# Can MYC be drugged directly, and will patients tolerate it?

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

## TL;DR

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).

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Tags: mechanism; open-question
- 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.
- Proposed 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

## Sources

- Garralda et al., MYC targeting by OMO-103 in solid tumours: a phase 1 trial (Nature Medicine 2024): https://doi.org/10.1038/s41591-024-02805-1

## Connected records

- cancers: [Neuroblastoma (paediatric)](https://onco.cc/cancers/neuroblastoma/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- targets: [CD47](https://onco.cc/targets/cd47/)
- institutions: [UCSF Helen Diller Family Comprehensive Cancer Center](https://onco.cc/institutions/ucsf/), [Vall d'Hebron University Hospital / VHIO](https://onco.cc/institutions/vall-dhebron/)
- pathways: [MYC](https://onco.cc/pathways/myc/)
- trials: [Spevatamig (PT886) as Monotherapy or in Combination With Chemo and/or ICI, for the Treatment of Patients With Advanced Gastric, Gastroesophageal Junct](https://onco.cc/trials/nct05482893/)
- key papers: [A Perspective on the CD47-SIRPA Axis in High-Risk Neuroblastoma](https://onco.cc/key-papers/paper-cd47-neuroblastoma-curr-oncol-2024/), [MYC targeting by OMO-103 in solid tumors: a phase 1 trial](https://onco.cc/key-papers/paper-garralda-nat-med/), [Overcoming immunotherapeutic resistance in PDAC: SIRPα-CD47 blockade](https://onco.cc/key-papers/paper-cd47-pancreatic-pharmacol-res-2022/)

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