American Association for Cancer Research
15357163mct170667-sup-186262_2_supp_4435628_p0k20x.pdf (470.04 kB)

Supplementary Figures 1-9 from JAK2 Inhibitor SAR302503 Abrogates PD-L1 Expression and Targets Therapy-Resistant Non–small Cell Lung Cancers

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journal contribution
posted on 2023-04-03, 15:03 authored by Sean P. Pitroda, Melinda E. Stack, Gene-Fu Liu, Sui-Sui Song, Lucy Chen, Hua Liang, Akash D. Parekh, Xiaona Huang, Paul Roach, Mitchell C. Posner, Ralph R. Weichselbaum, Nikolai N. Khodarev

Supplemental Figure S1. Comparison of clonogenic survival fractions of various cancer cell lines after treatment with SAR302503 and Ruxolitinib. Supplemental Figure S2. KRAS mutation by treatment sensitivities in NSCLC cell lines. Supplementary Figure S3. The response of NCIH1944 xenografts to ionizing radiation. Supplemental Figure S4. Top-ranked pathways in SAR sensitive NSCLC cell lines. Supplemental Figure S5. Cancer growth and proliferation gene network in SAR-sensitive NSCLC. Supplemental Figure S6. ROC analysis of SAR sensitivity by TSP-IRDS scores. Supplemental Figure S7. Distribution of TSP-IRDS scores in clinical NSCLCs. Supplemental Figure S8. TSP-IRDS predicts survival in clinical NSCLC. Supplemental Figure S9. TSP-IRDS scores predict the benefit of adjuvant cisplatin-based chemotherapy in clinical NSCLC. Supplementary Figure and Table Legends



Cleveland Clinic

Cancer Research Foundation

Ludwig Center for Metastasis Research

Ludwig Foundation for Cancer Research

Prostate Cancer Research Foundation

Vincent Foglia



Lung cancer is the leading cause of cancer-related deaths worldwide. Approximately 85% of all lung cancers are non–small cell histology [non–small cell lung cancer (NSCLC)]. Modern treatment strategies for NSCLC target driver oncogenes and immune checkpoints. However, less than 15% of patients survive beyond 5 years. Here, we investigated the effects of SAR302503 (SAR), a selective JAK2 inhibitor, on NSCLC cell lines and tumors. We show that SAR is cytotoxic to NSCLC cells, which exhibit resistance to genotoxic therapies, such as ionizing radiation, cisplatin, and etoposide. We demonstrate that constitutive IFN-stimulated gene expression, including an IFN-related DNA damage resistance signature, predicts for sensitivity to SAR. Importantly, tumor cell–intrinsic expression of PD-L1 is IFN-inducible and abrogated by SAR. Taken together, these findings suggest potential dual roles for JAK2 inhibitors, both as a novel monotherapy in NSCLCs resistant to genotoxic therapies, and in tandem with immune checkpoint inhibition. Mol Cancer Ther; 17(4); 732–9. ©2018 AACR.