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Virchows Archiv

Erschienen in:

10.03.2017 | Invited Annual Review Issue

Molecular mechanisms of therapy resistance in solid tumors: chasing “moving” targets

verfasst von: Laura J. Tafe

Erschienen in: Virchows Archiv | Ausgabe 2/2017

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Abstract

The goal of personalized cancer therapy is to treat tumors based on genomic aberrations that drive their survival and progression. Most patients who receive targeted therapies typically develop resistance and disease progression within a year’s time. This review focuses on the heterogeneous mechanisms of therapy resistance to tyrosine kinase inhibitors, endocrine/hormone therapy and checkpoint blockade using non-small cell lung cancer, breast and castration-resistant prostate cancer, and melanoma as classical examples, respectively. In addition, testing for resistance mechanisms and therapeutic approaches to overcoming resistance is addressed.

Pao W, Miller V, Zakowski M et al (2004) EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 101(36):13306–13311. doi:10.1073/pnas.0405220101 CrossRefPubMedPubMedCentral

Lynch TJ, Bell DW, Sordella R et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350(21):2129–2139. doi:10.1056/NEJMoa040938 CrossRefPubMed

Ohashi K, Maruvka YE, Michor F, Pao W (2013) Epidermal growth factor receptor tyrosine kinase inhibitor-resistant disease. J Clin Oncol 31(8):1070–1080. doi:10.1200/JCO.2012.43.3912 CrossRefPubMedPubMedCentral

Engelman JA, Janne PA (2008) Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Clin Cancer Res 14(10):2895–2899. doi:10.1158/1078-0432.CCR-07-2248 CrossRefPubMed

Wang J, Wang B, Chu H, Yao Y (2016) Intrinsic resistance to EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer with activating EGFR mutations. Onco Targets Ther. 9:3711–3726. doi:10.2147/OTT.S106399 CrossRefPubMedPubMedCentral

Sforza V, Martinelli E, Ciardiello F et al (2016) Mechanisms of resistance to anti-epidermal growth factor receptor inhibitors in metastatic colorectal cancer. World J Gastroenterol 22(28):6345–6361. doi:10.3748/wjg.v22.i28.6345 CrossRefPubMedPubMedCentral

Arcila ME, Nafa K, Chaft JE et al (2013) EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther 12(2):220–229. doi:10.1158/1535-7163.MCT-12-0620 CrossRefPubMedPubMedCentral

Jackman D, Pao W, Riely GJ et al (2010) Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol 28(2):357–360. doi:10.1200/JCO.2009.24.7049 CrossRefPubMed

Camidge DR, Pao W, Sequist LV (2014) Acquired resistance to TKIs in solid tumours: learning from lung cancer. Nat Rev Clin Oncol 11(8):473–481. doi:10.1038/nrclinonc.2014.104 CrossRefPubMed

10.

Yu HA, Arcila ME, Rekhtman N et al (2013) Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res 19(8):2240–2247. doi:10.1158/1078-0432.CCR-12-2246 CrossRefPubMedPubMedCentral

11.

Belchis DA, Tseng LH, Gniadek T et al (2016) Heterogeneity of resistance mutations detectable by nextgeneration sequencing in TKI-treated lung adenocarcinoma. Oncotarget 7(29):45237–45248. doi:10.18632/oncotarget.9931 CrossRefPubMedPubMedCentral

12.

Yun CH, Mengwasser KE, Toms AV et al (2008) The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A 105(6):2070–2075. doi:10.1073/pnas.0709662105 CrossRefPubMedPubMedCentral

13.

Pao W, Miller VA, Politi KA et al (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2(3):e73CrossRefPubMedPubMedCentral

14.

Suda K, Mizuuchi H, Maehara Y, Mitsudomi T (2012) Acquired resistance mechanisms to tyrosine kinase inhibitors in lung cancer with activating epidermal growth factor receptor mutation—diversity, ductility, and destiny. Cancer Metastasis Rev 31(3–4):807–814. doi:10.1007/s10555-012-9391-7 CrossRefPubMed

15.

Hata AN, Niederst MJ, Archibald HL et al (2016) Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition. Nat Med 22(3):262–269. doi:10.1038/nm.4040 CrossRefPubMedPubMedCentral

16.

Gainor JF, Dardaei L, Yoda S et al (2016) Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer. Cancer Discov. 6(10):1118–1133CrossRefPubMed

17.

Facchinetti F, Loriot Y, Kuo MS et al (2016) Crizotinib-resistant ROS1 mutations reveal a predictive kinase inhibitor sensitivity model for ROS1- and ALK-rearranged lung cancers. Clin Cancer Res 22(24):5983–5991CrossRefPubMed

18.

Engelman JA, Zejnullahu K, Mitsudomi T et al (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316(5827):1039–1043CrossRefPubMed

19.

Takezawa K, Pirazzoli V, Arcila ME et al (2012) HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutation. Cancer Discov. 2(10):922–933. doi:10.1158/2159-8290.CD-12-0108 CrossRefPubMedPubMedCentral

20.

Levacq D, D'Haene N, de Wind R, Remmelink M, Berghmans T (2016) Histological transformation of ALK rearranged adenocarcinoma into small cell lung cancer: a new mechanism of resistance to ALK inhibitors. Lung Cancer 102:38–41CrossRefPubMed

21.

Oser MG, Niederst MJ, Sequist LV, Engelman JA (2015) Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin. Lancet Oncol 16(4):e165–e172. doi:10.1016/S1470-2045(14)71180-5 CrossRefPubMedPubMedCentral

22.

Tatematsu A, Shimizu J, Murakami Y et al (2008) Epidermal growth factor receptor mutations in small cell lung cancer. Clin Cancer Res 14(19):6092–6096. doi:10.1158/1078-0432.CCR-08-0332 CrossRefPubMed

23.

Shiao TH, Chang YL, Yu CJ et al (2011) Epidermal growth factor receptor mutations in small cell lung cancer: a brief report. J Thorac Oncol 6(1):195–198. doi:10.1097/JTO.0b013e3181f94abb CrossRefPubMed

24.

George J, Lim JS, Jang SJ et al (2015) Comprehensive genomic profiles of small cell lung cancer. Nature 524(7563):47–53. doi:10.1038/nature14664 CrossRefPubMedPubMedCentral

25.

Rudin CM, Durinck S, Stawiski EW et al (2012) Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet 44(10):1111–1116. doi:10.1038/ng.2405 CrossRefPubMedPubMedCentral

26.

Peifer M, Fernandez-Cuesta L, Sos ML et al (2012) Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet 44(10):1104–1110. doi:10.1038/ng.2396 CrossRefPubMedPubMedCentral

27.

Niederst MJ, Sequist LV, Poirier JT et al (2015) RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat Commun 6:6377. doi:10.1038/ncomms7377 CrossRefPubMedPubMedCentral

28.

Dorantes-Heredia R, Ruiz-Morales JM, Cano-Garcia F (2016) Histopathological transformation to small-cell lung carcinoma in non-small cell lung carcinoma tumors. Transl Lung Cancer Res 5(4):401–412. doi:10.21037/tlcr.2016.07.10 CrossRefPubMedPubMedCentral

29.

Meder L, Konig K, Ozretic L et al (2016) NOTCH, ASCL1, p53 and RB alterations define an alternative pathway driving neuroendocrine and small cell lung carcinomas. Int J Cancer 138(4):927–938. doi:10.1002/ijc.29835 CrossRefPubMed

30.

Sutherland KD, Proost N, Brouns I, Adriaensen D, Song JY, Berns A (2011) Cell of origin of small cell lung cancer: inactivation of Trp53 and Rb1 in distinct cell types of adult mouse lung. Cancer Cell 19(6):754–764. doi:10.1016/j.ccr.2011.04.019 CrossRefPubMed

31.

Mainardi S, Mijimolle N, Francoz S, Vicente-Duenas C, Sanchez-Garcia I, Barbacid M (2014) Identification of cancer initiating cells in K-ras driven lung adenocarcinoma. Proc Natl Acad Sci U S A 111(1):255–260. doi:10.1073/pnas.1320383110 CrossRefPubMed

32.

Sutherland KD, Song JY, Kwon MC, Proost N, Zevenhoven J, Berns A (2014) Multiple cells-of-origin of mutant K-ras-induced mouse lung adenocarcinoma. Proc Natl Acad Sci U S A 111(13):4952–4957. doi:10.1073/pnas.1319963111 CrossRefPubMedPubMedCentral

33.

Polyak K, Weinberg RA (2009) Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 9(4):265–273. doi:10.1038/nrc2620 CrossRefPubMed

34.

Thiery JP, Acloque H, Huang RY, Nieto MA (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139(5):871–890. doi:10.1016/j.cell.2009.11.007 CrossRefPubMed

35.

Brabletz S, Brabletz T (2010) The ZEB/miR-200 feedback loop—a motor of cellular plasticity in development and cancer? EMBO Rep 11(9):670–677. doi:10.1038/embor.2010.117 CrossRefPubMedPubMedCentral

36.

Nurwidya F, Takahashi F, Murakami A, Takahashi K (2012) Epithelial mesenchymal transition in drug resistance and metastasis of lung cancer. Cancer Res Treat 44(3):151–156. doi:10.4143/crt.2012.44.3.151 CrossRefPubMedPubMedCentral

37.

Sequist LV, Waltman BA, Dias-Santagata D, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med. 2011;3(75):75ra26. doi: 10.1126/scitranslmed.3002003.

38.

Yauch RL, Januario T, Eberhard DA et al (2005) Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients. Clin Cancer Res 11(24 Pt 1):8686–8698CrossRefPubMed

39.

Larsen JE, Nathan V, Osborne JK et al (2016) ZEB1 drives epithelial-to-mesenchymal transition in lung cancer. J Clin Invest 126(9):3219–3235. doi:10.1172/JCI76725 CrossRefPubMedPubMedCentral

40.

Kitai H, Ebi H. Key roles of EMT for adaptive resistance to MEK inhibitor in KRAS mutant lung cancer. Small GTPases. 2016;1–5. doi: 10.1080/21541248.2016.1210369

41.

Reka AK, Kurapati H, Narala VR et al (2010) Peroxisome proliferator-activated receptor-gamma activation inhibits tumor metastasis by antagonizing Smad3-mediated epithelial-mesenchymal transition. Mol Cancer Ther 9(12):3221–3232. doi:10.1158/1535-7163.MCT-10-0570 CrossRefPubMedPubMedCentral

42.

Wang H, Zhang H, Tang L et al (2013) Resveratrol inhibits TGF-beta1-induced epithelial-to-mesenchymal transition and suppresses lung cancer invasion and metastasis. Toxicology 303:139–146. doi:10.1016/j.tox.2012.09.017 CrossRefPubMed

43.

Watson PA, Arora VK, Sawyers CL (2015) Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat Rev Cancer 15(12):701–711. doi:10.1038/nrc4016 CrossRefPubMedPubMedCentral

44.

Ladd B, Mazzola AM, Bihani T et al (2016) Effective combination therapies in preclinical endocrine resistant breast cancer models harboring ER mutations. Oncotarget. doi:10.18632/oncotarget.10852

45.

Jeselsohn R, Buchwalter G, De Angelis C, Brown M, Schiff R (2015) ESR1 mutations—a mechanism for acquired endocrine resistance in breast cancer. Nat Rev Clin Oncol 12(10):573–583. doi:10.1038/nrclinonc.2015.117 CrossRefPubMedPubMedCentral

46.

Niu J, Andres G, Kramer K et al (2015) Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients. Onco Targets Ther 8:3323–3328. doi:10.2147/OTT.S92443 CrossRefPubMedPubMedCentral

47.

Angus L, Beije N, Jager A, Martens JW, Sleijfer S (2016) ESR1 mutations: moving towards guiding treatment decision-making in metastatic breast cancer patients. Cancer Treat Rev 52:33–40CrossRefPubMed

48.

Offermann A, Vlasic I, Syring I et al (2016) MED15 overexpression in prostate cancer arises during androgen deprivation therapy via PI3K/mTOR signaling. Oncotarget. doi:10.18632/oncotarget.13860

49.

Tran C, Ouk S, Clegg NJ et al (2009) Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 324(5928):787–790. doi:10.1126/science.1168175 CrossRefPubMedPubMedCentral

50.

Robinson D, Van Allen EM, Wu YM et al (2015) Integrative clinical genomics of advanced prostate cancer. Cell 161(5):1215–1228. doi:10.1016/j.cell.2015.05.001 CrossRefPubMedPubMedCentral

51.

Pritchard CC, Mateo J, Walsh MF et al (2016) Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med 375(5):443–453. doi:10.1056/NEJMoa1603144 CrossRefPubMedPubMedCentral

52.

Beltran H, Yelensky R, Frampton GM et al (2013) Targeted next-generation sequencing of advanced prostate cancer identifies potential therapeutic targets and disease heterogeneity. Eur Urol 63(5):920–926. doi:10.1016/j.eururo.2012.08.053 CrossRefPubMed

53.

Castro E, Mateo J, Olmos D, de Bono JS (2016) Targeting DNA repair: the role of PARP inhibition in the treatment of castration-resistant prostate cancer. Cancer J 22(5):353–356. doi:10.1097/PPO.0000000000000219 CrossRef

54.

Antonarakis ES, Lu C, Wang H et al (2014) AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 371(11):1028–1038. doi:10.1056/NEJMoa1315815 CrossRefPubMedPubMedCentral

55.

Welti J, Rodrigues DN, Sharp A et al (2016) Analytical validation and clinical qualification of a new immunohistochemical assay for androgen receptor splice variant-7 protein expression in metastatic castration-resistant prostate cancer. Eur Urol 70(4):599–608CrossRefPubMedPubMedCentral

56.

Sharma A, Yeow WS, Ertel A et al (2010) The retinoblastoma tumor suppressor controls androgen signaling and human prostate cancer progression. J Clin Invest 120(12):4478–4492. doi:10.1172/JCI44239 CrossRefPubMedPubMedCentral

57.

Beltran H, Prandi D, Mosquera JM et al (2016) Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat Med 22(3):298–305. doi:10.1038/nm.4045 CrossRefPubMedPubMedCentral

58.

Tan HL, Sood A, Rahimi HA et al (2014) Rb loss is characteristic of prostatic small cell neuroendocrine carcinoma. Clin Cancer Res 20(4):890–903. doi:10.1158/1078-0432.CCR-13-1982 CrossRefPubMed

59.

Beltran H, Rickman DS, Park K et al (2011) Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer Discov. 1(6):487–495. doi:10.1158/2159-8290.CD-11-0130 CrossRefPubMedPubMedCentral

60.

Hansel DE, Nakayama M, Luo J et al (2009) Shared TP53 gene mutation in morphologically and phenotypically distinct concurrent primary small cell neuroendocrine carcinoma and adenocarcinoma of the prostate. Prostate 69(6):603–609. doi:10.1002/pros.20910 CrossRefPubMedPubMedCentral

61.

Arcila ME, Oxnard GR, Nafa K et al (2011) Rebiopsy of lung cancer patients with acquired resistance to EGFR inhibitors and enhanced detection of the T790M mutation using a locked nucleic acid-based assay. Clin Cancer Res 17(5):1169–1180. doi:10.1158/1078-0432.CCR-10-2277 CrossRefPubMedPubMedCentral

62.

Socinski MA, Villaruz LC, Ross J. Understanding mechanisms of resistance in the epithelial growth factor receptor in non-small cell lung cancer and the role of biopsy at progression. Oncologist. 2016

63.

Gerlinger M, Rowan AJ, Horswell S et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366(10):883–892. doi:10.1056/NEJMoa1113205 CrossRefPubMedPubMedCentral

64.

Lindeman NI, Cagle PT, Beasley MB et al (2013) Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Mol Diagn 15(4):415–453. doi:10.1016/j.jmoldx.2013.03.001 CrossRefPubMed

65.

Bordi P, Del Re M, Danesi R, Tiseo M (2015) Circulating DNA in diagnosis and monitoring EGFR gene mutations in advanced non-small cell lung cancer. Transl Lung Cancer Res 4(5):584–597. doi:10.3978/j.issn.2218-6751.2015.08.09 PubMedPubMedCentral

66.

Escriu C, Field JK (2016) Circulating tumour DNA and resistance mechanisms during EGFR inhibitor therapy in lung cancer. J Thorac Dis 8(9):2357–2359. doi:10.21037/jtd.2016.07.96 CrossRefPubMedPubMedCentral

67.

Sacher AG, Paweletz C, Dahlberg SE et al (2016) Prospective validation of rapid plasma genotyping for the detection of EGFR and KRAS mutations in advanced lung cancer. JAMA Oncol. 2(8):1014–1022. doi:10.1001/jamaoncol.2016.0173 CrossRefPubMedPubMedCentral

68.

Oxnard GR, Thress KS, Alden RS et al (2016) Association between plasma genotyping and outcomes of treatment with osimertinib (AZD9291) in advanced non-small-cell lung cancer. J Clin Oncol 34(28):3375–3382. doi:10.1200/JCO.2016.66.7162 CrossRefPubMed

69.

Takahama T, Sakai K, Takeda M et al (2016) Detection of the T790M mutation of EGFR in plasma of advanced non-small cell lung cancer patients with acquired resistance to tyrosine kinase inhibitors (West Japan oncology group 8014LTR study). Oncotarget 7(36):58492–58499. doi:10.18632/oncotarget.11303 CrossRefPubMedPubMedCentral

70.

Ignatiadis M, Lee M, Jeffrey SS (2015) Circulating tumor cells and circulating tumor DNA: challenges and opportunities on the path to clinical utility. Clin Cancer Res 21(21):4786–4800. doi:10.1158/1078-0432.CCR-14-1190 CrossRefPubMed

71.

Braun DA, Burke KP, Van Allen EM (2016) Genomic approaches to understanding response and resistance to immunotherapy. Clin Cancer Res 22(23):5642–5650CrossRefPubMedPubMedCentral

72.

Ribas A, Hamid O, Daud A et al (2016) Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA 315(15):1600–1609. doi:10.1001/jama.2016.4059 CrossRefPubMed

73.

Parsa AT, Waldron JS, Panner A et al (2007) Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med 13(1):84–88CrossRefPubMed

74.

Peng W, Chen JQ, Liu C et al (2016) Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov. 6(2):202–216. doi:10.1158/2159-8290.CD-15-0283 CrossRefPubMed

75.

Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N (2015) Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell 160(1–2):48–61. doi:10.1016/j.cell.2014.12.033 CrossRefPubMedPubMedCentral

76.

Zaretsky JM, Garcia-Diaz A, Shin DS et al (2016) Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med 375(9):819–829. doi:10.1056/NEJMoa1604958 CrossRefPubMedPubMedCentral

77.

Suda K, Murakami I, Sakai K et al (2015) Small cell lung cancer transformation and T790M mutation: complimentary roles in acquired resistance to kinase inhibitors in lung cancer. Sci Rep 5:14447. doi:10.1038/srep14447 CrossRefPubMedPubMedCentral

78.

Janne PA, Yang JC, Kim DW et al (2015) AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med 372(18):1689–1699. doi:10.1056/NEJMoa1411817 CrossRefPubMed

79.

Mok TS, Wu YL, Ahn MJ et al (2016) Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. doi:10.1056/NEJMoa1612674 PubMed

80.

Niederst MJ, Hu H, Mulvey HE et al (2015) The allelic context of the C797S mutation acquired upon treatment with third-generation EGFR inhibitors impacts sensitivity to subsequent treatment strategies. Clin Cancer Res 21(17):3924–3933. doi:10.1158/1078-0432.CCR-15-0560 CrossRefPubMedPubMedCentral

81.

Ercan D, Choi HG, Yun CH et al (2015) EGFR mutations and resistance to irreversible pyrimidine-based EGFR inhibitors. Clin Cancer Res 21(17):3913–3923. doi:10.1158/1078-0432.CCR-14-2789 CrossRefPubMedPubMedCentral

82.

Yu HA, Tian SK, Drilon AE et al (2015) Acquired resistance of EGFR-mutant lung cancer to a T790M-specific EGFR inhibitor: emergence of a third mutation (C797S) in the EGFR tyrosine kinase domain. JAMA Oncol 1(7):982–984. doi:10.1001/jamaoncol.2015.1066 CrossRefPubMedPubMedCentral

83.

Ortiz-Cuaran S, Scheffler M, Plenker D et al (2016) Heterogeneous mechanisms of primary and acquired resistance to third-generation EGFR inhibitors. Clin Cancer Res 22(19):4837–4847CrossRefPubMed

84.

Jia Y, Yun CH, Park E et al (2016) Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. Nature 534(7605):129–132. doi:10.1038/nature17960 CrossRefPubMedPubMedCentral

85.

Janjigian YY, Smit EF, Groen HJ et al (2014) Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov 4(9):1036–1045. doi:10.1158/2159-8290.CD-14-0326 CrossRefPubMedPubMedCentral

86.

Courtin A, Smyth T, Hearn K et al (2016) Emergence of resistance to tyrosine kinase inhibitors in non-small-cell lung cancer can be delayed by an upfront combination with the HSP90 inhibitor onalespib. Br J Cancer 115(9):1069–1077. doi:10.1038/bjc.2016.294 CrossRefPubMed

Titel: Molecular mechanisms of therapy resistance in solid tumors: chasing “moving” targets
verfasst von: Laura J. Tafe
Publikationsdatum: 10.03.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Virchows Archiv / Ausgabe 2/2017
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-017-2101-7

Live-Webinar "Chronische Unterbauch- und Viszeralschmerzen in der Praxis managen"

Springer Medizin

Molecular mechanisms of therapy resistance in solid tumors: chasing “moving” targets

Abstract

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Live-Webinar "Chronische Unterbauch- und Viszeralschmerzen in der Praxis managen"

Springer Medizin

Abstract

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