Restoring Cancer Genomes: Functional Mutation Correction as a Platform for Precision Oncology

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Contributors

Abstract

Cancer genome sequencing has uncovered an extensive landscape of somatic mutations. However, determining which of these alterations are biologically consequential and therapeutically actionable remains a central challenge in oncology. CRISPR-based genome editing now enables precise correction of oncogenic mutations within their endogenous genomic context. Recent work demonstrates that repairing cancer hotspot mutations restores conserved tumor-relevant transcriptional programs across diverse tumor types, revealing tumor-agnostic dependencies. Beyond therapeutic implications, this mutation-correction framework provides a scalable functional platform to stratify drivers, interrogate variants of uncertain significance, and refine precision diagnostics. This perspective discusses how programmable mutation correction advances (i) mechanistic cancer biology, (ii) personalized cancer diagnostics, and (iii) next-generation precision gene therapies. We propose that systematic reversal of cancer mutations represents a conceptual shift from observing mutational landscapes to actively testing their biological necessity.

Details

Original languageEnglish
Pages (from-to)663-669
Number of pages7
JournalHuman gene therapy
Volume37
Issue number15-16
Publication statusE-pub ahead of print - 27 Jul 2026
Peer-reviewedYes

External IDs

PubMed 42504876

Keywords

Sustainable Development Goals

Keywords

  • base editing, cancer, driver mutation, mutation repair, p53