Precision oncology promised to transform cancer care by matching patients to targeted therapies based on their tumor’s genetic makeup, and in many respects, it has delivered. Comprehensive genomic profiling (CGP) has driven much of this progress, enabling clinicians to sequence hundreds of cancer-related genes at once and identify mutations that can be paired with treatment. However, these benefits remain unevenly distributed across cancer types. Patients with relatively rare cancers are less likely to receive genomically matched treatment than those with more common cancers, even when CGP identifies an actionable mutation. This blog examines why that gap exists and the strategies that could help close it.
The Precision Oncology Divide
The ability to identify genomic variants has powered precision oncology, allowing clinicians to connect specific mutations to targeted therapies quickly enough to influence treatment decisions. Technologies such as CGP function as key companion diagnostic assays, sequencing hundreds of cancer-related genes and enabling more precise treatment choices for each patient. Although precision oncology has delivered substantial benefits for many cancer types, some cancers, particularly rarer ones, have seen far less impact from these approaches.
A systematic review of 14 CGP studies involving 35,975 patients showed that CGP-guided treatment improved overall survival and progression-free survival across cancer types, but patients with rare cancers were less likely to receive a genomically matched therapy than those with more common cancers1. A separate study found stark differences across cancer types in how often CGP results led to an approved or experimental biomarker-linked therapy. Lung cancer, the most commonly diagnosed cancer worldwide, saw roughly 20% of patients receive matched treatment, compared to just 2% for pancreatic cancer, the 11th most common2. While pancreatic cancer is not classified as a rare cancer, this finding highlights a gap in therapeutic benefit between cancer types and underscores how the limited maturity of targeted therapies for pancreatic tumors remains a barrier to more personalized care.
Why Rare Cancers Fall Further Behind
Despite this documented benefit, only around 8% of patients currently receive CGP‑guided biomarker-linked therapy, indicating that broader CGP access is needed not only to narrow the rare cancer treatment gap but also to improve outcomes across cancer types more generally. A systematic review of 14 CGP studies found that 40-94% of patients had at least one clinically actionable alteration identified by CGP1, highlighting that barriers beyond test access, such as therapy availability, interpretation, and workflow, also drive the disconnect between genomic insights and real-world treatment.
Increased CGP testing alone is not enough to close the gap between genomic results and real-world treatment. Most CGP reports do not explicitly rank or prioritize which targetable mutations have the strongest clinical evidence. In the absence of standardized frameworks, different clinicians may interpret the same findings differently, meaning some patients may never be offered a potentially effective targeted therapy. Compounding this, there is still no uniform guidance on which tumor types should routinely receive CGP, so decisions about whether to test are often left to individual clinical teams, introducing further inconsistency. When CGP is performed, clinicians must often manually judge which alterations are truly actionable, adding workload to already stretched teams and increasing the risk that a clinically meaningful, possibly life‑changing mutation is missed simply due to limited time and resources.
Closing the Gap
Closing the rare cancer treatment gap will require more than simply ordering CGP more often. It will require changes in how results are interpreted, acted on, and shared across systems.
Molecular Tumor Boards
A minority of CGP studies make use of the insights of a molecular tumor board (MTB), a multidisciplinary panel of oncologists, geneticists, pathologists, and pharmacologists who convene to review a patient’s genomic profile and collectively recommend the most clinically appropriate, evidence-supported treatment option. Importantly, in studies where MTB review was used, patients consistently had better outcomes than when treatment decisions were made independently by individual physicians, underscoring that expert, structured interpretation may be just as critical to closing the treatment gap as access to the test itself1.
Tumor Agnostic Biomarkers
A promising way to narrow this gap is to focus on tumor‑agnostic biomarkers that can be directly linked to specific treatments, regardless of where the cancer originates. Examples include global tumor mutational burden and microsatellite instability status, both already used to guide pan‑tumor immunotherapy approvals2. By anchoring decisions to these molecular features rather than anatomical sites, CGP‑derived biomarkers can extend targeted options to patients with rare cancers, helping them access therapies even when tumor‑specific approvals for their cancer type do not yet exist.
Liquid Biopsies and Additional Analyses
Another promising way to expand CGP’s value in rare cancers is through more accessible biomarkers. Liquid biopsies can capture circulating tumor cells and circulating tumor DNA, enabling CGP when tissue is scarce or difficult to obtain. Combining CGP with additional analyses can also increase the yield of actionable findings from tumor samples. For instance, integrating transcriptomic profiling links genomic mutations to gene expression patterns and provides richer biological context, making it easier to translate genomic insights into concrete treatment decisions.
Global Data-Sharing and Harmonized Knowledgebases
Today, variant interpretation is spread across multiple, partially overlapping databases, so clinicians have no single, unified reference for assessing genomic findings. Mutations from rare cancers are less likely to be comprehensively represented in all of these resources, increasing the risk that a clinician using one database may miss a potential targeted option that appears in another. Aggregating CGP results into harmonized, shared knowledgebases would enable more powerful analyses and help reveal cross‑tumor patterns in rarer cancers, improving variant interpretation and supporting more informed, evidence‑based treatment decisions.
Conclusion
Broader CGP access is a critical step toward closing the rare cancer treatment gap, but it is not the whole story. As more patients are tested, CGP will continue to uncover a high proportion of clinically actionable alterations, with systematic data suggesting rates as high as 94%. However, only a small minority currently receive genomically matched therapy. Without parallel investment in downstream interpretation and treatment pathways, including molecular tumor boards, standardized evidence‑tiering for variants, and more reliable access to matched drugs and trials, expanded testing will mostly increase the number of unrealized opportunities rather than consistently translating findings into better outcomes. Access to robust CGP analyses, particularly those integrating genomic alterations with transcriptome data, will expand the pool of clinically relevant biomarkers and increase the likelihood that patients with rare cancers can be matched to effective therapies and trials.
Reach out to Sampled’s experts to learn more about CGP and how it can be combined with additional omic layers in our CLIA‑licensed, CAP‑accredited fully integrated analytical laboratory and biorepository.
References
1. Limaye S, Deshmukh J, Rohatagi N, et al. Usefulness of Comprehensive Genomic Profiling in Clinical Decision-Making in Oncology: A Systematic Review. J Immunother Precis Oncol. 2025;8(1):55-63. doi:10.36401/JIPO-24-11
2. Saito Y, Horie S, Kogure Y, et al. Real-world clinical utility of comprehensive genomic profiling in advanced solid tumors. Nat Med. 2026;32(2):690-701. doi:10.1038/s41591-025-04086-8
