nach oben

Cancer Chemotherapy and Pharmacology

Erschienen in:

01.12.2015 | Review Article

Targeted therapy in cancer

verfasst von: Apostolia-Maria Tsimberidou

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 6/2015

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To describe the emergence of targeted therapies that have led to significant breakthroughs in cancer therapy and completed or ongoing clinical trials of novel agents for the treatment of patients with advanced cancer.

Methods

The literature was systematically reviewed, based on clinical experience and the use of technologies that improved our understanding of carcinogenesis.

Results

Genomics and model systems have enabled the validation of novel therapeutic strategies. Tumor molecular profiling has enabled the reclassification of cancer and elucidated some mechanisms of disease progression or resistance to treatment, the heterogeneity between primary and metastatic tumors, and the dynamic changes of tumor molecular profiling over time. Despite the notable technologic advances, there is a gap between the plethora of preclinical data and the lack of effective therapies, which is attributed to suboptimal drug development for “driver” alterations of human cancer, the high cost of clinical trials and available drugs, and limited access of patients to clinical trials. Bioinformatic analyses of complex data to characterize tumor biology, function, and the dynamic tumor changes in time and space may improve cancer diagnosis. The application of discoveries in cancer biology in clinic holds the promise to improve the clinical outcomes in a large scale of patients with cancer. Increased harmonization between discoveries, policies, and practices will expedite the development of anticancer drugs and will accelerate the implementation of precision medicine.

Conclusions

Combinations of targeted, immunomodulating, antiangiogenic, or chemotherapeutic agents are in clinical development. Innovative adaptive study design is used to expedite effective drug development.

Tsimberidou AM, Iskander NG, Hong DS, Wheler JJ, Falchook GS, Fu S, Piha-Paul S, Naing A, Janku F, Luthra R, Ye Y, Wen S, Berry D, Kurzrock R (2012) Personalized medicine in a phase I clinical trials program: the MD Anderson Cancer Center initiative. Clin Cancer Res Off J Am Assoc Cancer Res 18(22):6373–6383. doi:10.1158/1078-0432.CCR-12-1627 CrossRef

Von Hoff DD, Stephenson JJ Jr, Rosen P, Loesch DM, Borad MJ, Anthony S, Jameson G, Brown S, Cantafio N, Richards DA, Fitch TR, Wasserman E, Fernandez C, Green S, Sutherland W, Bittner M, Alarcon A, Mallery D, Penny R (2010) Pilot study using molecular profiling of patients’ tumors to find potential targets and select treatments for their refractory cancers. J Clin Oncol Off J Am Soc Clin Oncol 28(33):4877–4883. doi:10.1200/JCO.2009.26.5983 CrossRef

Tsimberidou AM, Eggermont AM, Schilsky RL (2014) Precision cancer medicine: the future is now, only better. Am Soc Clin Oncol Educ Book 34:61–69. doi:10.14694/EdBook_AM.2014.34.6100114000061 CrossRef

Tidyman WE, Rauen KA (2009) The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation. Curr Opin Genet Dev 19(3):230–236. doi:10.1016/j.gde.2009.04.001 PubMedCentralCrossRefPubMed

Roberts PJ, Der CJ (2007) Targeting the Raf–MEK–ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26(22):3291–3310. doi:10.1038/sj.onc.1210422 CrossRefPubMed

Dong J, Phelps RG, Qiao R, Yao S, Benard O, Ronai Z, Aaronson SA (2003) BRAF oncogenic mutations correlate with progression rather than initiation of human melanoma. Cancer Res 63(14):3883–3885PubMed

Poynter JN, Elder JT, Fullen DR, Nair RP, Soengas MS, Johnson TM, Redman B, Thomas NE, Gruber SB (2006) BRAF and NRAS mutations in melanoma and melanocytic nevi. Melanoma Res 16(4):267–273. doi:10.1097/01.cmr.0000222600.73179.f3 CrossRefPubMed

Griewank KG, Westekemper H, Murali R, Mach M, Schilling B, Wiesner T, Schimming T, Livingstone E, Sucker A, Grabellus F, Metz C, Susskind D, Hillen U, Speicher MR, Woodman SE, Steuhl KP, Schadendorf D (2013) Conjunctival melanomas harbor BRAF and NRAS mutations and copy number changes similar to cutaneous and mucosal melanomas. Clin Cancer Res Off J Am Assoc Cancer Res 19(12):3143–3152. doi:10.1158/1078-0432.CCR-13-0163 CrossRef

Curtin JA, Busam K, Pinkel D, Bastian BC (2006) Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol Off J Am Soc Clin Oncol 24(26):4340–4346. doi:10.1200/JCO.2006.06.2984 CrossRef

10.

Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, Obenauf AC, Wackernagel W, Green G, Bouvier N, Sozen MM, Baimukanova G, Roy R, Heguy A, Dolgalev I, Khanin R, Busam K, Speicher MR, O’Brien J, Bastian BC (2010) Mutations in GNA11 in uveal melanoma. N Engl J Med 363(23):2191–2199. doi:10.1056/NEJMoa1000584 PubMedCentralCrossRefPubMed

11.

Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O’Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364(26):2507–2516. doi:10.1056/NEJMoa1103782 PubMedCentralCrossRefPubMed

12.

Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, Rutkowski P, Blank CU, Miller WH Jr, Kaempgen E, Martin-Algarra S, Karaszewska B, Mauch C, Chiarion-Sileni V, Martin AM, Swann S, Haney P, Mirakhur B, Guckert ME, Goodman V, Chapman PB (2012) Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 380(9839):358–365. doi:10.1016/S0140-6736(12)60868-X CrossRefPubMed

13.

Rochet NM, Kottschade LA, Markovic SN (2011) Vemurafenib for melanoma metastases to the brain. N Engl J Med 365(25):2439–2441. doi:10.1056/NEJMc1111672 CrossRefPubMed

14.

Long GV, Trefzer U, Davies MA, Kefford RF, Ascierto PA, Chapman PB, Puzanov I, Hauschild A, Robert C, Algazi A, Mortier L, Tawbi H, Wilhelm T, Zimmer L, Switzky J, Swann S, Martin AM, Guckert M, Goodman V, Streit M, Kirkwood JM, Schadendorf D (2012) Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol 13(11):1087–1095. doi:10.1016/S1470-2045(12)70431-X CrossRefPubMed

15.

Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, Demidov LV, Hassel JC, Rutkowski P, Mohr P, Dummer R, Trefzer U, Larkin JM, Utikal J, Dreno B, Nyakas M, Middleton MR, Becker JC, Casey M, Sherman LJ, Wu FS, Ouellet D, Martin AM, Patel K, Schadendorf D, Group MS (2012) Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med 367(2):107–114. doi:10.1056/NEJMoa1203421 CrossRefPubMed

16.

Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J, Hamid O, Schuchter L, Cebon J, Ibrahim N, Kudchadkar R, Burris HA 3rd, Falchook G, Algazi A, Lewis K, Long GV, Puzanov I, Lebowitz P, Singh A, Little S, Sun P, Allred A, Ouellet D, Kim KB, Patel K, Weber J (2012) Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med 367(18):1694–1703. doi:10.1056/NEJMoa1210093 PubMedCentralCrossRefPubMed

17.

Robert C, Dummer R, Gutzmer R, Lorigan P, Kim KB, Nyakas M, Arance A, Liszkay G, Schadendorf D, Cantarini M, Spencer S, Middleton MR (2013) Selumetinib plus dacarbazine versus placebo plus dacarbazine as first-line treatment for BRAF-mutant metastatic melanoma: a phase 2 double-blind randomised study. Lancet Oncol 14(8):733–740. doi:10.1016/S1470-2045(13)70237-7 CrossRefPubMed

18.

Brugger W, Triller N, Blasinska-Morawiec M, Curescu S, Sakalauskas R, Manikhas GM, Mazieres J, Whittom R, Ward C, Mayne K, Trunzer K, Cappuzzo F (2011) Prospective molecular marker analyses of EGFR and KRAS from a randomized, placebo-controlled study of erlotinib maintenance therapy in advanced non-small-cell lung cancer. J Clin Oncol Off J Am Soc Clin Oncol 29(31):4113–4120. doi:10.1200/JCO.2010.31.8162 CrossRef

19.

Janne PA, Shaw AT, Pereira JR, Jeannin G, Vansteenkiste J, Barrios C, Franke FA, Grinsted L, Zazulina V, Smith P, Smith I, Crino L (2013) Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study. Lancet Oncol 14(1):38–47. doi:10.1016/S1470-2045(12)70489-8 CrossRefPubMed

20.

Blumenschein G Jr, Smit EF, Planchard D, Kim DW, Cadranel J, De Pas T, Dunphy F, Udud K, Ahn MJ, Hanna NH, Kim JH, Mazieres J, Kim SW, Baas P, Rappold E, Redhu S, Puski A, Wu FS, Janne PA (2015) A randomized phase 2 study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small cell lung cancer (NSCLC). Ann Oncol. doi:10.1093/annonc/mdv072

21.

Cantley LC (2002) The phosphoinositide 3-kinase pathway. Science 296(5573):1655–1657. doi:10.1126/science.296.5573.1655 CrossRefPubMed

22.

Zhao L, Vogt PK (2008) Helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms. Proc Natl Acad Sci USA 105(7):2652–2657. doi:10.1073/pnas.0712169105 PubMedCentralCrossRefPubMed

23.

Stephens L, Anderson K, Stokoe D, Erdjument-Bromage H, Painter GF, Holmes AB, Gaffney PR, Reese CB, McCormick F, Tempst P, Coadwell J, Hawkins PT (1998) Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B. Science 279(5351):710–714CrossRefPubMed

24.

Kim JS, Yun HS, Um HD, Park JK, Lee KH, Kang CM, Lee SJ, Hwang SG (2012) Identification of inositol polyphosphate 4-phosphatase type II as a novel tumor resistance biomarker in human laryngeal cancer HEp-2 cells. Cancer Biol Ther 13(13):1307–1318. doi:10.4161/cbt.21788 PubMedCentralCrossRefPubMed

25.

Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, Tokunaga C, Avruch J, Yonezawa K (2002) Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 110(2):177–189CrossRefPubMed

26.

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

27.

Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN (2012) Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 366(6):520–529. doi:10.1056/NEJMoa1109653 CrossRefPubMed

28.

Wagner AJ, Von Hoff DH, Lorusso PM, Tibes R, Mazina KE, Ware JA et al (2009) A first-in-human phase I study to evaluate the pan-PI3K inhibitor GDC-0941 administered QD or BID in patients with advanced solid tumors. In: ASCO annual meeting proceedings. doi:10.1200/JCO.2008.18.5918

29.

Moreno Garcia V, Baird RD, Shah KJ, Basu B, Tunariu N, Blanco M et al (2011) A phase I study evaluating GDC-0941, an oral phosphoinositide-3 kinase (PI3K) inhibitor, in patients with advanced solid tumors or multiple myeloma. In: ASCO annual meeting proceedings, vol 29, p 3021

30.

Von Hoff DD, LoRusso P, Demetri GD, Weiss GJ, Shapiro G, Ramanathan RK et al (2011) A phase I dose-escalation study to evaluate GDC-0941, a pan-PI3K inhibitor, administered QD or BID in patients with advanced or metastatic solid tumors. In: ASCO annual meeting proceedings, vol 29, p 3052. doi:10.1200/JCO.2011.36.5742

31.

Bendell JC, Rodon J, Burris HA, de Jonge M, Verweij J, Birle D, Demanse D, De Buck SS, Ru QC, Peters M, Goldbrunner M, Baselga J (2012) Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. J Clin Oncol Off J Am Soc Clin Oncol 30(3):282–290. doi:10.1200/JCO.2011.36.1360 CrossRef

32.

Arkenau H-T, Jones SF, Kurkjian C, Infante JR, Pant S, Burris HA et al (2012) The PI3K/mTOR inhibitor BEZ235 given twice daily for the treatment of patients (pts) with advanced solid tumors. In: ASCO annual meeting proceedings, vol 30, abstr. 3097

33.

Krop IE, Saura C, Ahnert JR, Becerra C, Britten CD, Isakoff SJ et al (2012) A phase I/IB dose-escalation study of BEZ235 in combination with trastuzumab in patients with PI3-kinase or PTEN altered HER2+ metastatic breast cancer. In: ASCO annual meeting proceedings, vol 30, abstr. 508. doi:10.1200/JCO.2011.40.5902

34.

Carver BS, Chapinski C, Wongvipat J, Hieronymus H, Chen Y, Chandarlapaty S, Arora VK, Le C, Koutcher J, Scher H, Scardino PT, Rosen N, Sawyers CL (2011) Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell 19(5):575–586. doi:10.1016/j.ccr.2011.04.008 PubMedCentralCrossRefPubMed

35.

Reid AH, Attard G, Ambroisine L, Fisher G, Kovacs G, Brewer D, Clark J, Flohr P, Edwards S, Berney DM, Foster CS, Fletcher A, Gerald WL, Moller H, Reuter VE, Scardino PT, Cuzick J, de Bono JS, Cooper CS, Transatlantic Prostate G (2010) Molecular characterisation of ERG, ETV1 and PTEN gene loci identifies patients at low and high risk of death from prostate cancer. Br J Cancer 102(4):678–684. doi:10.1038/sj.bjc.6605554 PubMedCentralCrossRefPubMed

36.

Fritsch C, Huang A, Chatenay-Rivauday C, Schnell C, Reddy A, Liu M, Kauffmann A, Guthy D, Erdmann D, De Pover A, Furet P, Gao H, Ferretti S, Wang Y, Trappe J, Brachmann SM, Maira SM, Wilson C, Boehm M, Garcia-Echeverria C, Chene P, Wiesmann M, Cozens R, Lehar J, Schlegel R, Caravatti G, Hofmann F, Sellers WR (2014) Characterization of the novel and specific PI3Kalpha inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther 13(5):1117–1129. doi:10.1158/1535-7163.MCT-13-0865 CrossRefPubMed

37.

Juric AAG, Burris HA, Juric D et al (2012) Phase I study of BYL719, an alpha-specific PI3K inhibitor, in patients with PIK3CA mutant advanced solid tumors: preliminary efficacy and safety in patients with PIK3CA mutant ER-positive (ER+) metastatic breast cancer (MBC). Cancer Res. 72(24 supplement):P6-10-07

38.

Hoeflich KP, Merchant M, Orr C, Chan J, Den Otter D, Berry L, Kasman I, Koeppen H, Rice K, Yang NY, Engst S, Johnston S, Friedman LS, Belvin M (2012) Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC-0941 triggers robust apoptosis and tumor growth inhibition. Cancer Res 72(1):210–219. doi:10.1158/0008-5472.CAN-11-1515 CrossRefPubMed

39.

Bedard PL, Tabernero J, Janku F, Wainberg ZA, Paz-Ares L, Vansteenkiste J, Van Cutsem E, Perez-Garcia J, Stathis A, Britten CD, Le N, Carter K, Demanse D, Csonka D, Peters M, Zubel A, Nauwelaerts H, Sessa C (2015) A phase Ib dose-escalation study of the oral pan-PI3K inhibitor buparlisib (BKM120) in combination with the oral MEK1/2 inhibitor trametinib (GSK1120212) in patients with selected advanced solid tumors. Clin Cancer Res Off J Am Assoc Cancer Res 21(4):730–738. doi:10.1158/1078-0432.CCR-14-1814 CrossRef

40.

Ciardiello F, Tortora G (2008) EGFR antagonists in cancer treatment. N Engl J Med 358(11):1160–1174. doi:10.1056/NEJMra0707704 CrossRefPubMed

41.

Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, Thongprasert S, Tan EH, Pemberton K, Archer V, Carroll K (2005) Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 366(9496):1527–1537. doi:10.1016/S0140-6736(05)67625-8 CrossRefPubMed

42.

Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabarbara P, Seymour L, National Cancer Instituteof Canada Clinical Trials G (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353(2):123–132. doi:10.1056/NEJMoa050753 CrossRefPubMed

43.

Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA (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/NEJMoa040938NEJMoa040938 CrossRefPubMed

44.

Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304(5676):1497–1500. doi:10.1126/science.1099314 CrossRefPubMed

45.

Sequist LV, Martins RG, Spigel D, Grunberg SM, Spira A, Janne PA, Joshi VA, McCollum D, Evans TL, Muzikansky A, Kuhlmann GL, Han M, Goldberg JS, Settleman J, Iafrate AJ, Engelman JA, Haber DA, Johnson BE, Lynch TJ (2008) First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations. J Clin Oncol 26(15):2442–2449. doi:10.1200/JCO.2007.14.8494 CrossRefPubMed

46.

Cappuzzo F, Ligorio C, Janne PA, Toschi L, Rossi E, Trisolini R, Paioli D, Holmes AJ, Magrini E, Finocchiaro G, Bartolini S, Cancellieri A, Ciardiello F, Patelli M, Crino L, Varella-Garcia M (2007) Prospective study of gefitinib in epidermal growth factor receptor fluorescence in situ hybridization-positive/phospho-Akt-positive or never smoker patients with advanced non-small-cell lung cancer: the ONCOBELL trial. J Clin Oncol 25(16):2248–2255. doi:10.1200/JCO.2006.09.4300 CrossRefPubMed

47.

Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361(10):947–957. doi:10.1056/NEJMoa0810699 CrossRefPubMed

48.

Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M, West Japan Oncology G (2010) Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 11(2):121–128. doi:10.1016/S1470-2045(09)70364-X CrossRefPubMed

49.

Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T, North-East Japan Study G (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362(25):2380–2388. doi:10.1056/NEJMoa0909530 CrossRefPubMed

50.

Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C (2011) Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 12(8):735–742. doi:10.1016/S1470-2045(11)70184-X CrossRefPubMed

51.

Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Munoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L, Spanish Lung Cancer Group in collaboration with Groupe Francais de P-C, Associazione Italiana Oncologia T (2012) Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 13(3):239–246. doi:10.1016/S1470-2045(11)70393-X CrossRefPubMed

52.

Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczesna A, Juhasz E, Esteban E, Molinier O, Brugger W, Melezinek I, Klingelschmitt G, Klughammer B, Giaccone G, Investigators S (2010) Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 11(6):521–529. doi:10.1016/S1470-2045(10)70112-1 CrossRefPubMed

53.

Garassino MC, Martelli O, Broggini M, Farina G, Veronese S, Rulli E, Bianchi F, Bettini A, Longo F, Moscetti L, Tomirotti M, Marabese M, Ganzinelli M, Lauricella C, Labianca R, Floriani I, Giaccone G, Torri V, Scanni A, Marsoni S, Trialists T (2013) Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial. Lancet Oncol 14(10):981–988. doi:10.1016/S1470-2045(13)70310-3 CrossRefPubMed

54.

Altorki NK, O’brien MER, Eberhardt WEE, Richardson FC, Wang J, Foley MA, Horan JD, Shepherd FA, Kelly K (2014) Adjuvant erlotinib (E) versus placebo (P) for completely resected stage IB-IIIA EGFR-positive (IHC/FISH) non-small cell lung cancer (NSCLC): RADIANT results. Int J Radiat Oncol 90:S2–S3CrossRef

55.

Richardson F, Richardson K, Sennello G, Young D, Orlov S, Papai-Szekely Z, Keshavjee S, Kim J, Cerfolio R, Shepherd FA (2009) Biomarker analysis from completely resected NSCLC patients enrolled in an adjuvant erlotinib clinical trial (RADIANT). ASCO Meet Abstr 27(15S):7520

56.

Neal JW, Pennell NA, Govindan R, Lanuti M, Rosovsky RPG, Heist RS, Shaw AT, Temel JS, Muzikansky A, Janne PA, Lynch TJ, Azzoli CG, Sequist LV (2012) The SELECT study: a multicenter phase II trial of adjuvant erlotinib in resected epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). In: ASCO meeting abstracts, vol 30 (15_suppl), p 7010

57.

Sequist LV, Yang JC, Yamamoto N, O’Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M (2013) Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 31(27):3327–3334. doi:10.1200/JCO.2012.44.2806 CrossRefPubMed

58.

Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, Bergethon K, Shaw AT, Gettinger S, Cosper AK, Akhavanfard S, Heist RS, Temel J, Christensen JG, Wain JC, Lynch TJ, Vernovsky K, Mark EJ, Lanuti M, Iafrate AJ, Mino-Kenudson M, Engelman JA (2011) Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 3(75):75ra26. doi:10.1126/scitranslmed.3002003 PubMedCentralCrossRefPubMed

59.

Lynch TJ, Patel T, Dreisbach L, McCleod M, Heim WJ, Hermann RC, Paschold E, Iannotti NO, Dakhil S, Gorton S, Pautret V, Weber MR, Woytowitz D (2010) Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol 28(6):911–917. doi:10.1200/JCO.2009.21.9618 CrossRefPubMed

60.

Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O’Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U, Team FS (2009) Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet 373(9674):1525–1531. doi:10.1016/S0140-6736(09)60569-9 CrossRefPubMed

61.

Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351(4):337–345. doi:10.1056/NEJMoa033025 CrossRefPubMed

62.

Jonker DJ, O’Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357(20):2040–2048. doi:10.1056/NEJMoa071834 CrossRefPubMed

63.

Licitra L, Storkel S, Kerr KM, Van Cutsem E, Pirker R, Hirsch FR, Vermorken JB, von Heydebreck A, Esser R, Celik I, Ciardiello F (2013) Predictive value of epidermal growth factor receptor expression for first-line chemotherapy plus cetuximab in patients with head and neck and colorectal cancer: analysis of data from the EXTREME and CRYSTAL studies. Eur J Cancer 49(6):1161–1168. doi:10.1016/j.ejca.2012.11.018 CrossRefPubMed

64.

Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, Donea S, Ludwig H, Schuch G, Stroh C, Loos AH, Zubel A, Koralewski P (2009) Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 27(5):663–671. doi:10.1200/JCO.2008.20.8397 CrossRefPubMed

65.

Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Tian Y, Xu F, Sidhu R (2014) Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol 25(7):1346–1355. doi:10.1093/annonc/mdu141 CrossRefPubMed

66.

Price TJ, Peeters M, Kim TW, Li J, Cascinu S, Ruff P, Suresh AS, Thomas A, Tjulandin S, Zhang K, Murugappan S, Sidhu R (2014) Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol 15(6):569–579. doi:10.1016/S1470-2045(14)70118-4 CrossRefPubMed

67.

Andersson J, Bumming P, Meis-Kindblom JM, Sihto H, Nupponen N, Joensuu H, Oden A, Gustavsson B, Kindblom LG, Nilsson B (2006) Gastrointestinal stromal tumors with KIT exon 11 deletions are associated with poor prognosis. Gastroenterology 130(6):1573–1581. doi:10.1053/j.gastro.2006.01.043 CrossRefPubMed

68.

Corless CL, Heinrich MC (2008) Molecular pathobiology of gastrointestinal stromal sarcomas. Annu Rev Pathol 3:557–586. doi:10.1146/annurev.pathmechdis.3.121806.151538 CrossRefPubMed

69.

Patel S (2013) Long-term efficacy of imatinib for treatment of metastatic GIST. Cancer Chemother Pharmacol 72(2):277–286. doi:10.1007/s00280-013-2135-8 CrossRefPubMed

70.

Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen CJ, Van den Abbeele AD, Druker BJ, Kiese B, Eisenberg B, Roberts PJ, Singer S, Fletcher CD, Silberman S, Dimitrijevic S, Fletcher JA (2003) Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 21(23):4342–4349. doi:10.1200/JCO.2003.04.190 CrossRefPubMed

71.

Corless CL, Barnett CM, Heinrich MC (2011) Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer 11(12):865–878. doi:10.1038/nrc3143 PubMed

72.

Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG (2006) Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368(9544):1329–1338. doi:10.1016/S0140-6736(06)69446-4 CrossRefPubMed

73.

Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, Hohenberger P, Leahy M, von Mehren M, Joensuu H, Badalamenti G, Blackstein M, Le Cesne A, Schoffski P, Maki RG, Bauer S, Nguyen BB, Xu J, Nishida T, Chung J, Kappeler C, Kuss I, Laurent D, Casali PG, Investigators Gs (2013) Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381(9863):295–302. doi:10.1016/S0140-6736(12)61857-1 CrossRefPubMed

74.

Reichardt P, Blay JY, Gelderblom H, Schlemmer M, Demetri GD, Bui-Nguyen B, McArthur GA, Yazji S, Hsu Y, Galetic I, Rutkowski P (2012) Phase III study of nilotinib versus best supportive care with or without a TKI in patients with gastrointestinal stromal tumors resistant to or intolerant of imatinib and sunitinib. Ann Oncol 23(7):1680–1687. doi:10.1093/annonc/mdr598 CrossRefPubMed

75.

Guo J, Si L, Kong Y, Flaherty KT, Xu X, Zhu Y, Corless CL, Li L, Li H, Sheng X, Cui C, Chi Z, Li S, Han M, Mao L, Lin X, Du N, Zhang X, Li J, Wang B, Qin S (2011) Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification. J Clin Oncol 29(21):2904–2909. doi:10.1200/JCO.2010.33.9275 CrossRefPubMed

76.

Minor DR, Kashani-Sabet M, Garrido M, O’Day SJ, Hamid O, Bastian BC (2012) Sunitinib therapy for melanoma patients with KIT mutations. Clin Cancer Res 18(5):1457–1463. doi:10.1158/1078-0432.CCR-11-1987 CrossRefPubMed

77.

Cho JH, Kim KM, Kwon M, Kim JH, Lee J (2012) Nilotinib in patients with metastatic melanoma harboring KIT gene aberration. Invest New Drugs 30(5):2008–2014. doi:10.1007/s10637-011-9763-9 CrossRefPubMed

78.

Verstovsek S, Tefferi A, Cortes J, O’Brien S, Garcia-Manero G, Pardanani A, Akin C, Faderl S, Manshouri T, Thomas D, Kantarjian H (2008) Phase II study of dasatinib in Philadelphia chromosome-negative acute and chronic myeloid diseases, including systemic mastocytosis. Clin Cancer Res 14(12):3906–3915. doi:10.1158/1078-0432.CCR-08-0366 CrossRefPubMed

79.

Jeselsohn R, Yelensky R, Buchwalter G, Frampton G, Meric-Bernstam F, Gonzalez-Angulo AM, Ferrer-Lozano J, Perez-Fidalgo JA, Cristofanilli M, Gomez H, Arteaga CL, Giltnane J, Balko JM, Cronin MT, Jarosz M, Sun J, Hawryluk M, Lipson D, Otto G, Ross JS, Dvir A, Soussan-Gutman L, Wolf I, Rubinek T, Gilmore L, Schnitt S, Come SE, Pusztai L, Stephens P, Brown M, Miller VA (2014) Emergence of constitutively active estrogen receptor-alpha mutations in pretreated advanced estrogen receptor-positive breast cancer. Clin Cancer Res 20(7):1757–1767. doi:10.1158/1078-0432.CCR-13-2332 PubMedCentralCrossRefPubMed

80.

Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182CrossRefPubMed

81.

Mustacchi G, Biganzoli L, Pronzato P, Montemurro F, Dambrosio M, Minelli M, Molteni L, Scaltriti L (2015) HER2-positive metastatic breast cancer: a changing scenario. Crit Rev Oncol/Hematol. doi:10.1016/j.critrevonc.2015.02.002

82.

Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, Carmichael J (2010) Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet 376(9737):235–244. doi:10.1016/S0140-6736(10)60892-6 CrossRefPubMed

83.

Di Renzo MF, Olivero M, Giacomini A, Porte H, Chastre E, Mirossay L, Nordlinger B, Bretti S, Bottardi S, Giordano S et al (1995) Overexpression and amplification of the met/HGF receptor gene during the progression of colorectal cancer. Clin Cancer Res 1(2):147–154PubMed

84.

Di Renzo MF, Olivero M, Martone T, Maffe A, Maggiora P, Stefani AD, Valente G, Giordano S, Cortesina G, Comoglio PM (2000) Somatic mutations of the MET oncogene are selected during metastatic spread of human HNSC carcinomas. Oncogene 19(12):1547–1555. doi:10.1038/sj.onc.1203455 CrossRefPubMed

85.

Boon EM, van der Neut R, van de Wetering M, Clevers H, Pals ST (2002) Wnt signaling regulates expression of the receptor tyrosine kinase met in colorectal cancer. Cancer Res 62(18):5126–5128PubMed

86.

Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, Lindeman N, Gale CM, Zhao X, Christensen J, Kosaka T, Holmes AJ, Rogers AM, Cappuzzo F, Mok T, Lee C, Johnson BE, Cantley LC, Janne PA (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316(5827):1039–1043. doi:10.1126/science.1141478 CrossRefPubMed

87.

Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L, Chitale D, Motoi N, Szoke J, Broderick S, Balak M, Chang WC, Yu CJ, Gazdar A, Pass H, Rusch V, Gerald W, Huang SF, Yang PC, Miller V, Ladanyi M, Yang CH, Pao W (2007) MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci USA 104(52):20932–20937. doi:10.1073/pnas.0710370104 PubMedCentralCrossRefPubMed

88.

Shojaei F, Lee JH, Simmons BH, Wong A, Esparza CO, Plumlee PA, Feng J, Stewart AE, Hu-Lowe DD, Christensen JG (2010) HGF/c-Met acts as an alternative angiogenic pathway in sunitinib-resistant tumors. Cancer Res 70(24):10090–10100. doi:10.1158/0008-5472.CAN-10-0489 CrossRefPubMed

89.

Shaw AT, Kim DW, Nakagawa K, Seto T, Crino L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O’Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Janne PA (2013) Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 368(25):2385–2394. doi:10.1056/NEJMoa1214886 CrossRefPubMed

90.

Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Gainor J, Engelman JA, Shapiro GI, Costa DB, Ou SH, Butaney M, Salgia R, Maki RG, Varella-Garcia M, Doebele RC, Bang YJ, Kulig K, Selaru P, Tang Y, Wilner KD, Kwak EL, Clark JW, Iafrate AJ, Camidge DR (2011) Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol 12(11):1004–1012. doi:10.1016/S1470-2045(11)70232-7 PubMedCentralCrossRefPubMed

91.

Shaw AT, Mehra R, Kim D-W et al (2013) Clinical activity of the ALK inhibitor LDK378 in advanced, ALK-positive NSCLC. In: ASCO meeting abstracts, vol 31, p 8010

92.

Socinski MA, Goldman J, El-Hariry I, Koczywas M, Vukovic V, Horn L, Paschold E, Salgia R, West H, Sequist LV, Bonomi P, Brahmer J, Chen LC, Sandler A, Belani CP, Webb T, Harper H, Huberman M, Ramalingam S, Wong KK, Teofilovici F, Guo W, Shapiro GI (2013) A multicenter phase II study of ganetespib monotherapy in patients with genotypically defined advanced non-small cell lung cancer. Clin Cancer Res 19(11):3068–3077. doi:10.1158/1078-0432.CCR-12-3381 CrossRefPubMed

93.

Greenwald I (1994) Structure/function studies of lin-12/Notch proteins. Curr Opin Genet Dev 4(4):556–562CrossRefPubMed

94.

Rugo HS, Olopade O, DeMichele A, van ‘t Veer L, Buxton MB, Hylton N, Yee D, Chien AJ, Wallace A, PI’s I-SS, Lyandres J, Davis S, Sanil A, Berry D, Esserman L (2013) Veliparib/carboplatin plus standard neoadjuvant therapy for high-risk breast cancer: first efficacy results from the I-SPY 2 TRIAL. In: 36th Annual San Antonio breast cancer symposium, Abstract S5-02

95.

Chang J, Liu X, Wang S, Zhang Z, Wu Z, Zhang X, Li J (2014) Prognostic value of FGFR gene amplification in patients with different types of cancer: a systematic review and meta-analysis. PLoS One 9(8):e105524. doi:10.1371/journal.pone.0105524 PubMedCentralCrossRefPubMed

96.

Powell MA, Sill MW, Goodfellow PJ, Benbrook DM, Lankes HA, Leslie KK, Jeske Y, Mannel RS, Spillman MA, Lee PS, Hoffman JS, McMeekin DS, Pollock PM (2014) A phase II trial of brivanib in recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study. Gynecol Oncol 135(1):38–43. doi:10.1016/j.ygyno.2014.07.083 PubMedCentralCrossRefPubMed

97.

Escudier B, Grunwald V, Ravaud A, Ou YC, Castellano D, Lin CC, Gschwend JE, Harzstark A, Beall S, Pirotta N, Squires M, Shi M, Angevin E (2014) Phase II results of Dovitinib (TKI258) in patients with metastatic renal cell cancer. Clin Cancer Res 20(11):3012–3022. doi:10.1158/1078-0432.CCR-13-3006 CrossRefPubMed

98.

Yee D (2012) Insulin-like growth factor receptor inhibitors: baby or the bathwater? J Natl Cancer Inst 104(13):975–981. doi:10.1093/jnci/djs258 PubMedCentralCrossRefPubMed

99.

Tsimberidou AM, Ringborg U, Schilsky RL (2013) Strategies to overcome clinical, regulatory, and financial challenges in the implementation of personalized medicine. Am Soc Clin Oncol Educ Book. doi:10.1200/EdBook_AM.2013.33.118 PubMed

100.

Tsimberidou AM, Wen S, Hong DS, Wheler JJ, Falchook GS, Fu S, Piha-Paul S, Naing A, Janku F, Aldape K, Ye Y, Kurzrock R, Berry D (2014) Personalized medicine for patients with advanced cancer in the phase I program at MD Anderson: validation and landmark analyses. Clin Cancer Res 20(18):4827–4836. doi:10.1158/1078-0432.CCR-14-0603 PubMedCentralCrossRefPubMed

Titel: Targeted therapy in cancer
verfasst von: Apostolia-Maria Tsimberidou
Publikationsdatum: 01.12.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 6/2015
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-015-2861-1

Neu im Fachgebiet Onkologie

Bessere Prognose mit links- statt rechtsseitigem Kolon-Ca.

06.05.2024 Kolonkarzinom Nachrichten

Menschen mit linksseitigem Kolonkarzinom leben im Mittel zweieinhalb Jahre länger als solche mit rechtsseitigem Tumor. Auch aktuell ist das Sterberisiko bei linksseitigen Tumoren US-Daten zufolge etwa um 11% geringer als bei rechtsseitigen.

Nodal-negativ nach neoadjuvanter Chemo: Axilladissektion verzichtbar?

03.05.2024 Mammakarzinom Nachrichten

Wenn bei Mammakarzinomen durch eine neoadjuvante Chemotherapie ein Downstaging von nodal-positiv zu nodal-negativ gelingt, scheint es auch ohne Axilladissektion nur selten zu axillären Rezidiven zu kommen.

Wo hapert es noch bei der Umsetzung der POMGAT-Leitlinie?

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Bestrahlung nach Prostatektomie: mehr Schaden als Nutzen?

02.05.2024 Prostatakarzinom Nachrichten

Eine adjuvante Radiotherapie nach radikaler Prostata-Op. bringt den Betroffenen wahrscheinlich keinen Vorteil. Im Gegenteil: Durch die Bestrahlung steigt offenbar das Risiko für Harn- und Stuhlinkontinenz.

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

Springer Medizin

Targeted therapy in cancer

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Onkologie

Bessere Prognose mit links- statt rechtsseitigem Kolon-Ca.

Nodal-negativ nach neoadjuvanter Chemo: Axilladissektion verzichtbar?

Wo hapert es noch bei der Umsetzung der POMGAT-Leitlinie?

Bestrahlung nach Prostatektomie: mehr Schaden als Nutzen?

Update Onkologie

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

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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

Weitere Artikel der Ausgabe 6/2015

Low-dose capecitabine plus trastuzumab as first-line treatment in patients 75 years of age or older with HER2-positive advanced gastric cancer: a pilot study

A phase 1 study of lenvatinib, multiple receptor tyrosine kinase inhibitor, in Japanese patients with advanced solid tumors

Evodiamine inhibits the migration and invasion of nasopharyngeal carcinoma cells in vitro via repressing MMP-2 expression

Phase 1a/1b and pharmacogenetic study of docetaxel, oxaliplatin and capecitabine in patients with advanced cancer of the stomach or the gastroesophageal junction

Pharmacokinetic and pharmacodynamic study of tariquidar (XR9576), a P-glycoprotein inhibitor, in combination with doxorubicin, vinorelbine, or docetaxel in children and adolescents with refractory solid tumors

Oxygen carrier YQ23 can enhance the chemotherapeutic drug responses of chemoresistant esophageal tumor xenografts

Neu im Fachgebiet Onkologie

Bessere Prognose mit links- statt rechtsseitigem Kolon-Ca.

Nodal-negativ nach neoadjuvanter Chemo: Axilladissektion verzichtbar?

Wo hapert es noch bei der Umsetzung der POMGAT-Leitlinie?

Bestrahlung nach Prostatektomie: mehr Schaden als Nutzen?

Update Onkologie