Molecularly profiled trials: toward a framework of actions for the "nil actionables"

Br J Cancer. 2021 Aug;125(4):473-478. doi: 10.1038/s41416-021-01423-9. Epub 2021 May 26.

Abstract

The sequencing of tumour or blood samples is increasingly used to stratify patients into clinical trials of molecularly targeted agents, and this approach has frequently demonstrated clinical benefit for those who are deemed eligible. But what of those who have no clear and evident molecular driver? What of those deemed to have "nil actionable" mutations? How might we deliver better therapeutic opportunities for those left behind in the clamour toward stratified therapeutics? And what significant learnings lie hidden in the data we amass but do not interrogate and understand? This Perspective article suggests a holistic approach to the future treatment of such patients, and sets a framework through which significant additional patient benefit might be achieved. In order to deliver upon this framework, it encourages and invites the clinical community to engage more enthusiastically and share learnings with colleagues in the early drug discovery community, in order to deliver a step change in patient care.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adenocarcinoma of Lung / drug therapy*
  • Adenocarcinoma of Lung / genetics
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Clinical Decision-Making
  • Disease Progression
  • Female
  • GTP Phosphohydrolases / genetics*
  • Humans
  • Membrane Proteins / genetics*
  • Middle Aged
  • Molecular Targeted Therapy
  • Mutation*
  • Precision Medicine

Substances

  • Antineoplastic Agents
  • Membrane Proteins
  • GTP Phosphohydrolases
  • NRAS protein, human