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Background: Personalized therapy in lung cancer has improved folloing the introduction of EGFR tyrosine kinase inhibitors. Hoever, virtually all patients develop resistance leading to disease relapse and decreased patient survival. With the advances in research, several mechanisms have been identified to be involved in the development of resistance, including activation of ErbB3HER3. HER3 is a key dimerization partner of EGFR and plays an important role in tumorigenesis and cancer progression. As a result, anti-HER3 therapies have been developed and clinical trials ith monoclonal antibodies against HER3 are ongoing in NSCLC in combination ith other therapies x2018;standard of care . The influence of concomitant therapies such as platinum chemotherapy on EGFR-HER3 heterodimerization remains largely unexplored. We hypothesize that in a subgroup of NSCLC patients, cisplatin treatment ill impact on the x2018;dependence of the tumor on HER3, due to its disruptive effect on the EGFR-HER3 dimer interaction. Methods: We developed a protocol for immunostaining and fluorescence lifetime imaging microscopy FLIM of patient-derived exosomes to determine the ability to characterize the EGFR-HER3 dimer from clinical samples of patients ith advanced NSCLC. Blood samples ere collected prior to initiation of chemotherapy cisplatin and 3 eeks after. Biochemical and microscopy analyses ere performed on purified exosomes from the paired serum samples of patients. Results: The presence and degree of the EGFR-HER3 dimer in the serum-derived exosomes of NSCLC patients as variable and as significantly reduced in a proportion of patients folloing treatment ith Cisplatin. These results ere reproduced in cell-line derived exosomes treated under the same conditions. Conclusions: Our observations may have important clinical implications for the use of anti-HER3 monoclonal antibodies in NSCLC patients, ith regard to scheduling of cisplatin treatment. They can also allo the creation of a multivariate predictive model of combining exosomal ErbB receptor activation ith other biomarkers of disease to prospectively predict response to chemotherapy and targeted agents as ell as time to metastatic relapse.,J Clin Oncol 34, 2016 suppl; abstr e23100 ,Publication Only Tumor Biology