'Latent drivers' expand the cancer mutational landscape

Ruth Nussinov*, Chung Jung Tsai

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

A major challenge facing the community involves identification of mutations that drive cancer. Analyses of cancer genomes to detect, and distinguish, 'driver' from 'passenger' mutations are daunting tasks. Here we suggest that there is a third 'latent driver' category. 'Latent driver' mutations behave as passengers, and do not confer a cancer hallmark. However, coupled with other emerging mutations, they drive cancer development and drug resistance. 'Latent drivers' emerge prior to and during cancer evolution. These allosteric mutations can work through 'AND' all-or-none or incremental 'Graded' logic gate mechanisms. Current diagnostic platforms generally assume that actionable 'driver' mutations are those appearing most frequently in cancer. We propose that 'latent driver' detection may help forecast cancer progression and modify personalized drug regimes.

Original languageEnglish
Pages (from-to)25-32
Number of pages8
JournalCurrent Opinion in Structural Biology
Volume32
DOIs
StatePublished - 1 Jun 2015

Funding

FundersFunder number
Center for Cancer Research
National Institutes of HealthHHSN261200800001E
National Cancer InstituteZIABC010442

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