{"entity":{"id":"idea-bio1-translation-dependency-myc","kind":"idea","name":"Starve MYC-driven tumours by blocking protein production machinery","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":["sclc","tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["oncogene-addiction"],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-biomarker-validation"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"medium","horizonYears":4},"route":"/ideas/idea-bio1-translation-dependency-myc/","neighbours":{"cancer":[{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"term":[{"id":"oncogene-addiction","kind":"term","name":"Oncogene addiction","route":"/terms/oncogene-addiction/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"paper":[{"id":"paper-dang-nat-rev-cancer","kind":"paper","name":"Drugging the 'undruggable' cancer targets","route":"/key-papers/paper-dang-nat-rev-cancer/"}]}}