Correction: Activation of the IFN Signaling Pathway is Associated with Resistance to CDK4/6 Inhibitors and Immune Checkpoint Activation in ER-Positive Breast Cancer
| العنوان: | Correction: Activation of the IFN Signaling Pathway is Associated with Resistance to CDK4/6 Inhibitors and Immune Checkpoint Activation in ER-Positive Breast Cancer |
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| المؤلفون: | Carmine De Angelis, Xiaoyong Fu, Maria Letizia Cataldo, Agostina Nardone, Resel Pereira, Jamunarani Veeraraghavan, Sarmistha Nanda, Lanfang Qin, Vidyalakshmi Sethunath, Tao Wang, Susan G. Hilsenbeck, Matteo Benelli, Ilenia Migliaccio, Cristina Guarducci, Luca Malorni, Lacey M. Litchfield, Jiangang Liu, Joshua Donaldson, Pier Selenica, David N. Brown, Britta Weigelt, Jorge S. Reis-Filho, Ben H. Park, Sara A. Hurvitz, Dennis J. Slamon, Mothaffar F. Rimawi, Valerie M. Jansen, Rinath Jeselsohn, C. Kent Osborne, Rachel Schiff |
| المصدر: | Clin Cancer Res |
| بيانات النشر: | American Association for Cancer Research (AACR), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cancer Research, Oncology, Article |
| الوصف: | PURPOSE: CDK4/6 inhibitors are highly effective against ER+/HER2- breast cancer (BC); however, intrinsic and acquired resistance is common. Elucidating the molecular features of sensitivity and resistance to CDK4/6i’s may lead to identification of predictive biomarkers and novel therapeutic targets, paving the way toward improving patient outcomes. EXPERIMENTAL DESIGN: Parental BC cells and their endocrine-resistant derivatives (EndoR) were used. Derivatives with acquired resistance to palbociclib (PalboR) were generated from parental and estrogen-deprivation resistant MCF7 and T47D cells. Transcriptomic and proteomic analyses were performed in palbociclib-sensitive and PalboR lines. Gene expression data from CDK4/6i neoadjuvant trials and publicly available datasets were interrogated for correlations of gene signatures and patient outcomes. RESULTS: Parental and EndoR BC lines showed varying degrees of sensitivity to palbociclib. Transcriptomic analysis of these cell lines identified an association between high interferon (IFN) signaling and reduced CDK4/6i sensitivity; thus an ‘IFN-Related Palbociclib-Resistance Signature’ (IRPS) was derived. In two neoadjuvant trials of CDK4/6i plus endocrine therapy, IRPS and other IFN-related signatures were highly enriched in patients with tumors exhibiting intrinsic resistance to CDK4/6i. PalboR derivatives displayed dramatic activation of IFN/STAT1-signaling compared to their short-term treated or untreated counterparts. In primary ER+/HER2- tumors, the IRPS score was significantly higher in lumB than lumA subtype and correlated with increased gene expression of immune checkpoints, endocrine resistance, and poor prognosis. CONCLUSION: Aberrant IFN-signaling is associated with intrinsic resistance to CDK4/6i. Experimentally, acquired resistance to palbociclib is associated with activation of the IFN-pathway, warranting additional studies to clarify its involvement in resistance to CDK4/6i. |
| تدمد: | 1557-3265 1078-0432 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5251d708cd344a4678ec8d623580af49Test https://doi.org/10.1158/1078-0432.ccr-21-2431Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5251d708cd344a4678ec8d623580af49 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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