Citations 2
Landscape of Genomic Mechanisms of Resistance to Selective RET Inhibitors in RET -Altered Solid Tumors: Analysis of the RETgistry Global Consortium
Waliany, Sarah , Cooper, Alissa J. , Liu, Stephen V. , Gautschi, O., Rotow, Julia K. , Smith, Katherine E. , Weber, Urs, Lee, Dae Ho , Loong, H., Patel, Jyoti D. , Nagasaka, Misako , Patel, Shetal , Tan, Daniel S. W., Solomon, Benjamin J., Pall, Georg , Riess, Jonathan W. , Sun, Lova , Früh, Martin, Uy, Natalie F., Gadgeel, Shirish, Feng, Jamie, Leighl, Natasha B., Baik, Christina S. , Lai, G., Ou, S. Ignatius, Cheung, Kingsley S.Y., Patil, Tejas, Weiler, Daniela , Yeap, Beow Y., Wirth, Lori J. , Gainor, Justin F., Drilon, Alexander D., Lin, Jessica J., Loong, Herbert H. , Rotow, Julia , Gautschi, Oliver , Smith, Katherine E R , Weber, Urs M , Loong, Herbert H , Pennell, Nathan A , Nagasaka, Misako , Patel, Shetal A , Tan, Daniel S W , Solomon, Benjamin J , Kim, Tae Min , Pall, Georg , Riess, Jonathan W , Sun, Lova , Früh, Martin , Uy, Natalie F , Gadgeel, Shirish , Feng, Jamie , Do, Andrew , Falcon, Christina , Leighl, Natasha B , Baik, Christina S , Lai, Gillianne G Y , Ou, Sai-Hong I , Cheung, Kingsley S Y , Patil, Tejas , Mansfield, Aaron S , Weiler, Daniela , Yeap, Beow Y , Wirth, Lori J , Gainor, Justin F , Drilon, Alexander , Lin, Jessica J , Liu, Stephen V , Früh, Martin , Gadgeel, Shirish M. , Feng, Jamie , Mansfield, Aaron S. , Gainor, Justin F.
Clinical Cancer Research | January 15, 2026 | Volume: 32 | Issue: 6 | Pages: 1157-1168
Abstract Purpose: Rearranged during transfection (RET) alterations are oncogenic drivers across solid tumors. Selective RET inhibitors (SRI) selpercatinib and pralsetinib have transformed outcomes for patients with RET-altered malignancies. Limited knowledge exists on genomic mechanisms of resistance to SRI. Experimental Design: We established “RETgistry,” a global consortium of patients with advanced RET-altered solid tumors who received SRI and underwent postprogression tissue or plasma biopsies assessed by next-generation sequencing. Frequencies of secondary RET resistance mutations and acquired non-RET gene alterations were determined. Progression-free survival (PFS) and time to treatment discontinuation (TTD) on first SRI were estimated with the Kaplan–Meier method. Results: RETgistry included 109 patients with RET-altered advanced solid tumors (lung, n = 94; thyroid, n = 15) who underwent 143 post-SRI progression biopsies (tissue, 91; plasma, 52). The median PFS and TTD were 13.9 months [95% confidence interval (CI), 10.1–16.6] and 17.3 months (95% CI, 14–20.2), respectively. Secondary RET mutations were detected in 20 (14%) biopsies [lung cancer, 15 (12.4%) and thyroid carcinoma, 5 (22.7%)]. Common acquired off-target alterations involved MET (18.2%; amplification, 15%), TP53 (8.2%), APC (7.6%), KRAS (7.1%), KEAP1 (5.9%), and CDKN2A/B (5.3%). MET alterations were enriched in post-SRI versus pre-SRI specimens (full cohort, 17.6% vs. 2.0%, P = 0.022; lung cancer, 19.1% vs. 2.1%, P = 0.022). Conclusions: The prevalence of secondary RET mutations after SRI was low, underscoring a greater role for off-target resistance. Recurrent acquired alterations involving tumor suppressor genes or upstream regulators of MAPK and PI3K pathways were identified, most commonly MET amplification. Continued efforts to characterize SRI resistance biology are critical to guide the development of novel therapeutic strategies.
NCCN Guidelines® Insights: Small Cell Lung Cancer, Version 2.2026
Ganti, Apar Kishor P., Loo, B., Bassetti, Michael, Chiang, Anne, D’Avella, Christopher , Daly, Megan, Dowlati, Afshin, Edelman, Martin, Florsheim, Charles, Grecula, J.C., Hann, Christine, Khalil, Maya, Lee, R., Merritt, Robert E. , Mohindra, Nisha , Molina, Julian R. , Moran, C Solis, Mulvey, Claire K. , Osmundson, Evan C., Patel, S. B., Patil, Tejas, Puri, S., Qin, Angel, Tailor, Tina D. , Waqar, Saiama N., Cassara, Carly J., Ramakrishnan, Swathi , Ganti, Apar Kishor , Loo, Billy W. , Badiyan, Shahed N. , Bassetti, Michael, Bestvina, Christine M. , Chiang, Anne, Choudhury, Noura J. , Daly, Megan, Gold, Kathryn Ann , Goldman, Jonathan W. , Hann, Christine L. , Lee, Robert P. , Malhotra, Jyoti Dhar , Pokharel, Saraswati , Qin, Angel , Sands, Jacob , Shields, Misty Dawn , Waqar, Saiama N
Journal of the National Comprehensive Cancer Network | January 8, 2026 | Volume: 24 | Issue: 1 | Pages: No page available
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Small Cell Lung Cancer provide recommendations for diagnostic workup, staging, and treatment. These NCCN Guidelines Insights highlight recent updates, with a particular focus on changes to systemic therapies and radiation treatment in the NCCN Guidelines for Small Cell Lung Cancer.