# Starve MYC-driven tumours by blocking protein production machinery

Source: https://onco.cc/ideas/idea-bio1-translation-dependency-myc/  
OnCo record `idea-bio1-translation-dependency-myc` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Cancers driven by MYC need to make proteins at an unusually fast rate. Slowing the cell's protein factory hits them harder than it hits normal cells.

## Summary

MYC amplification imposes dependence on cap-dependent translation, ribosome biogenesis and eIF4A/eIF4E activity. Selective eIF4A inhibitors (for example zotatifin) and RNA polymerase I inhibitors have entered clinical trials. Rather than treating these as broad cytotoxics, the proposal is to select patients by MYC amplification or a translation-dependency signature, which has not been done systematically.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Response to eIF4A or ribosome biogenesis inhibition is concentrated in tumours with MYC amplification or a high translation-dependency signature, with a response rate at least three times that of unselected patients.
- Rationale: Blocking translation is an indirect route to MYC that requires no MYC binder; the dependency is well supported in models, but trials to date have largely been unselected, which is a common reason such drugs fail.
- Proposed test: Biomarker-stratified phase 2 with pre-specified MYC-amplified and signature-high cohorts, powered to compare response rates between strata.
- Maturity: early-clinical
- Actor: industry

## Sources

- Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017): https://doi.org/10.1038/nrc.2017.36

## Connected records

- cancers: [Small-cell lung cancer](https://onco.cc/cancers/sclc/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- terms: [Oncogene addiction](https://onco.cc/terms/oncogene-addiction/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)
- key papers: [Drugging the 'undruggable' cancer targets](https://onco.cc/key-papers/paper-dang-nat-rev-cancer/)

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