ICHNO-ECHNO 2022 - Abstract Book

S87

ICHNO-ECHNO 2022

PO-0138 Autophagy as a therapeutic target in head and neck squamous cell carcinoma

S.A. Kandathil 1 , A.L. Lein 1 , A. Scheiflinger 1 , G. Heiduschka 1

1 Medical University of Vienna, Department of Otorhinolaryngology, Vienna, Austria

Purpose or Objective Macroautophagy (hereafter referred to as "autophagy") is an evolutionarily conserved process to eliminate damaged proteins, protein complexes, and organelles in the cell. Therefore, the autophagic machinery facilitates cell survival under stressful circumstances, including tumor cells, which experience metabolic stress. However, the only FDA-approved drug to inhibit autophagy is Hydroxychloroquine (HCQ), but its use is limited due to its low potency and side effects at therapeutically relevant dosages. The objective of this study was to determine whether the novel autophagy inhibitors Lys05 and SBI-0206965 could sensitize more potently established head and neck squamous cell carcinoma (HNSCC) cell lines CAL27 and FaDu to the effects of Cisplatin and radiotherapy than HCQ. Materials and Methods Cell viability and wound healing assay of the HNSCC cell lines CAL27 (tongue) and FaDu (hypopharynx) treated with the autophagy inhibitors Lys05 and SBI-0206965 only and combined with Cisplatin and/or radiotherapy were assessed. Additionally, synergistic or additive antitumor effects of the therapy combinations were assessed. Moreover, the effect on cell viability after treatment was also investigated in 3D spheroids comprised of CAL27 and FaDu grown in ultra-low attachment plates. Results Lys05 and SBI-0206965 showed an IC50 at 4uM, whereas the IC50 of HCQ varied between 20 to 60uM depending on the cell line. Cell migration was inhibited with novel drugs at doses ranging between 1 to 3uM. In comparison, HCQ could only inhibit cell migration at dosages between 10 and 50uM. Furthermore, chemotherapy - comprised of autophagy inhibition and Cisplatin - and radiotherapy combined showed a significant decrease in cell viability in 2D and 3D cell culture. Conclusion Chemically targeting autophagy with specific inhibitors in established HNSCC cell lines shows significant reduction of cell viability and impairment of cancer cell migration. 1 M. Sklodowska-Curie National Research Institute of Oncology, ANALYTICS AND CLINICAL BIOCHEMISTRY DEPARTMENT, Gliwice, Poland; 2 M. Sklodowska-Curie National Research Institute of Oncology, I RADIATION AND CLINICAL ONCOLOGY DEPARTMENT, Gliwice, Poland; 3 M. Sklodowska-Curie National Research Institute of Oncology,, ANALYTICS AND CLINICAL BIOCHEMISTRY DEPARTMENT, Gliwice, Poland; 4 M. Sklodowska-Curie National Research Institute of Oncology, DEPARTMENT OF MEDICAL PHYSICS, Gliwice, Poland Purpose or Objective In patients with HNC anemia is common symptom and usually consist of both components: treatment related anemia and anemia of chronic disease. The disparity between production and elimination of erythrocytes is a direct reason of anemia which is characterized by low levels of circulating red blood cells and hemoglobin (Hb), reduced number of reticulocytes (Ret), inadequate secretion of erythropoietin (Epo) and disturbances in iron metabolism. Although the thorough mechanisms of anemia of chronic disease is not fully understood, it causes tissue hypoxia that increases resistance to radiotherapy. The aim of this study was to assess the clinical utility parameters of the erythrocytic system: reticulocytes (Ret), immature reticulocyte fraction (IRF), the concentration of Epo and sEpoR as a marker of tumor hypoxia. Materials and Methods Between 01/2009 and 08/2013 186 patients with squamous cell cancer of oral cavity (5%), nasopharynx (7%), oropharynx (30%), hypopharynx (10%) and larynx (48%) were treated with radiotherapy alone (40%) or combined with chemotherapy (60%). There were 19%, 33%, 27%, and 21% patients with T1, T2, T3 and T4 tumor stage and 48%, 11%, 29%, and 11% patients with N0, N1, N2 and N3 nodal stage of disease respectively. Epo, sEpoR and parameters of the red blood cell system were estimated in plasma or blood before and immediately after treatment completion. Results Strong negative correlation before treatment has been found in patients with anemia (Hb< 11 g/ml) between Hb levels and Epo (p=.0004), Ret (p=.04) and IFR (p=.0001). Additionally, a negative correlation in patients with anemia has been found between Hb levels and Epo (p=.005) and IRF (p=.0001) after treatment. Significantly longer overall survival (OS) has been found for patients with decreased Epo levels (p=.01) and elevated Hb levels (p=.03) before treatment and elevated IFR (p=.04) after treatment. Also, in the multivariate analysis, pre- and posttreatment Epo levels were an independent prognostic factors for shorter OS (p=.02; p= .004; respectively) Conclusion In patients with HNC, anemia is a chronic disease which may stimulate erythropoiesis. IFR may indicate increased and ineffective erythropoiesis which correlates with increased risk of death. Pre- and posttreatment Epo are prognostic determinants of OS in this group of patients. PO-0139 Prognostic value of erythropoietin, hematological parameters in patients with head and neck cancer J. Mrochem-Kwarciak 1 , T. Rutkowski 2 , A. Wygoda 2 , N. Amrogowicz 2 , R. Deja 3 , A. Chmura 1 , Ł . Boguszewicz 4 , K. Sk ł adowski 2