Cancer of unknown primary (CUP) is a diagnosis given when cancer has spread (metastasised) but the original site where it began — the primary — cannot be identified, even after extensive investigation.
Unlike most cancers, which are named and treated based on where they start (breast, lung, colon), CUP is defined by the absence of that information. This makes it an outlier in modern oncology, where treatment strategies are built around tissue-of-origin.
CUP accounts for 1–3% of all cancer diagnoses, making it one of the ten most common cancers. Yet it receives a fraction of the research attention and funding of far rarer diseases.
Standard-of-care remains platinum-based chemotherapy — an approach that has not meaningfully changed in over twenty years. The primary focus has been on improving tissue-of-origin identification, with the hope that site-specific therapy will improve survival. But the lack of conclusive evidence to support this approach has reignited debate about whether identifying the primary is even the right strategy.
Efforts to address CUP have focused on diagnosis rather than treatment. Here is the current state of the field.
Companies like Veracyte and Foundation Medicine offer genomic profiling to classify CUP patients so they can be funnelled into existing site-specific treatment pathways. These are diagnostic plays — they don't develop drugs for CUP itself.
The most significant clinical effort to date — a randomised trial evaluating molecularly-guided therapy in CUP patients with actionable mutations. Results showed benefit for ~32% of patients, but explicitly does not address the ~68% without targetable alterations.
Groups at The Christie (Manchester) and Sarah Cannon Research Institute have run CUP-focused clinical studies. These are academic research programmes — important work, but not company-level drug development efforts.
There is no biotech or pharmaceutical company anywhere in the world with CUP as its primary disease focus or lead therapeutic indication. This is the white space Phantom Therapeutics was built to fill.
Phantom Therapeutics is building a platform designed for the patients the current paradigm leaves behind.