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SDIRSACR Oncology Insights

could be relevant parameters for monitoring during immunotherapy. In the next step, these and new markers will be
evaluated in the larger cohort at the three different time points.
Conclusions: This comprehensive study could enable us to identify new predictive and pharmacodynamic biomarkers
for immunotherapy at the metabolite level. This offers new opportunities for patient stratification, early detection
of non-responders and side effects, and further understanding of resistance. By using this new innovative and non-
invasive method, we can capture processes in patients without major thresholds.

Acknowledgments and funding: Hiege grant, Promedics grant

L23

Personalized Genomic Analysis for Clinical Insights in Non-Small Cell Lung Cancer

Miodrag Dragoj , Sofija Jovanović Stojanov , Ana Podolski-Renić , Jelena Dinić , Ana Stepanović , Ema Lupšić , Milica
1
1
1
1
1
1
Pajović , Dušica Petrović Rodić , Sofija Glumac , Dragana Marić , Maja Ercegovac , Milica Pešić 1
3,4
1
3,6
3,5
2
1Department of Neurobiology, Institute for Biological Research "Siniša Stanković" – National Institute of the Republic of Serbia,
University of Belgrade, Belgrade, Serbia
2Department of Thoracic Pathology, Clinical Center of Serbia, Service of Pathohistology, University of Belgrade, Belgrade, Serbia
3School of Medicine, University of Belgrade, Dr. Subotića 8, 11000 Belgrade, Serbia.
4Institute of Pathology, School of Medicine, University of Belgrade, Dr. Subotića 1, 11000 Belgrade, Serbia.
5Clinic for Pulmonology, University of Belgrade – Faculty of Medicine, Belgrade, Serbia,
6Clinic for Thoracic Surgery, University of Belgrade – Faculty of Medicine, Belgrade, Serbia
Keywords: Exome Sequencing, Molecular profiling, NSCLC, Patient-Derived Cell Cultures, Personalized Therapy
Background: Non-small cell lung carcinoma (NSCLC) accounts for approximately 85% of all lung cancer cases and
remains the leading cause of cancer-related mortality worldwide [1]. Clinical treatment has improved significantly in
recent years with the introduction of targeted therapies and immune checkpoint inhibitors. Therapeutic decisions are
largely guided by the identification of somatic genetic driver alterations in tumors [2]. However, this approach alone is
often insufficient to capture the complexity of tumor biology and functional response to treatment.
Decreasing sequencing costs and advances in the analysis of sequencing data have opened up the possibility of using
whole-exome sequencing (WES) in the clinic. Applying this approach to genomic profiling enables the identification
of all potential driver mutations, tumor mutational burden, homologous recombination deficiency, mismatch repair
deficiency, copy number alterations, mutational signatures and even germline information for each patient [3]. By
overcoming the limitations of targeted panels, WES facilitates more personalized characterization of tumor biology,
which is important for optimizing precision oncology approaches [4,5]. In parallel, functional testing of the patient-
derived tumor cells in response to drugs offers a direct way of assessing treatment sensitivity [6]. Drug testing on
primary cell cultures, including chemotherapeutics and tyrosine kinase inhibitors (TKIs), enables real-time assessment
of cytotoxicity and treatment sensitivity that can be directly correlated with the underlying genomic landscape [7].
By integrating functional drug response data with WES-based genomic profiling, our approach aims to provide a
potentially comprehensive diagnostic platform for NSCLC. This combined methodology not only identifies clinically
actionable genomic features, but also validates their functional relevance, thus improving predictive power. It also allows
us to identify rare, exceptional responders in unselected patients, which is not possible with current patient selection
strategies. Ultimately, this integrative approach represents a step towards truly personalized cancer diagnostics, where
both the molecular and functional characteristics of the tumor are taken into account in clinical decision-making.
Methodology: Collection of NSCLC tissue samples. Tissue samples from 67 NSCLC patients were collected from the
Clinic for Thoracic Surgery at the University Clinical Center of Serbia with informed consent obtained from the patients
and approved by the Ethics Committee of the University Clinical Center of Serbia (approval reference number 623/4).
Samples were collected during surgery and histopathologically examined to confirm the diagnosis of NSCLC, histologic
grade, stage, necrosis and status of lymph node invasion. Fresh tumor tissue destined for primary cell culture was
placed in sterile tubes containing an antibiotic–antimycotic solution and immediately transported to the research
laboratory for further processing. For WES, paired tumor and corresponding normal tissue samples were frozen in
liquid nitrogen immediately after surgical removal and stored in liquid nitrogen until DNA isolation.
Patent-derived NSCLC cell cultures. Patient-derived NSCLC cell cultures containing both cancer cells and stromal
components were established from freshly collected NSCLC tumor samples. These primary cultures were maintained

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