Abstract
Cancer of unknown primary (CUP) accounts for approximately 3% of all malignancies. Despite extensive laboratory and imaging efforts, the primary site usually cannot be unequivocally confirmed, and the treatment for the most part remains empirical. Recently, identification of common cancer pathway alterations in diverse cancer lineages has offered an opportunity to provide targeted therapies for patients with CUP, irrespective of the primary site. 1806 cancers of unknown primary were identified among more than 63,000 cases profiled at Caris Life Sciences. Multiplatform profiling of the tumor samples included immunohistochemistry, gene sequencing and in situ hybridization methods in an effort to identify changes in biomarkers that are predictive of drug responses. Biomarkers associated with a potential drug benefit were identified in 96% of cases. Biomarkers identified included those associated with potential benefit in nearly all classes of approved cancer drugs (cytotoxic, hormonal, targeted biological drugs). Additionally, biomarkers associated with a potential lack of benefit were identified in numerous cases, which could further refine the management of patients with CUP. Comprehensive biomarker profiling of CUP may provide additional choices in treatment of patients with these difficult to treat malignancies.
Highlights
Cancer of unknown primary (CUP) is a heterogeneous clinicopathologic syndrome constituting 3% of all malignancies [1]
Biomarkers associated with a potential lack of benefit were identified in numerous cases, which could further refine the management of patients with CUP
The diagnosis of CUP was previously established in all cases from the referring clinicians and institutions; IHC stains performed at the referring pathology laboratories did not unequivocally establish the primary site in any of the cases tested
Summary
Cancer of unknown primary (CUP) is a heterogeneous clinicopathologic syndrome constituting 3% of all malignancies [1]. In true CUP by definition, the diagnosis of the primary cancer cannot be verified. In all such cases administration of presumed primary site-specific therapy remains empirical and for most cases is not driven by predictive biomarkers [5]. Identification of shared, actionable pathway alterations in tumors from diverse primary sites has offered an opportunity to suggest pathway-specific therapies independent of tissue lineage [9,10,11,12]. Identification of common cancer pathway alterations in diverse cancer lineages has offered an opportunity to provide targeted therapies for patients with CUP, irrespective of the primary site
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