image: Figure 2: Treatment history timeline. The figure outlines the patient’s multimodal treatment timeline, including therapies, disease progression, and the timing of NGS and IHC sample analyses.
Credit: Copyright: © 2025 Hernando-Calvo 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.
“This case emphasizes the critical role of comprehensive molecular profiling and personalized therapeutic approaches in managing complex mCRC.”
BUFFALO, NY – June 24, 2025 – A new precision oncology paper was published in Volume 16 of Oncotarget on June 17, 2025, titled “Case Report WIN-MTB-2023001 WIN International Molecular Tumor Board A 62-year-old male with metastatic colorectal cancer with 5 prior lines of treatment.”
In this report, led by Alberto Hernando-Calvo from Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology; Razelle Kurzrock from WIN Consortium and Medical College of Wisconsin; Oncotarget Editor-in-Chief Wafik S. El-Deiry from WIN Consortium and Legorreta Cancer Center at Brown University; and corresponding author Shai Magidi, also from WIN Consortium, along with colleagues, describe the case of a 62-year-old man with metastatic colorectal cancer who underwent multiple lines of therapy. After analysis, the WIN International Molecular Tumor Board proposed different personalized treatment plans based on the tumor’s unique genetic mutations. This case highlights the growing role of precision oncology in guiding therapies for patients with treatment-resistant cancers.
Colorectal cancer is one of the deadliest cancers worldwide, and managing advanced cases remains a significant challenge. This patient had already received five prior treatment regimens, including chemotherapy and targeted therapies. Although some treatments were initially beneficial, the cancer eventually developed resistance. Molecular analysis revealed key mutations in genes such as BRAF, MET, APC, TP53, and NRAS, which are often linked to aggressive tumor behavior and reduced treatment effectiveness.
With limited standard options left, the patient’s case was presented and reviewed by the WIN International Molecular Tumor Board, a global panel of cancer experts. The team analyzed the clinical history and genetic profile to design new treatment approaches. These involved off-label drug combinations tailored to the specific mutations found in the tumor. For example, one approach combined trametinib, a drug that blocks cancer cell growth signals, with amivantamab, an antibody that attacks cancer-related proteins MET and EGFR, and regorafenib, which helps cut off blood supply to tumors and may counteract effects from APC and TP53 mutations.
“Another option was trametinib at 1 mg daily, cetuximab (EGFR antibody), 250 mg/m² IV every two-weeks, and cabozantinib (MET and VEGFR inhibitor), 40 mg po daily.”
This case reflects a shift in cancer care from standardized protocols to precision approaches, where therapy is selected based on a tumor’s molecular features. Such strategies aim to delay resistance and slow disease progression more effectively. The WIN International Molecular Tumor Board also discussed practical challenges, including access to medications, combining off-label drugs, and the difficulties of enrolling patients in clinical trials after multiple prior treatments.
Although the ultimate treatment decision remained with the patient’s physician, this report shows how international collaboration and precision oncology can expand options for patients facing limited alternatives. It also emphasizes the value of repeat genetic analysis during disease progression to monitor new mutations in the tumor that may impact treatment.
While the patient ultimately died from cancer progression, this case serves as a model for how molecular analysis and expert input can be used to guide treatment even in complex and metastatic colorectal cancer. As personalized cancer strategies continue to evolve, they may offer potential pathways for patients who have exhausted standard treatment options.
Continue reading: DOI: https://doi.org/10.18632/oncotarget.28744
Correspondence to: Shai Magidi – shai.magidi@winconsortium.org
Keywords: cancer, precision oncology, molecular tumor board, colorectal carcinoma, cancer management
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Journal
Oncotarget
Method of Research
Case study
Subject of Research
People
Article Title
Case Report WIN-MTB-2023001 WIN International Molecular Tumor Board A 62-year-old male with metastatic colorectal cancer with 5 prior lines of treatment
Article Publication Date
17-Jun-2025
COI Statement
• R.K. has received research funding from Boehringer Ingelheim, Debiopharm, Foundation Medicine, Genentech, Grifols, Guardant, Incyte, Konica Minolta, Medimmune, Merck Serono, Omniseq, Pfizer, Sequenom, Sysmex, Takeda, and TopAlliance and from the NCI; as well as consultant and/or speaker fees and/or advisory board/consultant for Actuate Therapeutics, AstraZeneca, Bicara Therapeutics, Inc., Biological Dynamics, Caris, Daiichi, Datar Cancer Genetics, EISAI, EMD Serono, EOM Pharmaceuticals, Iylon, Jackson Laboratories, LabCorp, Lanauria Therapeutics, Merck, NeoGenomics, Neomed, Pfizer, Precirix, Prosperdtx, Quanta Therapeutics, Recordati, Regeneron, Roche, TD2/Volastra, Turning Point Therapeutics, X-Biotech; has an equity interest in CureMatch Inc.; serves on the Board of CureMatch and CureMetrix and XZOM, and is a co-founder of CureMatch. • A.H.C. reports grant support from Gilead (institution); payment or honoraria from Grupo Español de Tumores de cabeza y Cuello (TTCC); travel support for meeting attendance from Kyowa Kirin, MSD, and Bristol Myers Squibb; and payment for expert testimony from Slingshot insights. • W.S.E-D. is Chair of the Worldwide Innovative Network (WIN) Association – WIN Consortium and Scientific Founder of Oncoceutics, Inc. (acquired by Chimerix, Inc.), SMURF-Therapeutics, and p53-Therapeutics. He is receiving or has received recent funding from NIH/NCI, American Cancer Society, The Warren Alpert Foundation, AACR-Novocure, D&D Phramatech, Chimerix, AstraZeneca, and Actuate Therapeutics. W.S.E-D. serves on the Executive Committee of the Caris Life Sciences Precision Oncology Alliance, and as co-Editor-in-Chief of Oncotarget, the journal that invited this manuscript in a “Collection of articles on Precision Oncology.” W.S.E-D. was not involved in the review of this manuscript or the decision to accept it. • S.M. receives consultancy fees from the Worldwide Innovative Network (WIN) Association - WIN Consortium. • C.B. and F.W. are full-time employees of the Worldwide Innovative Network (WIN) Association - WIN Consortium.