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L. Müllauer
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MA17 - Genetic Drivers (ID 409)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Biology/Pathology
- Presentations: 1
- Moderators:M. Satouchi, G.R. Simon
- Coordinates: 12/07/2016, 14:20 - 15:50, Lehar 1-2
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MA17.08 - Discussant for MA17.05, MA17.06, MA17.07 (ID 7049)
15:08 - 15:20 | Author(s): L. Müllauer
- Abstract
- Presentation
Abstract not provided
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MTE23 - Biomarker Characterization: Challenges and Perspectives (Ticketed Session) (ID 316)
- Event: WCLC 2016
- Type: Meet the Expert Session (Ticketed Session)
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 07:30 - 08:30, Schubert 3
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MTE23.01 - Biomarker Characterization: Challenges and Perspectives (ID 6580)
07:30 - 08:00 | Author(s): L. Müllauer
- Abstract
- Presentation
Abstract:
The treatment of lung adenocarcinomas has improved with the identification of driver gene mutations and the development of drugs tackling the altered driver gene proteins [1]. The interrogation of EGFR mutations as well as ALK and ROS1 translocations is nowadays part of the routine diagnostic workup of lung adenocarcinomas. Further therapies aiming at mutations in driver genes like RET, HER2, BRAF and MET are emerging. The main techniques currently employed in molecular pathology laboratories for mutation detection are mutation specific PCR, conventional capillary (Sanger) sequencing and next generation sequencing (NGS) [2]. The basic principles of these methods, advantages and disadvantages with a special emphasis on NGS and its potency for cancer diagnostics will be discussed. Recently the detection of driver gene mutations in DNA that is derived from cancer cells and released into the blood has become feasible (so-called „liquid biopsy“) [3]. It has already entered routine diagnostics with the detection of the T790M mutation in circulating tumor DNA of primary EGFR mutated lung cancers, that developed resistance to first or second generation tyrosine kinase inhibitors [4]. The verification of a T790M mutation either by liquid biopsy or the analysis of tumor tissue is a prerequisite for therapy of lung adenocarcinomas with third generation tyrosine kinase inhibitors like osimertinib. The principles of liquid biopsy, employed techniques and potential applications will be introduced. The recent advent of cancer immunotherapy that interferes with immune checkpoint molecules like programmed death 1 (PD-1) offers a new treatment for subgroups of lung cancer patients. A biomarker that would predict responsiveness to this expensive therapy is greatly needed. The expression of the PD-1 ligand (PD-L1) by tumor or immune/stromal cells is a potential biomarker, however its utility is heavily debated [5]. The confusion on PD-L1 as a biomarker is partly caused by technical difficulties in the determination of expression, such as the antibody used for immunohistochemistry and the determination of a treshold of expression that correlates with response [6]. A further biomarker that is determined by immunohistochemistry is the expression of EGFR in lung squamous cell carcinoma. A therapy with the recently approved anti-EGFR antibody necitumumab requires the demonstration of EGFR expression by the cancer cells [7]. The methods and pitfalls in PD-1 and EGFR immunohistochemistry will be presented. The requirement for biomarkers increases. This poses a challenge for diagnostics in respect to availabiltity of techniques, infrastructure and budget. Particularly in lung cancer often very little tissue is available, but different assays should be run. To fulfill the increasing demand for a plethora of biomarker analysis multiplexing techniques that simultaneously interrogate a large number of gene mutations, gene fusions, gene amplification and deletions, as well as RNA and protein expression will be needed. An outlook on available and emerging multiplexing techniques will be provided. References 1. The Cancer Genome Atlas Research N (2014) Comprehensive molecular profiling of lung adenocarcinoma. Nature 511 (7511):543-550. doi:10.1038/nature13385 2. Buermans HP, den Dunnen JT (2014) Next generation sequencing technology: Advances and applications. Biochimica et biophysica acta 1842 (10):1932-1941. doi:10.1016/j.bbadis.2014.06.015 3. Diaz LA, Jr., Bardelli A (2014) Liquid biopsies: genotyping circulating tumor DNA. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 32 (6):579-586. doi:10.1200/JCO.2012.45.2011 4. Thress KS, Paweletz CP, Felip E, Cho BC, Stetson D, Dougherty B, Lai Z, Markovets A, Vivancos A, Kuang Y, Ercan D, Matthews SE, Cantarini M, Barrett JC, Janne PA, Oxnard GR (2015) Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med 21 (6):560-562. doi:10.1038/nm.3854 http://www.nature.com/nm/journal/v21/n6/abs/nm.3854.html - supplementary-information 5. Sunshine J, Taube JM (2015) PD-1/PD-L1 inhibitors. Current opinion in pharmacology 23:32-38. doi:10.1016/j.coph.2015.05.011 6. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn M-J, Felip E, Lee J-S, Hellmann MD, Hamid O, Goldman JW, Soria J-C, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L (2015) Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer. New England Journal of Medicine 372 (21):2018-2028. doi:doi:10.1056/NEJMoa1501824 7. Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Balint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA (2015) Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. The Lancet Oncology 16 (7):763-774. doi:10.1016/s1470-2045(15)00021-2
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