| Autor: |
Dinić J; Department of Neurobiology, Institute for Biological Research 'Siniša Stanković'-National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia., Dragoj M; Department of Neurobiology, Institute for Biological Research 'Siniša Stanković'-National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia., Jovanović Stojanov S; Department of Neurobiology, Institute for Biological Research 'Siniša Stanković'-National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia., Stepanović A; Department of Neurobiology, Institute for Biological Research 'Siniša Stanković'-National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia., Lupšić E; Department of Neurobiology, Institute for Biological Research 'Siniša Stanković'-National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia., Pajović M; Department of Neurobiology, Institute for Biological Research 'Siniša Stanković'-National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia., Mohr T; Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria., Glumac S; Institute of Pathology, School of Medicine, University of Belgrade, Dr. Subotića 1, 11000 Belgrade, Serbia.; School of Medicine, University of Belgrade, Dr. Subotića 8, 11000 Belgrade, Serbia., Marić D; School of Medicine, University of Belgrade, Dr. Subotića 8, 11000 Belgrade, Serbia.; Clinic for Pulmonology, University Clinical Center of Serbia, Dr. Koste Todorovića 26, 11000 Belgrade, Serbia., Ercegovac M; School of Medicine, University of Belgrade, Dr. Subotića 8, 11000 Belgrade, Serbia., Podolski-Renić A; Department of Neurobiology, Institute for Biological Research 'Siniša Stanković'-National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia., Pešić M; Department of Neurobiology, Institute for Biological Research 'Siniša Stanković'-National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia. |
| Abstrakt: |
The impact of tyrosine kinase inhibitors (TKIs) on multidrug resistance (MDR) in non-small cell lung carcinoma (NSCLC) is a critical aspect of cancer therapy. While TKIs effectively target specific signaling pathways of cancer cells, they can also act as substrates for ABC transporters, potentially triggering MDR. The aim of our study was to evaluate the response of 17 patient-derived NSCLC cultures to 10 commonly prescribed TKIs and to correlate these responses with patient mutational profiles. Using an ex vivo immunofluorescence assay, we analyzed the expression of the MDR markers ABCB1, ABCC1, and ABCG2, and correlated these data with the genetic profiles of patients for a functional diagnostic approach. NSCLC cultures responded differently to TKIs, with erlotinib showing good efficacy regardless of mutation burden or EGFR status. However, the modulation of MDR mechanisms by erlotinib, such as increased ABCG2 expression, highlights the challenges associated with erlotinib treatment. Other TKIs showed limited efficacy, highlighting the variability of response in NSCLC. Genetic alterations in signaling pathways associated with drug resistance and sensitivity, including TP53 mutations, likely contributed to the variable responses to TKIs. The relationships between ABC transporter expression, gene alterations, and response to TKIs did not show consistent patterns. Our results suggest that in addition to mutational status, performing functional sensitivity screening is critical for identifying appropriate treatment strategies with TKIs. These results underscore the importance of considering drug sensitivity, off-target effects, MDR risks, and patient-specific genetic profiles when optimizing NSCLC treatment and highlight the potential for personalized approaches, especially in early stages. |
