“ This case underscores the complexity of managing MPC and highlights the essential role of international molecular tumor boards in generating innovative, tailored treatment recommendations for patients with rare and multifaceted disease courses. ”
BUFFALO, NY – July 22, 2026 – A new precision oncology paper was published in Volume 17 of Oncotarget on July 21, 2026, titled “ WIN-MTB-2024017 – WIN International Molecular Tumor Board: A 48-year-old female with multiple primary cancers .”
The study was led by Oncotarget Editor-in-Chief, Dr. Wafik S. El-Deiry, from the Worldwide Innovative Network (WIN) Association – WIN Consortium and Legorreta Cancer Center at Brown University .
Patients who develop multiple primary cancers face unique diagnostic and treatment challenges because each tumor may have distinct biological characteristics requiring different therapeutic approaches. Advances in genomic profiling and precision oncology now enable clinicians to better distinguish between independent tumors and recurrent disease while identifying molecular alterations that may guide individualized treatment strategies. This case report demonstrates how an international molecular tumor board integrated comprehensive genomic data with multidisciplinary expertise to develop personalized recommendations for a patient with an exceptionally complex cancer history.
The case describes the clinical journey of a 48-year-old woman carrying a germline BRCA1 mutation who developed multiple primary cancers over nearly two decades, including breast cancer, basal cell carcinoma of the skin, high-grade serous ovarian carcinoma, colon cancer, and small bowel adenocarcinoma. During this time, she underwent multiple surgeries, chemotherapy regimens, targeted therapy with the PARP inhibitor niraparib, and extensive molecular testing to characterize each malignancy.
Comprehensive genomic profiling revealed that although the patient’s cancers shared the inherited BRCA1 mutation, each tumor acquired additional somatic alterations that distinguished one malignancy from another. The colon and small bowel tumors both carried an identical PIK3CA C420R mutation, supporting the conclusion that the small bowel tumor most likely represented recurrence of the previous colon cancer rather than an independent primary malignancy. In contrast, the ovarian tumor demonstrated a different molecular profile, including a TP53 mutation and features consistent with high-grade serous ovarian carcinoma.
The investigators also identified a previously unreported BRCA1-STARD3 gene fusion in metastatic ovarian cancer tissue. While the functional significance of this fusion has not yet been experimentally validated, the authors note that it represents a novel finding that may warrant further investigation. The case illustrates how comprehensive molecular profiling can uncover uncommon genomic alterations that may provide new insights into cancer biology and future therapeutic opportunities.
An international Molecular Tumor Board (MTB), organized through the Worldwide Innovative Network (WIN) Consortium, reviewed the patient’s clinical history and molecular findings. Rather than recommending a single treatment, the panel discussed several personalized management strategies that could be considered if the disease recurs. These included combinations of targeted therapies directed at EGFR, PIK3CA, and BRCA1-associated pathways, immunotherapy combinations, anti-angiogenic therapy, aspirin for PIK3CA-mutated colorectal cancer, circulating tumor DNA monitoring, and investigational therapeutic vaccines targeting PIK3CA, STARD3, and mutant TP53. The recommendations were intended to guide future clinical decision-making based on the patient’s molecular profile rather than represent established standards of care.
The experts also emphasized the importance of continued surveillance using regular imaging and circulating tumor DNA testing to monitor for recurrence. They noted that repeated molecular profiling may help refine treatment decisions as tumors evolve and as new targeted therapies become available. The case highlights how precision oncology can support ongoing clinical decision-making throughout a patient’s cancer journey.
“ This case exemplifies the critical importance of clinical persistence and the transformative potential of precision medicine in complex oncology cases .”
According to the authors, molecular profiling should be viewed as an evolving clinical tool capable of revealing new therapeutic opportunities throughout the course of treatment. They emphasize that patient management should remain dynamic, with treatment recommendations periodically reassessed as molecular technologies advance and knowledge of targetable cancer pathways continues to expand.
Overall, this case demonstrates how international molecular tumor boards can support personalized cancer care by combining detailed clinical evaluation with comprehensive genomic profiling. Although many of the proposed therapeutic strategies remain investigational or off-label, the report highlights the growing role of precision oncology in helping clinicians develop individualized treatment plans for patients with rare and highly complex cancer histories.
DOI: https://doi.org/10.18632/oncotarget.28899
Correspondence to: Wafik S. El-Deiry – wafik_el-deiry@brown.edu
Keywords : cancer, precision oncology, molecular tumor board
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WIN-MTB-2024017 – WIN International Molecular Tumor Board: A 48-year-old female with multiple primary cancers
21-Jul-2026
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. C.B. and F.W. are full time employees of Worldwide Innovative Network (WIN) Association – WIN Consortium. S.M. receives consultancy from Worldwide Innovative Network (WIN) Association – WIN Consortium. R.K. is Chief Medical Officer of the Worldwide Innovative Network (WIN) Association – WIN Consortium and 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. J.L. receives honoraria from Specialised Therapeutics, Taiho, and MSD. Her institution receives consulting funding for Starpharma, Greywolf Therapeutics, and Merck. J.L. receives travel expenses support from Innovent Biologics, Starpharma and ImmVirX. Her institution receives research funding from AbbVie, AVEO, Bayer, BMS, Carina Biotech, Corvus Pharmaceuticals, Daiichi Sankyo, Greywolf Therapeutics, ImmVirX, Innovent Biologics, Merus, Merck, MSD, Relay Therapeutics, Regeneron, Starpharma, and Virocure. A.H.C. declares consultant or advisory roles in the following companies, Boehringer Ingelheim, Slingshot Insights, and Karger Publishers (personal), research funding from GSK, Bayer, Boehringer Ingelheim, CDR-life, Novartis, Vividion therapeutics and NEC Bio (all institution), grant support from Gilead (institution) and financial interest from CDDF and Fundación SEOM.