{"entity":{"id":"idea-drugging-myc","kind":"idea","name":"Can MYC be drugged directly, and will patients tolerate it?","aka":[],"tldr":"MYC drives half of all cancers but has no pocket for a drug and is needed by normal cells too. The first direct MYC blockers are in trials; the question is whether there is a therapeutic window.","summary":"This open question asks whether MYC can be drugged directly and tolerated: MYC drives half of all cancers but has no pocket for a drug and is needed by normal cells too. OMO-103 (Omomyc) showed safety and disease stabilisation in phase 1, and mouse studies showed reversible toxicity in proliferating tissues, but human tolerance at effective doses is unproven. The hypothesis is that transient, intermittent MYC inhibition achieves regression in MYC-amplified cancers while normal tissues recover between doses, and PD-1 blockade may add benefit via CD47 and PD-L1. The test is a randomised phase 2 of OMO-103 plus chemotherapy in MYC-amplified Pancreatic ductal adenocarcinoma and Triple-negative breast cancer (TNBC).","asOf":"2026-09-08","links":[{"label":"Garralda et al., MYC targeting by OMO-103 in solid tumours: a phase 1 trial (Nature Medicine 2024)","url":"https://doi.org/10.1038/s41591-024-02805-1"}],"tags":["mechanism","open-question"],"related":[],"cancers":["pancreatic","tnbc","neuroblastoma"],"sections":[],"technologies":[],"targets":["cd47"],"drugs":[],"companies":[],"institutions":["vall-dhebron","ucsf"],"pathways":["myc"],"terms":[],"trials":["nct05482893"],"people":[],"bottlenecks":[],"keyPapers":["paper-garralda-nat-med","paper-cd47-pancreatic-pharmacol-res-2022","paper-cd47-neuroblastoma-curr-oncol-2024"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Transient, incomplete MYC inhibition (intermittent dosing) achieves tumour regression in MYC-amplified cancers while normal tissues recover between doses, yielding a usable therapeutic index.","rationale":"Soucek's Omomyc mouse models tolerated systemic MYC inhibition; MYC-addicted tumours show non-oncogene addiction to MYC dosage; combination with PD-1 blockade may add via CD47/PD-L1 downregulation.","test":"Phase 2 randomised OMO-103 plus chemotherapy vs chemotherapy in MYC-amplified metastatic PDAC and TNBC with intermittent schedules; pharmacodynamic MYC target-gene signatures in paired biopsies.","maturity":"early-clinical"},"route":"/ideas/idea-drugging-myc/","neighbours":{"cancer":[{"id":"neuroblastoma","kind":"cancer","name":"Neuroblastoma (paediatric)","route":"/cancers/neuroblastoma/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"target":[{"id":"cd47","kind":"target","name":"CD47","route":"/targets/cd47/"}],"institution":[{"id":"ucsf","kind":"institution","name":"UCSF Helen Diller Family Comprehensive Cancer Center","route":"/institutions/ucsf/"},{"id":"vall-dhebron","kind":"institution","name":"Vall d'Hebron University Hospital / VHIO","route":"/institutions/vall-dhebron/"}],"pathway":[{"id":"myc","kind":"pathway","name":"MYC","route":"/pathways/myc/"}],"trial":[{"id":"nct05482893","kind":"trial","name":"Spevatamig (PT886) as Monotherapy or in Combination With Chemo and/or ICI, for the Treatment of Patients With Advanced Gastric, Gastroesophageal Junct","route":"/trials/nct05482893/"}],"paper":[{"id":"paper-cd47-neuroblastoma-curr-oncol-2024","kind":"paper","name":"A Perspective on the CD47-SIRPA Axis in High-Risk Neuroblastoma","route":"/key-papers/paper-cd47-neuroblastoma-curr-oncol-2024/"},{"id":"paper-garralda-nat-med","kind":"paper","name":"MYC targeting by OMO-103 in solid tumors: a phase 1 trial","route":"/key-papers/paper-garralda-nat-med/"},{"id":"paper-cd47-pancreatic-pharmacol-res-2022","kind":"paper","name":"Overcoming immunotherapeutic resistance in PDAC: SIRPα-CD47 blockade","route":"/key-papers/paper-cd47-pancreatic-pharmacol-res-2022/"}]}}