Precision oncology has advanced rapidly over the past decade, driven by increased access to next-generation sequencing and the growing number of approved biomarker-specific therapies. However, identifying the most appropriate treatment options for some patients remains challenging, particularly for those with rare tumor types, childhood cancers, or resistance to first-line therapies.
Although randomized controlled clinical trials are foundational for evidence-based medicine, clinical case reports offer complimentary evidence by detailing patient responses to therapy within specific molecular context, including off-label drug use. However, mining clinical case report data from resources such as PubMed is often time-consuming and inefficient, particularly in clinical settings, which has limited their widespread use.
Genomenon’s Cancer Knowledgebase (CKB) addresses this challenge by transforming published clinical case reports into searchable evidence, complete with genomic profiles, tumor types, therapies, and treatment response. CKB is an expertly-curated relational database designed to support the interpretation of somatic variants and identification of relevant therapeutic options, integrating data from scientific literature, covering cancer genomic profiles, therapies, clinical and preclinical evidence, and clinical trials. A key differentiator of CKB is its meticulous curation of evidence from clinical case reports.
In the recent publication from Gokhale et al.1, curated content within CKB was successfully leveraged for querying and analyzing case report data to determine utility and actionability. At the time of that analysis, CKB contained more than 5,500 unique evidence annotations related to case reports, spanning 2,800 molecular profiles across 500 genes and 300 different tumor types. This case report evidence captures patient responses to both FDA-approved and investigational therapies.
Key Findings: The Value of Curated Case Reports
Therapeutic Response Types:
The evidence curation process in CKB uses a controlled vocabulary for response, which includes 'sensitive' and 'resistant.' Among the case report evidence annotations , 63% referenced sensitivity to therapy while 25% included resistance, providing a critical, balanced view of therapy outcomes.
Molecular Context and Tumor Diversity:
Each clinical case report evidence annotation is linked to a molecular profile, often comprising one or more genomic alterations (with a large number including an EGFR mutation). These case reports span 380 tumor types, with the majority related to respiratory system, gastrointestinal system, and hematologic cancers.
Uncovering Actionable Insights in Complex Cases:
The true value of curated case reports becomes apparent in patient segments where evidence is limited.
Rare Tumor Types:
CKB contains crucial evidence for rare tumor types such as intrahepatic cholangiocarcinoma (ICC). While only a handful of approved therapies exist, CKB captures case report evidence describing responses across 12 therapies and a diversity of 30 unique FGFR2 fusions, a common alteration in ICC. Similarly, for congenital fibrosarcoma, a rare pediatric tumor typically associated with ETV6-NTRK3 fusions, CKB features case reports involving alternative NTRK fusion partners. These reports provide response data for 7 different therapies, expanding potential treatment considerations for patients with rare alterations.
Childhood Cancers:
Precision medicine offers new strategies for the treatment of childhood cancers. With hematologic and central nervous system tumors being the most common, 63% of the pediatric case report evidence in CKB relates to these types. The majority are linked to fusions (52%), which are common in several childhood cancers. While standard-of-care options exist, the analysis of pediatric case reports in CKB reveals numerous targeted therapy options for indications including sarcoma, neuroblastoma, and glioblastoma.
Overcoming Therapeutic Resistance:
CKB provides significant utility when needing to identify alternative treatment options for patients who develop therapeutic resistance. For example, patients with melanoma treated with a BRAF inhibitor often develop resistance due to acquisition of a secondary resistance mutation. CKB contains more than 30 case report evidence annotations related to BRAF inhibitor resistance in patients with BRAF V600E-mutated melanoma across 13 different therapies, offering deeper insights into resistance mechanisms.
Guiding Difficult Treatment Decisions:
For specific biomarkers with multiple treatment options, or those resistant to standard treatment, case report evidence is invaluable. This is especially true for EGFR exon 20 insertions, which are often resistant to tyrosine kinase inhibitors. CKB includes 64 evidence annotations across 23 specific EGFR exon 20 insertion mutations treated with approved EGFR targeted therapies. Importantly, it also captures 110 evidence annotations across 15 investigational therapies and 45 unique EGFR exon 20 insertion mutations, providing a comprehensive view of patient responses to guide treatment choice.
Supporting Off-Label Use:
Clinical case reports are often the only source of data to support the off-label use of approved therapies when a patient has exhausted all standard of care options. Notably, CKB curated case report annotations documented the use of immune checkpoint inhibitors in colorectal cancer patients with POLE mutations and high tumor mutational burden as early as 2023, well before this treatment approach was included in professional guidelines in 2025.
Wrap-up: Elevating Case Reports as Actionable Evidence
Clinical case report data has historically been viewed as less impactful, largely because their findings are difficult to aggregate and analyze. CKB overcomes these limitations through its robust structure, organization, and expert curation processes, transforming case reports into data that can be easily queried across critical dimensions, including molecular profiles, therapies, tumor type, and response types. While other knowledgebases exist, many lack consistent maintenance or exclude clinical case report evidence altogether. CKB is regularly updated and uniquely positioned to uncover additional actionable insights from clinical case report data, offering a more complete and clinically meaningful view of patient treatment journeys in precision oncology.
References:
- Gokhale, R, et al. Leveraging oncology clinical case report data through the Cancer Knowledgebase (CKB). Per Med. 2025 Nov 3:1-13
