# MYC

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

## TL;DR

MYC is the most commonly amplified cancer gene, a master switch that turns on thousands of growth genes. It has no pocket for a conventional drug, so it remained 'undruggable' for 40 years; the first direct MYC drugs finally entered trials in the 2020s.

## Summary

MYC family transcription factors (MYC, MYCN, MYCL) dimerise with MAX to drive ribosome biogenesis, metabolism, and proliferation; deregulated in >50% of cancers via amplification, translocation (Burkitt), or upstream signalling (Wnt, RAS, Notch). MYC also suppresses immune recognition (CD47, PD-L1). Direct approaches: OMO-103 (Omomyc mini-protein, phase 1/2 in PDAC), MYC degraders, and MAX-stabilising molecules; indirect: CDK9 and BET inhibitors that reduce MYC transcription, PLK1 and AURKA inhibitors that destabilise MYC/MYCN protein (neuroblastoma), and synthetic-lethal dependencies (mTOR, splicing).

## Fields

- Kind: Pathway
- Last checked: 2026-09-08
- Tags: mechanism
- Analogy: A conductor who can make every section of the orchestra play louder at once. You cannot take away the baton, so drugs try to silence the score (transcription), tire the conductor (degradation), or exploit the fact that a full-volume orchestra cannot afford a single missing player.
- Interventions: OMO-103 (Omomyc) phase 1/2 in pancreatic cancer; BET and CDK9 inhibitors reduce MYC transcription (haematologic trials); AURKA inhibitors in MYCN-amplified neuroblastoma; MYC-driven dependencies: mTOR, spliceosome, glutamine

## Notes

- Leading programmes: Soucek (VHIO, Omomyc/Peptomyc); Felsher (Stanford, MYC addiction); Eilers (Würzburg); Dang (Ludwig); Bradner/Vakoc (CSHL, BET inhibitors).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Myc
- Dhanasekaran et al., The MYC oncogene: the grand orchestrator of cancer growth and immune evasion (Nature Reviews Clinical Oncology 2022): https://doi.org/10.1038/s41571-021-00549-2
- OMO-103 first-in-human (Nature Medicine 2024): https://doi.org/10.1038/s41591-024-02875-1

## Connected records

- cancers: [Atypical teratoid/rhabdoid tumour (ATRT)](https://onco.cc/cancers/atrt/), [Burkitt lymphoma](https://onco.cc/cancers/burkitt-lymphoma/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Group 3 and group 4 medulloblastoma (non-WNT/non-SHH)](https://onco.cc/cancers/medulloblastoma-group-3-4/), [High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma)](https://onco.cc/cancers/high-grade-b-cell-lymphoma-myc-bcl2/), [HIV-associated (AIDS-related) lymphomas](https://onco.cc/cancers/hiv-associated-lymphoma/), [Neuroblastoma (paediatric)](https://onco.cc/cancers/neuroblastoma/), [Neuroendocrine and small-cell prostate cancer](https://onco.cc/cancers/prostate-nepc/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [NUT carcinoma (midline carcinoma with NUTM1 rearrangement)](https://onco.cc/cancers/nut-carcinoma/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Plasmablastic lymphoma](https://onco.cc/cancers/plasmablastic-lymphoma/), [Richter transformation of chronic lymphocytic leukaemia](https://onco.cc/cancers/richter-transformation-cll/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- targets: [AURKA](https://onco.cc/targets/aurka/), [BCL-2](https://onco.cc/targets/bcl2/), [BCL6](https://onco.cc/targets/bcl6/), [BRD4](https://onco.cc/targets/brd4/), [CD47](https://onco.cc/targets/cd47/), [CDK9](https://onco.cc/targets/cdk9/), [IKZF1 (Ikaros)](https://onco.cc/targets/ikzf1/), [IRF4](https://onco.cc/targets/irf4/), [KRAS](https://onco.cc/targets/kras/), [MAX](https://onco.cc/targets/max/), [MYC](https://onco.cc/targets/myc-gene/), [PLK1](https://onco.cc/targets/plk1/)
- institutions: [Cold Spring Harbor Laboratory](https://onco.cc/institutions/cold-spring-harbor/), [Dana-Farber Brigham Cancer Center](https://onco.cc/institutions/dana-farber/), [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: [Cancer metabolism](https://onco.cc/pathways/cancer-metabolism/), [Circadian control](https://onco.cc/pathways/circadian-control/), [DNA replication & origin licensing](https://onco.cc/pathways/dna-replication-licensing/), [DNA replication stress](https://onco.cc/pathways/replication-stress/), [Glutamine addiction](https://onco.cc/pathways/glutamine-metabolism/), [mRNA translation (eIF4F / mTOR)](https://onco.cc/pathways/mrna-translation-eif4f/), [Myeloid suppression: TAMs, MDSCs & don't-eat-me signals](https://onco.cc/pathways/myeloid-suppression-axis/), [Notch signalling](https://onco.cc/pathways/notch/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [RNA splicing](https://onco.cc/pathways/rna-splicing/), [The germinal centre reaction](https://onco.cc/pathways/germinal-centre-reaction/), [Transcriptional machinery & addiction](https://onco.cc/pathways/transcription-addiction/), [Ubiquitin-proteasome system & protein homeostasis](https://onco.cc/pathways/ubiquitin-proteasome-system/), [Wnt / β-catenin](https://onco.cc/pathways/wnt/)
- terms: [Double-hit / high-grade B-cell lymphoma](https://onco.cc/terms/double-hit-lymphoma/), [Hallmark: sustaining proliferative signalling](https://onco.cc/terms/sustaining-proliferative-signaling/), [MYCN amplification](https://onco.cc/terms/mycn-amplification/), [Tumour-associated macrophages (TAMs)](https://onco.cc/terms/tumor-associated-macrophages/)
- key papers: [A sarcoma involving the jaws in African children](https://onco.cc/key-papers/paper-burkitt-sarcoma-involving-jaws-african-children-br-j-surg-1958/), [A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-hayashi-squamous-basal-like-pancreatic-nat-cancer-2020/), [Comprehensive molecular characterization of human colon and rectal cancer](https://onco.cc/key-papers/paper-tcga-colorectal-comprehensive-characterization-nature-2012/), [Comprehensive molecular portraits of human breast tumours](https://onco.cc/key-papers/paper-tcga-breast-molecular-portraits-nature-2012/), [Locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial](https://onco.cc/key-papers/paper-brown-nat-med/), [Loss of KDM6A activates super-enhancers to induce gender-specific squamous-like pancreatic cancer and confers sensitivity to BET inhibitors](https://onco.cc/key-papers/paper-andricovich-kdm6a-squamous-pancreatic-cancer-cell-2018/), [Molecular characterisation of neuroendocrine prostate cancer and identification of new drug targets](https://onco.cc/key-papers/paper-beltran-nepc-aurka-mycn-cancer-discov-2011/), [Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data](https://onco.cc/key-papers/paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019/), [MYC pathway activation in triple-negative breast cancer is synthetic lethal with CDK inhibition](https://onco.cc/key-papers/paper-horiuchi-myc-tnbc-cdk-synthetic-lethal-jem-2012/), [Oncogenic genomic alterations, clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer](https://onco.cc/key-papers/paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020/), [The consensus molecular subtypes of colorectal cancer](https://onco.cc/key-papers/paper-cms-guinney-nat-med-2015/), [The MYC oncogene - the grand orchestrator of cancer growth and immune evasion](https://onco.cc/key-papers/paper-dhanasekaran-nat-rev-clin-oncol/), [The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma](https://onco.cc/key-papers/paper-rosenwald-molecular-profiling-dlbcl-nejm-2002/), [Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis](https://onco.cc/key-papers/paper-bareche-tnbc-multiomic-heterogeneity-ann-oncol-2018/), [Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets](https://onco.cc/key-papers/paper-witkiewicz-pancreatic-exomes-utsw-nat-commun-2015/)
- biomarkers: [Double expressor: MYC and BCL2 protein together by immunohistochemistry](https://onco.cc/biomarkers/myc-bcl2-double-expressor/), [Double-hit and triple-hit: MYC with BCL2 and BCL6 rearrangement](https://onco.cc/biomarkers/double-hit-rearrangement/)
- roadmaps: [Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome](https://onco.cc/roadmaps/epigenetics-roadmap/), [Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting](https://onco.cc/roadmaps/lymphoma-roadmap/), [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)
- ideas: [Can MYC be drugged directly, and will patients tolerate it?](https://onco.cc/ideas/idea-drugging-myc/)

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JSON: https://onco.cc/api/v1/entities/myc.json