
Publication date
01-11-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 11/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2370-6

Other articles of this Issue 11/2014

Tumor Biology 11/2014 Go to the issue

Research Article

COX-2 overexpression and -8473 T/C polymorphism in 3′ UTR in non-small cell lung cancer

Research Article

Pharmacokinetics of gelatin sponge microparticles in a rabbit VX2 liver tumor model of hepatic arterial chemoembolization

Review

PSA response rate as a surrogate marker for median overall survival in docetaxel-based first-line treatments for patients with metastatic castration-resistant prostate cancer: an analysis of 22 trials

Research Article

Overexpression of CPS1 is an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy

Research Article

The prognosis significance of TGF-β1 and ER protein in cervical adenocarcinoma patients with stage Ib ~ IIa

Research Article

The XRCC1 Arg194Trp and Arg280His polymorphisms in head and neck cancer susceptibility: a meta-analysis
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