From Tissue-Agnostic to N-of-One Therapies: (R)Evolution of the Precision Paradigm

Jacob J. Adashek, Vivek Subbiah, Razelle Kurzrock

Research output: Contribution to journalReview articlepeer-review


Precision medicine has exploited next-generation sequencing (NGS) and gene/immune-targeted drug deployment to transform the outlook for several lethal cancers. For instance, there are now several FDA-approved medications that target the sequelae of aberrant genes in a tissue-agnostic approach: pembrolizumab [microsatellite instability and tumor mutational burden (TMB) ≥10 mutations/megabase (mut/Mb)] and larotrectinib/entrectinib (NTRK fusions). Molecular interrogation further reveals the disruptive reality that metastatic cancers are tremendously complex and individually distinct. Therefore, optimized treatment often requires drug combinations (rather than monotherapy) and N-of-one customization. Early studies of this approach suggest feasibility, safety, and efficacy. Real-world data/master registry trials may also provide massive, clinically relevant datasets that further fuel the (r)evolution in oncology.

Original languageEnglish (US)
Pages (from-to)15-28
Number of pages14
JournalTrends in Cancer
Issue number1
StatePublished - Jan 2021


  • cancer genes
  • cell-free DNA
  • circulating tumor DNA
  • next-generation sequencing
  • precision oncology

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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