Citations 2
Outcomes for Sinonasal Undifferentiated Carcinoma (SNUC): An International Multi-Center Retrospective Cohort Study
Liu, Jacklyn , Takahashi, Yoko , Rehman, Umar , Turri-Zanoni, Mario, Mattavelli, Davide, Counsell, Nicholas , Ferrari, Marco, Rampinelli, Vittorio , Vermi, William , Lombardi, Davide , Saade, Rami , Park, Ki Wan , Emanuel, Oscar , Schartinger, Volker Hans , Franchi, Alessandro , Facco, Carla, Sessa, Fausto, Battocchio, Simonetta , Eriksen, Patrick René Gerhard , Haddouchi, Mohamed El, Maragliano, Roberta , Lelkaitis, Giedrius , Saraswathula, Anirudh, KAUR, RAMAN PREET, Mydlarz, Wojciech K. , Ishii, Masaru, Dave, Manas, Fenton, Tim R. , Lim, Alison E. , Okhovat, Saleh , Elegio, Gyleen, Pouvreau, Pierre, Thariat, Juliette, Digue, L., Ferrand, François-Régis, Costes-Martineau, Valerie, Castain, Claire, Kermadec, H. De , O’Neill, James Paul, Lacy, Peter D., Vaz, Francis, O’Flynn, Paul, Howard, David J., Stimpson, Paul, Wang, S, Royle, Gary , Steele, Christopher, Jay, A., Carnell, Dawn , Forster, Martin D., Thomson, David, Buchwald, Christian von, Lllorente, Jose Luis, Hermsen, Mario A., Jurmeister, Philipp , Capper, David, Gallia, Gary L. , Js, Tay, Mohyeldin, Ahmed, Fernandez-Miranda, Juan, LE, Q, West, Robert B., Patel, Z M, Hwang, P H, Facchetti, Fabio , Nicolai, Piero, Ferrarotto, Renata, Phan, Jack, Bossi, P., Castelnuovo, P., Moya-Plana, Antoine, Verillaud, B., Garnis, Cathie , Thamboo, Andrew , Olawuni, Felicia O., Moore, E.J., Choby, Garret M., Lal, Devyani, Akhave, Neal S. , Bell, Diana , Su, Shirley Y., Lund, Valerie J., London, Nyall R. , HANNA, Ehab, Lechner, Matt, Hwang, Peter H. , Thariat, Juliette , Phan, Jack , Le, Quynh‐Thu , Patel, Zara M. , Franchi, Alessandro , Su, Shirley Y. , Lund, Valerie J. , Lechner, Matt , Castelnuovo, Paolo , Ferrari, Marco , Turri‐Zanoni, Mario , Mattavelli, Davide , Moya‐Plana, Antoine , Rehman, Umar , Turri-Zanoni, Mario , Mattavelli, Davide , Ferrari, Marco , Schartinger, Volker H , Maragliano, Roberta , Lelkaitis, Giedrius , Fenton, Tim R , Thariat, Juliette , Ferrand, Francois-Regis , Howard, David J , Carnell, Dawn , Forster, Martin D , von Buchwald, Christian , Hermsen, Mario , Tay, Joshua K , Le, Quynh-Thu , Patel, Zara , Hwang, Peter H , Facchetti, Fabio , Phan, Jack , Bossi, Paolo , Castelnuovo, Paolo , Moya-Plana, Antoine , Olawuni, Felicia, Su, Shirley Y , Lund, Valerie J , Lechner, Matt , Sessa, Fausto , Bendtsen, Simone K. , Jakobsen, Kathrine Kronberg , Saraswathula, Anirudh , Ramanathan, Murugappan , Ishii, Masaru, Dupin, Charles Louis , Digue, Laurence, Costes‐Martineau, Valérie , Castain, Claire , Hintze, Justin , O'Flynn, Paul E., Steele, Christopher D. , Woods, Robbie , Llorente Pendás, José Luis , Capper, David , Nayak, Jayakar V. , Nicolai, Piero , Vérillaud, Benjamin , Choby, Garret , Hanna, Ehab Y.
Cancers | January 26, 2026 | Volume: 18 | Issue: 3 | Pages: 366
Background: Sinonasal undifferentiated carcinoma (SNUC) is an extremely rare, high-grade, and aggressive tumor of the sinonasal tract. Due to the rarity of this malignancy, current treatment guidelines are based on small and often/mainly single-center retrospective datasets. In the absence of a universally accepted standard of care for SNUC, treatment approaches vary across countries and institutions, reflecting real-world clinical practice. The primary aim of this study was to describe real-world treatment and outcomes for patients with confirmed SNUC. Methods: This was an international, multi-center, retrospective, observational cohort study that pooled patients into the largest SNUC dataset to date. Fifteen centers were enrolled to contribute data, including seven from Europe, four from the United States, three from the United Kingdom, and one from Canada. In the absence of a universally accepted standard of care for SNUC, treatment approaches varied across countries and institutions, reflecting real-world clinical practice. Patients included were those with histologically confirmed SNUC who were treated between 1997 and 2021. Results: This study yielded 485 patients treated for SNUC. The median age at diagnosis was 55.6 years (IQR: 44.5–67.6), and 63.7% were male. Most cases presented at advanced stages, with 70.8% as T4a or T4b. Overall survival (OS) outcomes were available for 412 patients, with a median follow-up of 26.0 months. The 5- and 10-year OS were 47.2% (95% CI: 40.8–53.3%) and 39.6% (95% CI: 32.5–46.6%), respectively. Advanced age, dichotomized T-stage (T4a/b vs. T1–3), M-stage, and orbital involvement were significant poor prognostic factors on univariable analysis (p’s < 0.01). On multivariable analysis, orbital involvement (HR: 2.73, 95% CI: 1.42–5.27, p = 0.003) and distance metastasis stage (HR: 3.00, 95% CI: 1.25–7.21, p = 0.014) were both independently associated with worse OS. Conclusions: This observational study presents the largest multi-center cohort analysis of SNUC to date, providing new insights into prognostic factors for a rare cancer treated at global centers of excellence. Orbital involvement and the presence of metastases are candidate independent risk factors associated with poorer OS.
Aberrant Expression and Subcellular Localization of ECT2 Drives Colorectal Cancer Progression and Growth
Cook, Danielle , Martin, Timothy D. , Galanko, Joseph A. , Loeza, Gabriela Herrera, Trembath, Dimitri G. , Justilien, Verline , Pickering, Karen , Jarosch, Armin , Jurmeister, Philipp , Waters, Andrew M. , Hibshman, Priya S. , Campbell, Andrew D. , Yeh, Jen Jen , Lee, Michael S. , Fields, Alan P. , Sandler, Robert S. , Sansom, Owen J. , Sers, Christine , Schaefer, Antje , Martin, Timothy D , Trembath, Dimitri G , Justilien, Verline , Pickering, Karen A , Waters, Andrew M , Lee, Michael S , Cox, Adrienne D , Sandler, Robert S , Sansom, Owen J , Sers, Christine , Schaefer, Antje , Kang, Melissa S , Loeza, Gabriela H., Vincent, David F. , Ford, Catriona A. , Keku, Temitope O , Cox, Adrienne D. , Der, Channing J
Cancer Research | November 4, 2021 | Volume: 82 | Issue: 1 | Pages: 90-104
Abstract ECT2 is an activator of RHO GTPases that is essential for cytokinesis. In addition, ECT2 was identified as an oncoprotein when expressed ectopically in NIH/3T3 fibroblasts. However, oncogenic activation of ECT2 resulted from N-terminal truncation, and such truncated ECT2 proteins have not been found in patients with cancer. In this study, we observed elevated expression of full-length ECT2 protein in preneoplastic colon adenomas, driven by increased ECT2 mRNA abundance and associated with APC tumor-suppressor loss. Elevated ECT2 levels were detected in the cytoplasm and nucleus of colorectal cancer tissue, suggesting cytoplasmic mislocalization as one mechanism of early oncogenic ECT2 activation. Importantly, elevated nuclear ECT2 correlated with poorly differentiated tumors, and a low cytoplasmic:nuclear ratio of ECT2 protein correlated with poor patient survival, suggesting that nuclear and cytoplasmic ECT2 play distinct roles in colorectal cancer. Depletion of ECT2 reduced anchorage-independent cancer cell growth and invasion independent of its function in cytokinesis, and loss of Ect2 extended survival in a KrasG12D Apc-null colon cancer mouse model. Expression of ECT2 variants with impaired nuclear localization or guanine nucleotide exchange catalytic activity failed to restore cancer cell growth or invasion, indicating that active, nuclear ECT2 is required to support tumor progression. Nuclear ECT2 promoted ribosomal DNA transcription and ribosome biogenesis in colorectal cancer. These results support a driver role for both cytoplasmic and nuclear ECT2 overexpression in colorectal cancer and emphasize the critical role of precise subcellular localization in dictating ECT2 function in neoplastic cells. Significance: ECT2 overexpression and mislocalization support its role as a driver in colon cancer that is independent from its function in normal cell cytokinesis.