Authors
Wafik S El-Deiry, Alberto Hernando-Calvo, Shai Magidi, Catherine Bresson, Sadakatsu Ikeda, Hikmat Abdel-Razeq, Arjun Oberoi, Susana Aguilar Izquierdo, Zhihuang Hu, Tobias Meissner, Rachel Elsey, Amal Al-Omari, Fanny Wunder, Razelle Kurzrock
Published in
Oncotarget. Volume 17. Issue 1. Pages 477-488. Oct 16, 2026.
Abstract
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. 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.
PMID:
42885719
Bibliographic data and abstract were imported from PubMed on 16 Oct 2026.
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