DISEASE AREA COORDINATORS

Prof. Dr. Ursula Klingmüller (TLRC), Prof. Dr. Michael Thomas (TLRC)

(Administr. Coordinator: Dr. Birgit Teucher (TLRC))

CONTRIBUTING PARTNER SITES

ARCN, BREATH, CPC-M, TLRC

OVERVIEW

Lung cancer is a high incidence and high mortality disease. The two main lung cancer types are small-cell-lung carcinoma (SCLC; 20-30% of cases) and non-small cell lung carcinoma (NSCLC; 70-80% of cases). Patients presenting with SCLC have a particularly poor prognosis, and almost 40 % of NSCLC-patients present with metastases at time of diagnosis.  Surgery, radiation, chemotherapy, and on a limited scale, targeted treatments —alone or in combination—are used to treat lung cancer. Limited knowledge of which individual molecular markers impact the propagation and spread of the disease impedes the development and use of targeted therapies; hence the treatment success is very variable. Our research focuses on the identification of relevant molecular markers urgently needed to advance matching of targeted treatments to patients, with the ultimate goal of developing personalized therapies to improve patient outcomes. Lung cancer research at the DZL is an interdisciplinary and integrative program exploring clinically well characterized sample sets with epidemiologic, genetic, epigenetic and systems biology approaches.

MAJOR RESEARCH GOALS

  • Knowledge based optimization of an early clinical trial pipeline through validation of treatment efficacy and development of predictive diagnostics and individualized treatment regimens
  • Development of sequential biomaterial acquisition in clinical cohorts including assessment of alterations indicative for tumor progression and therapy resistance
  • Identification of dynamic properties promoting early spread, therapy resistance and recurrence
  • Establishment of biomarkers for lung cancer risk and malignant transition

Lung Cancer:  Selected Publications from DZL Faculty Members Published Since 2010

Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Lu H, Cuillerot JM, Lynch TJ. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol 2013;24:75-83.

Shaw A, Kim DW, Nakawaga K, Seto T, Crino L, Ahn M-J, de Pas T, Besse B, Solomon BJ, Blackhall F, Wu Y-L-, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA. Crizotinib versus Chemotherapy in Advanced ALk-rearranged Lung Cancer. New England Journal of Medicine 2013;in press.

Bachmann J, Raue A, Schilling M, Becker V, Timmer J, Klingmuller U. Predictive mathematical models of cancer signalling pathways. J Intern Med 2012;271:155-165.

Campa D, Muller P, Edler L, Knoefel L, Barale R, Heussel CP, Thomas M, Canzian F, Risch A. A comprehensive study of polymorphisms in ABCB1, ABCC2 and ABCG2 and lung cancer chemotherapy response and prognosis. Int J Cancer 2012;131:2920-2928.

Peifer M, Fernandez-Cuesta L, Sos ML, George J, Seidel D, Kasper LH, Plenker D, Leenders F, Sun R, Zander T, Menon R, Koker M, Dahmen I, Muller C, Di Cerbo V, Schildhaus HU, Altmuller J, Baessmann I, Becker C, de Wilde B, Vandesompele J, Bohm D, Ansen S, Gabler F, Wilkening I, Heynck S, Heuckmann JM, Lu X, Carter SL, Cibulskis K, Banerji S, Getz G, Park KS, Rauh D, Grutter C, Fischer M, Pasqualucci L, Wright G, Wainer Z, Russell P, Petersen I, Chen Y, Stoelben E, Ludwig C, Schnabel P, Hoffmann H, Muley T, Brockmann M, Engel-Riedel W, Muscarella LA, Fazio VM, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman DA, Snijders PJ, Cappuzzo F, Ligorio C, Damiani S, Field J, Solberg S, Brustugun OT, Lund-Iversen M, Sanger J, Clement JH, Soltermann A, Moch H, Weder W, Solomon B, Soria JC, Validire P, Besse B, Brambilla E, Brambilla C, Lantuejoul S, Lorimier P, Schneider PM, Hallek M, Pao W, Meyerson M, Sage J, Shendure J, Schneider R, Buttner R, Wolf J, Nurnberg P, Perner S, Heukamp LC, Brindle PK, Haas S, Thomas RK. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet 2012;44:1104-1110.

Scherf DB, Sarkisyan N, Jacobsson H, Claus R, Bermejo JL, Peil B, Gu L, Muley T, Meister M, Dienemann H, Plass C, Risch A. Epigenetic screen identifies genotype-specific promoter DNA methylation and oncogenic potential of CHRNB4. Oncogene 2012 [Epub ahead of print]

Tian F, Mysliwietz J, Ellwart J, Gamarra F, Huber RM, Bergner A. Effects of the Hedgehog pathway inhibitor GDC-0449 on lung cancer cell lines are mediated by side populations. Clin Exp Med 2012;12:25-30.

Warth A, Muley T, Meister M, Stenzinger A, Thomas M, Schirmacher P, Schnabel PA, Budczies J, Hoffmann H, Weichert W. The novel histologic International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification system of lung adenocarcinoma is a stage-independent predictor of survival. J Clin Oncol 2012;30:1438-1446.

Schultz H, Marwitz S, Baron-Luhr B, Zissel G, Kugler C, Rabe KF, Zabel P, Vollmer E, Gerdes J, Goldmann T. Generation and evaluation of a monoclonal antibody, designated MAdL, as a new specific marker for adenocarcinomas of the lung. Br J Cancer 2011;105:673-681.

Truong T, Hung RJ, Amos CI, Wu X, Bickeboller H, Rosenberger A, Sauter W, Illig T, Wichmann HE, Risch A, Dienemann H, Kaaks R, Yang P, Jiang R, Wiencke JK, Wrensch M, Hansen H, Kelsey KT, Matsuo K, Tajima K, Schwartz AG, Wenzlaff A, Seow A, Ying C, Staratschek-Jox A, Nurnberg P, Stoelben E, Wolf J, Lazarus P, Muscat JE, Gallagher CJ, Zienolddiny S, Haugen A, van der Heijden HF, Kiemeney LA, Isla D, Mayordomo JI, Rafnar T, Stefansson K, Zhang ZF, Chang SC, Kim JH, Hong YC, Duell EJ, Andrew AS, Lejbkowicz F, Rennert G, Muller H, Brenner H, Le Marchand L, Benhamou S, Bouchardy C, Teare MD, Xue X, McLaughlin J, Liu G, McKay JD, Brennan P, Spitz MR. Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium. J Natl Cancer Inst 2010;102:959-971.