nach oben

Investigational New Drugs

Erschienen in:

05.01.2019 | REVIEW

Human antigen R and drug resistance in tumors

verfasst von: Fenghai Zhou, Fa Zhang, Chuan Zhou, Mengtian Liang, Zhonglin Cai, Haidi Lv, Wenjuan Li, Xupan Wei

Erschienen in: Investigational New Drugs | Ausgabe 5/2019

Einloggen, um Zugang zu erhalten

Summary

The human embryonic lethal abnormal visual protein, HuR, belongs to the Hu family of RNA-binding proteins. Over the past two decades, HuR has been extensively associated with multiple biological characteristics of tumors, including tumor development and progression, angiogenesis, invasion, migration and prognosis, since this protein regulates the stability of cancer-associated target mRNAs due to its posttranscriptional regulatory mechanisms. A recent investigation of the multiple functions of HuR has provided emerging evidence of its role in drug resistance in various tumors. Herein, we demonstrate the roles of HuR proteins in the development of drug resistance, examine their involvement in various mechanisms, including apoptosis, the ABC transporter family, the cell cycle and the DNA damage response, and provide insight into ongoing studies for developing therapeutic strategies aimed at targeting this molecule in tumor cells.

Robinow S, Campos AR, Yao KM (1988) The elav gene product of drosophila, required in neurons, has three RNP consensus motifs. Science 242(4885):1570–1572CrossRefPubMed

von Roretz C, Di Marco S, Mazroui R (2011) Turnover of AU-rich-containing mRNAs during stress: a matter of survival. Wiley Interdiscip Rev RNA 2(3):336–347CrossRef

Embade N, Fernández-Ramos D, Varela-Rey M, Beraza N, Sini M, de Juan VG, Woodhoo A, Martínez-López N, Rodríguez-Iruretagoyena B, Bustamante FJ, de la Hoz AB, Carracedo A, Xirodimas DP, Rodríguez MS, Lu SC, Mato JM, Martínez-Chantar ML (2012) Murine double minute 2 regulates Hu antigen R stability in human liver and colon cancer through NEDDylation. Hepatology 55(4):1237–1248CrossRefPubMedPubMedCentral

de Sousa GF, Lima Mde A, Custodio DF et al (2015) Chemogenomic study of carboplatin in Saccharomyces cerevisiae: inhibition of the NEDDylation process overcomes cellular resistance mediated by HuR and Cullin proteins. PLoS One 10(12):e0145377CrossRefPubMedPubMedCentral

Jeyaraj SC, Singh M, Ayupova DA, Govindaraju S, Lee BS (2010) Transcriptional control of human antigen R by bone morphogenetic protein. J Biol Chem 285(7):4432–4440CrossRefPubMed

Cho SJ, Zhang J, Chen X (2010) RNPC1 modulates the RNA-binding activity of, and cooperates with, HuR to regulate p21 mRNA stability. Nucleic Acids Res 38(7):2256–2267CrossRefPubMedPubMedCentral

Cho SJ, Jung YS, Zhang J, Chen X (2012) The RNA-binding protein RNPC1 stabilizes the mRNA encoding the RNA-binding protein HuR and cooperates with HuR to suppress cell proliferation. J Biol Chem 287(18):14535–14544CrossRefPubMedPubMedCentral

Gabai VL, Meng L, Kim G, Mills TA, Benjamin IJ, Sherman MY (2012) Heat shock transcription factor Hsf1 is involved in tumor progression via regulation of hypoxia-inducible factor 1 and RNA-binding protein HuR. Mol Cell Biol 32(5):929–940CrossRefPubMedPubMedCentral

Winkler C (2014) Doller A, Imre G, et al. Attenuation of the ELAV1-like protein HuR sensitizes adenocarcinoma cells to the intrinsic apoptotic pathway by increasing the translation of caspase-2L. Cell Death Dis 5:e1321CrossRefPubMedPubMedCentral

10.

Griffiths-Jones S, Saini HK, Van Dongen S et al (2008) miR base: tools for microRNA genomics. Nucleic Acids Res 36:D154–D158CrossRefPubMed

11.

Bhattacharyya SN, Habermacher R, Martine U, Closs EI, Filipowicz W (2006) Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell 125(6):1111–1124CrossRefPubMed

12.

Srikantan S, Abdelmohsen K, Lee EK, Tominaga K, Subaran SS, Kuwano Y, Kulshrestha R, Panchakshari R, Kim HH, Yang X, Martindale JL, Marasa BS, Kim MM, Wersto RP, Indig FE, Chowdhury D, Gorospe M (2011) Translational control of TOP2A influences doxorubicin efficacy. Mol Cell Biol 31(18):3790–3801CrossRefPubMedPubMedCentral

13.

Tominaga K, Srikantan S, Lee EK, Subaran SS, Martindale JL, Abdelmohsen K, Gorospe M (2011) Competitive regulation of nucleolin expression by HuR and miR-494. Mol Cell Biol 31(20):4219–4231CrossRefPubMedPubMedCentral

14.

Jakstaite A, Maziukiene A, Silkuniene G et al (2015) HuR mediated post-transcriptional regulation as a new potential adjuvant therapeutic target in chemotherapy for pancreatic cancer. World J Gastroenterol 21(46):13004–13019CrossRefPubMedPubMedCentral

15.

Blanco FF, Jimbo M, Wulfkuhle J et al (2016) The mRNA-binding protein HuR promotes hypoxia-induced chemoresistance through posttranscriptional regulation of the proto-oncogene PIM1 in pancreatic cancer cells. Oncogene 35(19):41CrossRef

16.

Romeo C, Weber MC, Zarei M, DeCicco D, Chand SN, Lobo AD, Winter JM, Sawicki JA, Sachs JN, Meisner-Kober N, Yeo CJ, Vadigepalli R, Tykocinski ML, Brody JR (2016) HuR contributes to TRAIL resistance by restricting death receptor 4 expression in pancreatic cancer cells. Mol Cancer Res 14(7):599–611CrossRefPubMedPubMedCentral

17.

Costantino CL, Witkiewicz AK, Kuwano Y, Cozzitorto JA, Kennedy EP, Dasgupta A, Keen JC, Yeo CJ, Gorospe M, Brody JR (2009) The role of HuR in gemcitabine efficacy in pancreatic cancer: HuR up-regulates the expression of the gemcitabine metabolizing enzyme deoxycytidine kinase. Cancer Res 69(11):4567–4572CrossRefPubMedPubMedCentral

18.

Wu Q, Yang Z, Xia L et al (2014) Methylation of miR-129-5p CpG island modulates multi-drug resistance in gastric cancer by targeting ABC transporters. Oncotarget 5:11552–11563PubMedPubMedCentral

19.

Teodori E, Dei S, Martelli C, Scapecchi S, Gualtieri F (2006) The functions and structure of ABC transporters: implications for the design of new inhibitors of Pgp and MRP1 to control multidrug resistance (MDR). Curr Drug Targets 7(7):893–909CrossRefPubMed

20.

Li S, Zhang W, Yin X, Xing S, Xie H, Cao Z, Zhao B (2015) Mouse ATP-binding cassette (ABC) transporters conferring multi-drug resistance. Anti Cancer Agents Med Chem 15(4):423–432CrossRef

21.

Shang Y, Zhang Z, Liu Z, Feng B, Ren G, Li K, Zhou L, Sun Y, Li M, Zhou J, An Y, Wu K, Nie Y, Fan D (2014) miR-508-5p regulates multidrug resistance of gastric cancer by targeting ABCB1 and ZNRD1. Oncogene 33:3267–3276CrossRefPubMed

22.

To KK, Leung WW, Ng SS et al (2015) Exploiting a novel miR-519c-HuR-ABCG2 regulatory pathway to overcome chemoresistance in colorectal cancer. Exp Cell Res 338(2):222–231CrossRefPubMed

23.

Liu H, Song X, Hou J, Zhao Z, Chang J (2018) Posttranscriptional regulation of human antigen R by miR-133b enhances docetaxel cytotoxicity through the inhibition of ATP-binding cassette subfamily G member 2 in prostate cancer cells. DNA Cell Biol 37(3):210–219CrossRefPubMed

24.

Bhatnagar N, Li X, Padi SK et al (2010) Downregulation of miR-205 and miR-31 confers resistance to chemotherapy-induced apoptosis in prostate cancer cells. Cell Death Dis 1:e105CrossRefPubMedPubMedCentral

25.

Puhr M, Hoefer J, Schäfer G, Erb HHH, Oh SJ, Klocker H, Heidegger I, Neuwirt H, Culig Z (2012) Epithelial-to-mesenchymal transition leads to docetaxel resistance in prostate cancer and is mediated by reduced expression of miR-200c and miR-205. Am J Pathol 181(6):2188–2201CrossRefPubMed

26.

Yang Y, Jia D, Kim H, Abd Elmageed ZY, Datta A, Davis R, Srivastav S, Moroz K, Crawford BE, Moparty K, Thomas R, Hudson RS, Ambs S, Abdel-Mageed AB (2016) Dysregulation of miR-212 promotes castration resistance through hnRNPH1-mediated regulation of AR and AR-V7: implications for racial disparity of prostate cancer. Clin Cancer Res 22(7):1744–1756CrossRefPubMed

27.

Feng B, Wang R, Chen LB (2012) Review of MiR-200b and cancer chemosensitivity. Biomed Pharmacother 66:397–402CrossRefPubMed

28.

Shi GH, Ye DW, Yao XD, Zhang SL, Dai B, Zhang HL, Shen YJ, Zhu Y, Zhu YP, Xiao WJ, Ma CG (2010) Involvement of microRNA-21 in mediating chemo-resistance to docetaxel in androgen-independent prostate cancer PC3 cells. Acta Pharmacol Sin 31(7):867–873CrossRefPubMedPubMedCentral

29.

Liao H, Xiao Y, Hu Y et al (2016) Methylation-induced silencing of miR-34a enhances chemoresistance by directly upregulating ATG4B-induced autophagy through AMPK/mTOR pathway in prostate cancer. Oncol Rep 35(1):64–72CrossRefPubMed

30.

Wen D, Peng Y, Lin F, Singh RK, Mahato RI (2017) Micellar delivery of miR-34a modulator Rubone and paclitaxel in resistant prostate cancer. Cancer Res 77(12):3244–3254CrossRefPubMedPubMedCentral

31.

Armstrong CM, Liu C, Lou W, Lombard AP, Evans CP, Gao AC (2017) MicroRNA-181a promotes docetaxel resistance in prostate cancer cells. Prostate 77(9):1020–1028CrossRefPubMedPubMedCentral

32.

Ma X, Zou L, Li X, Chen Z, Lin Q, Wu X (2018) MicroRNA-195 regulates docetaxel resistance by targeting clusterin in prostate cancer. Biomed Pharmacother 99:445–450CrossRefPubMed

33.

Fujita Y, Kojima T, Kawakami K, Mizutani K, Kato T, Deguchi T, Ito M (2015) miR-130a activates apoptotic signaling through activation of caspase-8 in taxane-resistant prostate cancer cells. Prostate 75(14):1568–1578CrossRefPubMed

34.

Xu B, Niu X, Zhang X et al (2011) miR-143 decreases prostate cancer cells proliferation and migration and enhances their sensitivity to docetaxel through suppression of KRAS. Mol Cell Biochem 50(1–2):207–213CrossRef

35.

Fujita Y, Kojima K, Ohhashi R, Hamada N, Nozawa Y, Kitamoto A, Sato A, Kondo S, Kojima T, Deguchi T, Ito M (2010) MiR-148a attenuates paclitaxel resistance of hormone-refractory, drug-resistant prostate cancer PC3 cells by regulating MSK1 expression. J Biol Chem 285(25):19076–19084CrossRefPubMedPubMedCentral

36.

Chen L, Cao H, Feng Y (2018) MiR-199a suppresses prostate cancer paclitaxel resistance by targeting YES1. World J Urol 36(3):357–365CrossRefPubMed

37.

Wang Y, Lieberman R, Pan J et al (2016) miR-375 induces docetaxel resistance in prostate cancer by targeting SEC23A and YAP1. Mol Cancer 15(1):70CrossRefPubMedPubMedCentral

38.

Li B, Jin X, Meng H et al (2017) Morin promotes prostate cancer cells chemosensitivity to paclitaxel through miR-155/GATA3 axis. Oncotarget 8(29):47849–47860PubMedPubMedCentral

39.

Wang X, Yang B, Ma B et al (2016) The UCA1/miR-204/Sirt1 axis modulates docetaxel sensitivity of prostate cancer cells. Cancer Chemother Pharmacol 78(5):1025–1031CrossRefPubMed

40.

Lin GL, Ting HJ, Tseng TC et al (2017) Modulation of the mRNA-binding protein HuR as a novel reversal mechanism of epirubicin-triggered multidrug resistance in colorectal cancer cells. PLoS ONE 12(10):e0185625CrossRefPubMedPubMedCentral

41.

Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116(2):205–219CrossRefPubMed

42.

Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70CrossRef

43.

Ashkenazi A (2008) Directing cancer cells to self-destruct with pro-apoptotic receptor agonists. Nat Rev Drug Discov 7(12):1001–1012CrossRefPubMed

44.

Coultas L, Strasser A (2003) The role of the Bcl-2 protein family in cancer. Semin Cancer Biol 13(2):115–123CrossRefPubMed

45.

Letai A (2005) Pharmacological manipulation of Bcl-2 family members to control cell death. J Clin Invest 115(10):2648–2655CrossRefPubMedPubMedCentral

46.

Filippova N, Yang X, Wang Y, Gillespie GY, Langford C, King PH, Wheeler C, Nabors LB (2011) The RNA-binding protein HuR promotes glioma growth and treatment resistance. Mol Cancer Res 9(5):648–659CrossRefPubMedPubMedCentral

47.

Korshunov A, Golanov A, Sycheva R, Pronin I (1999) Prognostic value of tumour associated antigen immunoreactivity and apoptosis in cerebral glioblastomas: an analysis of 168 cases. J Clin Pathol 52(8):574–580CrossRefPubMedPubMedCentral

48.

Streffer JR, Rimner A, Rieger J, Naumann U, Rodemann HP, Weller M (2002) BCL-2 family proteins modulate radiosensitivity in human malignant glioma cells. J Neurooncol 56(1):43–49CrossRefPubMed

49.

Muralidharan R, Mehta M, Ahmed R, Roy S, Xu L, Aubé J, Chen A, Zhao YD, Herman T, Ramesh R, Munshi A (2017) HuR-targeted small molecule inhibitor exhibits cytotoxicity towards human lung cancer cells. Sci Rep 7(1):9694CrossRefPubMedPubMedCentral

50.

Badawi A, Biyanee A, Nasrullah U et al (2018) Inhibition of IRES-dependent translation of caspase-2 by HuR confers chemotherapeutic drug resistance in colon carcinoma cells. Oncotarget 9(26):18367–18385CrossRefPubMedPubMedCentral

51.

Kojima K, Fujita Y, Nozawa Y, Deguchi T, Ito M (2010) MiR-34a attenuates paclitaxel-resistance of hormone-refractory prostate cancer PC3 cells through direct and indirect mechanisms. Prostate 70(14):1501–1512CrossRefPubMed

52.

Goldie JH, Coldman AJ (1979) A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep 63(11–12):1727–1733PubMed

53.

Sherr CJ, Roberts JM (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13(12):1501–1512CrossRef

54.

Slingerland J, Pagano M (2000) Regulation of the cdk inhibitor p27 and its deregulation in cancer. J Cell Physiol 183(1):10–17CrossRefPubMed

55.

Sherr CJ (1994) G1 phase progression: cycling on cue. Cell 79(4):551–555CrossRefPubMed

56.

Alkarain A, Jordan R, Slingerland J (2004) p27 deregulation in breast cancer: prognostic significance and implications for therapy. J Mammary Gland Biol Neoplasia 9(1):67–80CrossRefPubMed

57.

Toyoshima H, Hunter T (1994) p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell 78(1):67–74CrossRef

58.

Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D (1993) p21 is a universal inhibitor of cyclin kinases. Nature 366(6456):701–704CrossRefPubMed

59.

Cheng JD, Werness BA et al (1999) Paradoxical correlations of cyclin-dependent kinase inhibitors p21waf1/cip1 and p27kip1 in metastatic colorectal carcinoma. Clin Cancer Res 5(5):1057–1062PubMed

60.

Shiloh Y (2003) ATM and related protein kinases: safeguarding genome integrity. Nat Rev 3(3):155–168CrossRef

61.

Bargonetti J, Manfredi JJ (2002) Multiple roles of the tumor suppressor p53. Curr Opin Oncol 14:86–91CrossRef

62.

Guertin AD, Li J, Liu Y, Hurd MS, Schuller AG, Long B, Hirsch HA, Feldman I, Benita Y, Toniatti C, Zawel L, Fawell SE, Gilliland DG, Shumway SD (2013) Preclinical evaluation of the WEE1 inhibitor MK-1775 as single-agent anticancer therapy. Mol Cancer Ther 12(8):1442–1452CrossRefPubMed

63.

Lal S, Burkhart RA, Beeharry N, Bhattacharjee V, Londin ER, Cozzitorto JA, Romeo C, Jimbo M, Norris ZA, Yeo CJ, Sawicki JA, Winter JM, Rigoutsos I, Yen TJ, Brody JR (2014) HuR posttranscriptionally regulates WEE1: implications for the DNA damage response in pancreatic cancer cells. Cancer Res 74(4):1128–1140CrossRefPubMedPubMedCentral

64.

D'Amours D, Desnoyers S, D'Silva I, Poirier GG (1999) Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J 342(Pt 2):249–268CrossRefPubMedPubMedCentral

65.

Bouwman P, Jonkers J (2014) Molecular pathways: how can BRCA-mutated tumors become resistant to PARP inhibitors? Clin Cancer Res 20:540–547CrossRefPubMed

66.

Johnson N, Johnson SF, Yao W, Li YC, Choi YE, Bernhardy AJ, Wang Y, Capelletti M, Sarosiek KA, Moreau LA, Chowdhury D, Wickramanayake A, Harrell MI, Liu JF, D'Andrea AD, Miron A, Swisher EM, Shapiro GI (2013) Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance. Proc Natl Acad Sci U S A 110:17041–17046CrossRefPubMedPubMedCentral

67.

Chand SN, Zarei M, Schiewer MJ et al (2017) Posttranscriptional regulation of PARG mRNA by HuR facilitates DNA repair and resistance to PARP inhibitors. Cancer Res 77(18):5011–5025CrossRefPubMedPubMedCentral

68.

Guo J, Lv J, Chang S (2016) Inhibiting cytoplasmic accumulation of HuR synergizes genotoxic agents in urothelial carcinoma of the bladder. Oncotarget 7(29):45249–45262CrossRefPubMedPubMedCentral

69.

Hill R, Li Y, Tran LM, Dry S, Calvopina JH, Garcia A, Kim C, Wang Y, Donahue TR, Herschman HR, Wu H (2012) Cell intrinsic role of COX-2 in pancreatic cancer development[J]. Mol Cancer Ther 11(10):2127–2137CrossRefPubMedPubMedCentral

70.

Richards NG, Rittenhouse DW, Freydin B et al (2010) HuR status is a powerful marker for prognosis and response to gemcitabine-based chemotherapy for resected pancreatic ductal adenocarcinoma patients. Ann Surg 252(3):499–505PubMed

71.

Janakiraman H, House RP, Talwar S et al (2017) Repression of caspase-3 and RNA-binding protein HuR cleavage by cyclooxygenase-2 promotes drug resistance in oral squamous cell carcinoma. Oncogene 36(22):3137–3148CrossRefPubMed

72.

Ayala GE, Dai H, Ittmann M, Li R, Powell M, Frolov A, Wheeler TM, Thompson TC, Rowley D (2004) Growth and survival mechanisms associated with perineural invasion in prostate cancer. Cancer Res 64:6082–6090CrossRefPubMed

73.

Zarei M (2017) Lal S1, Parker SJ, et al. posttranscriptional upregulation of IDH1 by HuR establishes a powerful survival phenotype in pancreatic cancer cells. Cancer Res 77(16):4460–4471CrossRefPubMedPubMedCentral

74.

Williams TK, Costantino CL, Bildzukewicz NA et al (2010) pp32 (ANP32A) expression inhibits pancreatic cancer cell growth and induces gemcitabine resistance by disrupting HuR binding to mRNAs. PLoS One 5(11):e15455CrossRefPubMedPubMedCentral

75.

Latorre E, Tebaldi T, Viero G, Spartà A, Quattrone A, Provenzani A (2012) Downregulation of HuR as a new mechanism of doxorubicin resistance in breast cancer cells. Mol Cancer 11:13CrossRefPubMedPubMedCentral

76.

Zhou Y, Chang R, Ji W, Wang N, Qi M, Xu Y, Guo J, Zhan L (2016) Loss of scribble promotes snail translation through translocation of HuR and enhances cancer drug resistance. J Biol Chem 291(1):291–302CrossRefPubMed

77.

Heinonen M, Bono P, Narko K (2005) Cytoplasmic HuR expression is a prognostic factor in invasive ductal breast carcinoma. Cancer Res 65(6):2157–2161CrossRefPubMed

78.

Lim SJ, Kim HJ, Kim JY (2007) Expression of HuR is associated with increased cyclooxygenase-2 expression in uterine cervical carcinoma. Int J Gynecol Pathol 26(3):229–234CrossRefPubMed

79.

Kurosu T, Ohga N, Hida Y (2011) HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium. Br J Cancer 104(5):819–829CrossRefPubMedPubMedCentral

80.

Cha JD, Li S, Cha IH (2011) Association between expression of embryonic lethal abnormal vision-like protein HuR and cyclooxygenase-2 in oral squamous cell carcinoma. Head Neck 33(5):627–637CrossRefPubMed

81.

Zhu Z, Wang B, Bi J (2013) Cytoplasmic HuR expression correlates with P-gp, HER-2 positivity, and poor outcome in breast cancer. Tumour Biol 34(4):2299–2308CrossRefPubMed

Titel: Human antigen R and drug resistance in tumors
verfasst von: Fenghai Zhou
Fa Zhang
Chuan Zhou
Mengtian Liang
Zhonglin Cai
Haidi Lv
Wenjuan Li
Xupan Wei
Publikationsdatum: 05.01.2019
Verlag: Springer US
Erschienen in: Investigational New Drugs / Ausgabe 5/2019
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-018-00723-x

Neu im Fachgebiet Onkologie

24.04.2024 | DGIM 2024 | Nachrichten

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Human antigen R and drug resistance in tumors

Summary

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Summary

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2019

The antitumor efficacy of monomeric disintegrin obtustatin in S-180 sarcoma mouse model

In vitro and in vivo cytotoxic activity and human serum albumin interaction for a methoxy-styryl-thiosemicarbazone

Nifuroxazide induces apoptosis, inhibits cell migration and invasion in osteosarcoma

MiR-181a, a new regulator of TGF-β signaling, can promote cell migration and proliferation in gastric cancer

The cellular effects of novel triazine nitrogen mustards in glioblastoma LBC3, LN-18 and LN-229 cell lines

The novel PI3K inhibitor S1 synergizes with sorafenib in non-small cell lung cancer cells involving the Akt-S6 signaling

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie