Developing Drugs for Tissue-Agnostic Indications: A Paradigm Shift in Leveraging Cancer Biology for Precision Medicine

Nathan D. Seligson, Todd C. Knepper, Susanne Ragg, Christine M. Walko

Research output: Contribution to journalReview article

Abstract

Targeted therapies have reshaped the landscape of the development of cancer therapeutics. Recent biomarker-driven, tissue-agnostic clinical trials represent a significant paradigm shift in precision cancer medicine. Despite their growth in preclinical and clinical studies, to date only a few biomarker-driven, tissue-agnostic indications have seen approval by the US Food and Drug Administration (FDA). These approvals include pembrolizumab in microsatellite instability-high or mismatch repair deficient solid tumors, as well as both larotrectinib and entrectinib in NTRK fusion-positive tumors. Complex cancer biology, clinical trial design, and identification of resistance mechanisms represent some of the challenges that future tissue-agnostic therapies have to overcome. In this Review, we present a brief history of the development of tissue-agnostic therapies, comparing the similarities in the approval of pembrolizumab, larotrectinib, and entrectinib for tissue-agnostic indications. We also explore the future of tissue-agnostic cancer therapeutics while identifying important challenges for the future that drugs targeting tissue-agnostic indications will face.

Original languageEnglish (US)
JournalClinical Pharmacology and Therapeutics
DOIs
StateAccepted/In press - 2020
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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