Precision/personalized medicine implements interrogation of genomic/transcriptomic/proteomic/immunomic (multi-omic) tumor/patient profiles and gene/immune-targeted drug deployment. As a result, the outlook for several lethal cancers is being transformed. For example, there are now several FDA-approved medications that target the sequelae of altered genes in a tumor-agnostic approach including, but not limited to pembrolizumab [microsatellite instability and tumor mutational burden (TMB) ≥10 mutations/megabase (mut/Mb)] and larotrectinib/entrectinib (NTRK fusions). Multi-omic analysis further unveils the disruptive reality that metastatic cancers are tremendously complicated and individually distinct. As a result, optimized treatment often requires drug combinations (rather than scripted monotherapies) and N-of-one customization. In order to fully operationalize multi-matched drug combinations, doses must also be individualized. Early studies of this strategy confirm feasibility, safety, and efficacy. Real-world data/master registry trials may also provide massive, clinically relevant datasets that further fuel a revolution in cancer care. Finally, advanced bioinformatic technology can assist in deciphering complex altered cancer pathways in individual patients and help with matching their tumors to an optimized combination of cytotoxics, targeted drugs, hormonal therapies and immunotherapies.
Rare and ultra-rare cancers, which are by definition, individually uncommon, comprise about 25% of the cancer burden. They are not only a large unmet need, as patients have few approved or clinical trial options, but also serve as a unique model for a personalized/precision approach to common cancers, ultimately leading to the strategy that recognizes each patient/tumor as an N-of-1.