Genetic aberrations underlie the malignant transformation of cells. The knowledge of the genetic alterations in a tumor and the thereby perturbed and interacting signaling pathways enables the diagnosis and subclassification of tumors, the identification of potential targets for the development of novel drugs and the stratification of therapies in accordance with the molecular profile of a tumor. The research group "Molecular Tumor Pathology" focuses on the identification and functional characterization of genetic changes in various neoplastic diseases to enable and improve a personalized therapy based on the biology of an individual tumor.
The main objectives of the research group "Molecular Tumor Pathology" are the development and utilization of state of the art molecular tumor diagnostics and the identification of molecular aberrations in tumor cells that can be exploited for the generation of novel therapy concepts and the adjustment of therapy to the molecular and cell biological features of tumor cells.
The "Molecular Tumor Pathology" research group employs a broad spectrum of molecular biology techniques with an emphasis on next generation sequencing methods. The genetic interrogation of tumors is complemented by functional assays with in vitro drug testing to derive a more comprehensive insight into the biology and behaviour of tumor cells and their vulnerability to cancer therapeutics. The main goal is to enable a personalized cancer treatment that integrates genetic analysis and functional in vitro assays for the selection of the best therapy for the individual patient.
The molecular characterization of mucinous lung adenocarcinomas
Mucinous lung adenocarcinoma represents 2-4% of lung adenocarcinomas. This lung carcinoma subtype is genetically less characterized than other more frequent adenocarcinoma variants. We want to elucidate the molecular aberrations in 50 mucinous lung adenocarcinomas by DNA and RNA sequencing with a panel of 300 genes that are frequently altered in human cancers. The aim is to identify recurrently activated signaling pathways that may represent targets for therapy.
PIK3CA mutations in breast cancers
PIK3CA is the catalytic subunit of the phosphatidylinositol 3-kinase (PI3K), a central signaling molecule activated by receptor tyrosine kinases and RAS. Mutated PIK3CA can be inhibited by the drug alpelisib. We investigate the frequency and type of PIK3CA mutations together with estrogen receptor mutations and 50 additional cancer genes in three groups of metastasized breast cancer: a) primary estrogen inhibitor resistant b) secondary estrogen receptor resistant and c) hormone inhibitor sensitive.
Functional genomics for the prediction of drug sensitivity
The identification of gene mutations often cannot predict drug responses. Therefore, we aim to establish in vitro assays with isolated tumor cells kept in short and long term cultures (including organoids) and exposed to various drugs. The results of these cell culture assays shall be combined with the sequencing results to identify drugs with a high likelihood of efficacy for a given tumor.
- Zöchbauer-Müller S, Kaserer B, Prosch H, Cseh A, Solca F, Bauer MJ, Müllauer L. Case Report: Afatinib Treatment in a Patient With NSCLC Harboring a Rare EGFR Exon 20 Mutation. Front Oncol. 2021 Jan 26;10:593852. doi: 10.3389/fonc.2020.593852. eCollection 2020
- Oberndorfer F, Moling S, Hagelkruys LA, Grimm C, Polterauer S, Sturdza A, Aust S, Reinthaller A, Müllauer L, Schwameis R. Risk Reclassification of Patients with Endometrial Cancer Based on Tumor Molecular Profiling: First Real World Data. J Pers Med. 2021 Jan 15;11(1):48. doi: 10.3390/jpm11010048
- Oberndorfer F,Müllauer L. Genomic alterations in thymoma-molecular pathogenesis? J Thorac Dis. 2020 Dec;12(12):7536-7544. doi: 10.21037/jtd.2019.12.52
- Taghizadeh H, Unseld M, Spalt M, Mader RM, Müllauer L, Fuereder T, Raderer M, Sibilia M, Hoda MA, Aust S, Polterauer S, Lamm W, Bartsch R, Preusser M, A KW, Prager GW. Targeted Therapy Recommendations for Therapy Refractory Solid Tumors-Data from the Real-World Precision Medicine Platform MONDTI. J Pers Med. 2020 Oct 23;10(4):E188. doi: 10.3390/jpm10040188.PMID:33114048#
- Taghizadeh H, Müllauer L, Mader RM, Schindl M, Prager GW. Applied precision medicine in metastatic pancreatic ductal adenocarcinoma. Ther Adv Med Oncol. 2020 Jul 10;12:1758835920938611. doi: 10.1177/1758835920938611. eCollection 2020
- Taghizadeh H, Mader RM, Müllauer L, Aust S, Polterauer S, Kölbl H, Seebacher V, Grimm C, Reinthaller A, Prager GW. Molecular Guided Treatments in Gynecologic Oncology: Analysis of a Real-World Precision Cancer Medicine Platform. Oncologist. 2020 Jul;25(7):e1060-e1069. doi: 10.1634/theoncologist.2019-0904. Epub 2020 May 8
- Taghizadeh H, Müllauer L, Mader R, Prager GW. Applied precision cancer medicine in metastatic biliary tract cancer..Hepatol Int. 2020 Mar;14(2):288-295. doi: 10.1007/s12072-020-10020-6. Epub 2020 Feb 25
- Voigt W, Manegold C, Pilz L, Wu YL, Müllauer L, Pirker R, Filipits M, Niklinski J, Petruzelka L, Prosch H. Beyond tissue biopsy: a diagnostic framework to address tumor heterogeneity in lung cancer. Curr Opin Oncol. 2020 Jan;32(1):68-77.doi: 10.1097/CCO.0000000000000598. Review. PubMed PMID: 31714259
- Taghizadeh H, Mader RM, Müllauer L, Fuereder T, Kautzky-Willer A, Prager GW. Outcome of Targeted Therapy Recommendations for Metastatic and Recurrent Head and Neck Cancers. Cancers (Basel). 2020 Nov 15;12(11):3381. doi: 10.3390/cancers12113381
The research group "Molecular Tumor Pathology" is currently funded by:
Roche. Project 1: Characterisation of malignant diseases with FoundationOne Assay (2019-2021)
Novartis. Project 2: Status of PIK3CA mutations from archival primary tumor and matched archival metastatic samples in HR+/HER2- breast cancer from the biobank established (2019-2021)