Cancer of Unknown Primary: Challenges and Progress in Clinical Management

doi:10.3390/cancers13030451

Review

. 2021 Jan 25;13(3):451.

doi: 10.3390/cancers13030451.

Cancer of Unknown Primary: Challenges and Progress in Clinical Management

Noemi Laprovitera^{1

2}, Mattia Riefolo¹, Elisa Ambrosini¹, Christiane Klec³, Martin Pichler³, Manuela Ferracin¹

Affiliations

¹ Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy.
² Department of Life Sciences and Biotechnologies, University of Ferrara, 44121 Ferrara, Italy.
³ Division of Oncology, Medical University of Graz, 8036 Graz, Austria.

PMID: 33504059
PMCID: PMC7866161
DOI: 10.3390/cancers13030451

Review

Cancer of Unknown Primary: Challenges and Progress in Clinical Management

Noemi Laprovitera et al. Cancers (Basel). 2021.

. 2021 Jan 25;13(3):451.

doi: 10.3390/cancers13030451.

Authors

Noemi Laprovitera^{1

2}, Mattia Riefolo¹, Elisa Ambrosini¹, Christiane Klec³, Martin Pichler³, Manuela Ferracin¹

Affiliations

¹ Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy.
² Department of Life Sciences and Biotechnologies, University of Ferrara, 44121 Ferrara, Italy.
³ Division of Oncology, Medical University of Graz, 8036 Graz, Austria.

PMID: 33504059
PMCID: PMC7866161
DOI: 10.3390/cancers13030451

Abstract

Distant metastases are the main cause of cancer-related deaths in patients with advanced tumors. A standard diagnostic workup usually contains the identification of the tissue-of-origin of metastatic tumors, although under certain circumstances, it remains elusive. This disease setting is defined as cancer of unknown primary (CUP). Accounting for approximately 3-5% of all cancer diagnoses, CUPs are characterized by an aggressive clinical behavior and represent a real therapeutic challenge. The lack of determination of a tissue of origin precludes CUP patients from specific evidence-based therapeutic options or access to clinical trial, which significantly impacts their life expectancy. In the era of precision medicine, it is essential to characterize CUP molecular features, including the expression profile of non-coding RNAs, to improve our understanding of CUP biology and identify novel therapeutic strategies. This review article sheds light on this enigmatic disease by summarizing the current knowledge on CUPs focusing on recent discoveries and emerging diagnostic strategies.

Keywords: cancers of unknown primary site; clinical management; liquid biopsy; molecular profiling; primary site identification.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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[1] Chaffer C.L., Weinberg R.A. A perspective on cancer cell metastasis. Science. 2011;331:1559–1564. doi: 10.1126/science.1203543. - DOI - PubMed

[2] Chaffer C.L., Weinberg R.A. A perspective on cancer cell metastasis. Science. 2011;331:1559–1564. doi: 10.1126/science.1203543. - DOI - PubMed

[3] Fizazi K., Greco F.A., Pavlidis N., Daugaard G., Oien K., Pentheroudakis G., Committee E.G. Cancers of unknown primary site: Esmo clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2015;26(Suppl. S5):v133–v138. doi: 10.1093/annonc/mdv305. - DOI - PubMed

[4] Fizazi K., Greco F.A., Pavlidis N., Daugaard G., Oien K., Pentheroudakis G., Committee E.G. Cancers of unknown primary site: Esmo clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2015;26(Suppl. S5):v133–v138. doi: 10.1093/annonc/mdv305. - DOI - PubMed

[5] Golfinopoulos V., Pentheroudakis G., Kamakari S., Metaxa-Mariatou V., Pavlidis N. Donor-derived breast cancer in a bone marrow transplantation recipient. Breast Cancer Res. Treat. 2009;113:211–213. doi: 10.1007/s10549-008-9922-7. - DOI - PubMed

[6] Golfinopoulos V., Pentheroudakis G., Kamakari S., Metaxa-Mariatou V., Pavlidis N. Donor-derived breast cancer in a bone marrow transplantation recipient. Breast Cancer Res. Treat. 2009;113:211–213. doi: 10.1007/s10549-008-9922-7. - DOI - PubMed

[7] NCCN Occult Primary (Version 2.2020) [(accessed on 31 January 2020)]; Available online: https://www.nccn.org/professionals/physician_gls/pdf/occult_blocks.pdf.

[8] NCCN Occult Primary (Version 2.2020) [(accessed on 31 January 2020)]; Available online: https://www.nccn.org/professionals/physician_gls/pdf/occult_blocks.pdf.

[9] Massard C., Loriot Y., Fizazi K. Carcinomas of an unknown primary origin--diagnosis and treatment. Nat. Rev. Clin. Oncol. 2011;8:701–710. doi: 10.1038/nrclinonc.2011.158. - DOI - PubMed

[10] Massard C., Loriot Y., Fizazi K. Carcinomas of an unknown primary origin--diagnosis and treatment. Nat. Rev. Clin. Oncol. 2011;8:701–710. doi: 10.1038/nrclinonc.2011.158. - DOI - PubMed

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Cancer of Unknown Primary: Challenges and Progress in Clinical Management

Affiliations

Cancer of Unknown Primary: Challenges and Progress in Clinical Management

Authors

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Conflict of interest statement

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