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Life sciences · Journal article
Oncotarget · October 16, 2026
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Wafik S. El-Deiry1,2,*, Alberto Hernando-Calvo3, Shai Magidi1, Catherine Bresson1, Sadakatsu Ikeda5, Hikmat Abdel-Razeq6, Arjun Oberoi3, Susana Aguilar Izquierdo3, Zhihuang Hu4, Tobias Meissner7, Rachel Elsey7, Amal Al-Omari6, Fanny Wunder1 and Razelle Kurzrock1,8,* 1 Worldwide Innovative Network (WIN) Association - WIN Consortium, Chevilly-Larue 94550, France 2 Legorreta Cancer Center at Brown University, Providence, Rhode Island 02912, USA 3 Vall d'Hebron Hospital Campus and Institute of Oncology (VHIO), Barcelona 08035, Spain 4 Fudan University Shanghai Cancer Center, Shanghai 200032, China 5 Institute of Science Tokyo Hospital Tokyo 113-8510, Japan 6 King Hussein Cancer Center, Amman 11941, Jordan 7 Avera Cancer Institute, Sioux Falls, South Dakota 57105, USA 8 Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA * These authors contributed equally to this work Correspondence to: Wafik S. El-Deiry, email:wafik@brown.edu Keywords: cancer; precision oncology; molecular tumor board; colon cancer Received: April 15, 2026 Accepted: September 15, 2025 Published: October 16, 2026 Copyright: © 2026 El-Deiry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with a complex molecular profile that impacts tumor behavior and treatment response. This case report discusses a 52-year-old female diagnosed with Stage IIIc colon cancer, exhibiting KRAS, TP53, IDH1, and APC mutations, as well as a tumor microenvironment with high PD-L1 expression and elevated VEGFR1 and VEGFR3. Despite surgical resection and adjuvant treatment which included FOLFOX, FOLFIRI with bevacizumab and local radiation, the patient’s disease was difficult to track due to small, non-FDG-avid lymph nodes in the aortocaval region and persistent circulating tumor DNA (ctDNA). Following a review by an international Molecular Tumor Board (MTB), maintenance therapy options were discussed, including the personalized combinations of regorafenib, sulindac, and metformin, or fruquintinib, sulindac, and metformin, based on the patient’s molecular alterations. Alternatively, 5-FU with or without bevacizumab was suggested. In the event of relapse, the MTB recommended the combination of regorafenib, sulindac, and metformin, with the addition of trametinib and ivosidenib. The combination of regorafenib, ipilimumab, and nivolumab (RIN) was also considered due to the patient’s high PD-L1 expression. Further clinical trial options, such as pan-RAF inhibitors, NK cell agonists, and TAS-102 with bevacizumab, were also discussed. Additionally, the potential combination of PD-1 and TGFβ inhibitors was explored. This case underscores the critical role of molecular profiling in tailoring personalized treatment strategies for advanced CRC, providing novel avenues for managing recurrent disease, even in the absence of measurable disease.