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| 001 | 303375 | ||
| 005 | 20250810021956.0 | ||
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| 100 | 1 | _ | |a Pouyiourou, Maria |0 P:(DE-He78)d62d536fb73eb7644201ddaac56cf68f |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a Rethinking cancer of unknown primary: from diagnostic challenge to targeted treatment. |
| 260 | _ | _ | |a New York, NY |c 2025 |b Nature Publ. Group |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 520 | _ | _ | |a Cancer of unknown primary (CUP) is a metastatic malignancy for which a primary site of origin cannot be identified despite a thorough and standardized diagnostic work-up, and accounts for 1-3% of all malignancies. An unfavourable subgroup of CUP has a poor prognosis, with a median overall survival of <1 year when treated with current standard-of-care platinum-based chemotherapy. Virtually no progress in elucidating the disease biology and improving outcomes for patients with unfavourable CUP has been made over the past several decades, including a failure of initial randomized clinical trials to demonstrate the superiority of tissue-of-origin (ToO) identification by gene-expression profiling and subsequent primary-site-directed treatment over standard chemotherapy. However, large-cohort randomized trials have now shown that molecularly guided therapy improves outcomes for patients with CUP harbouring an actionable target, both in a tissue-agnostic as well as a primary tumour site-specific context. Moreover, data from non-randomized phase II trials suggest that immunotherapy using immune-checkpoint inhibitors can be beneficial even in patients with CUP that has relapsed after, or is refractory to, standard chemotherapy. In addition, a plethora of refined and novel strategies, including DNA and RNA sequencing, DNA-methylation profiling, circulating tumour DNA analysis, and artificial intelligence-based pathology, have been leveraged to facilitate ToO identification. In light of these developments, we review current ToO methodologies and compare the evidence supporting the use of a primary tumour site-guided approach versus a histology-agnostic approach to the management of CUP. We also discuss whether CUP can be viewed as a model disease for the development of histology-agnostic precision oncology treatment strategies. |
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| 700 | 1 | _ | |a Bochtler, Tilmann |0 P:(DE-He78)c741dc7f974390ad4310349f29aac40b |b 1 |u dkfz |
| 700 | 1 | _ | |a Pauli, Chantal |b 2 |
| 700 | 1 | _ | |a Moch, Holger |0 0000-0002-7986-2839 |b 3 |
| 700 | 1 | _ | |a Brobeil, Alexander |b 4 |
| 700 | 1 | _ | |a Pantel, Klaus |0 0000-0001-5736-2772 |b 5 |
| 700 | 1 | _ | |a Stenzinger, Albrecht |0 0000-0003-1001-103X |b 6 |
| 700 | 1 | _ | |a Krämer, Alwin |0 P:(DE-He78)493c5fbf69f1b20df6f048712f3ad4a0 |b 7 |e Last author |u dkfz |
| 773 | _ | _ | |a 10.1038/s41571-025-01060-8 |0 PERI:(DE-600)2491414-9 |p nn |t Nature reviews / Clinical oncology |v nn |y 2025 |x 1759-4774 |
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