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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.
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).
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.
One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
It joins the pathology (adenosquamous), the transcriptome (basal-like) and the genome (KDM6A, MYC) into one account of the chemotherapy-resistant subtype, and shows a single biopsy can miss it.
It fills the gap between the primary-tumour atlases and the castration-resistant series by describing the disease at the moment most treatment decisions are actually made, and it identifies SPOP as a favourable marker rather than a neutral one.
The organising framework for every small-cell lung cancer trial designed since. It is also why the slow progress in the disease is now attributed to treating four diseases as one rather than to the biology being intractable.
It gives the 3 to 4% of KDM6A-mutant, squamous-programme tumours a mechanism and a candidate drug class.
This is the sourced bridge between expression subtype and mutation: it tells a clinician that a LAR tumour is the one to sequence for PIK3CA and AKT1, and that immunomodulatory biology is a favourable prognostic group before any immunotherapy.
The CMS framework organises colorectal cancer biology and trial stratification; BRAF V600E tumours cluster in CMS1, and CMS4's shorter survival and stromal signalling are targets of ongoing research.
Shares Loss of KDM6A activates super-enhancers to induce gender-specific squamous-like pancreatic cancer and confers sensitivity to BET inhibitors, BRD4, The germinal centre reaction, NUT carcinoma (midline carcinoma with NUTM1 rearrangement) and the tag mechanism.
Shares A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma, DNA replication stress, Atypical teratoid/rhabdoid tumour (ATRT), Transcriptional machinery & addiction and the tag mechanism.
Shares Tumour-associated macrophages (TAMs), CD47, Cold Spring Harbor Laboratory, Myeloid suppression: TAMs, MDSCs & don't-eat-me signals and the tag mechanism.
Shares Cold Spring Harbor Laboratory, Cancer metabolism, RAS / RAF / MEK / ERK (MAPK), KRAS and the tag mechanism.
Shares Notch signalling, Atypical teratoid/rhabdoid tumour (ATRT), Wnt / β-catenin, Dana-Farber Brigham Cancer Center and the tag mechanism.
Shares Glutamine addiction, Cancer metabolism, RAS / RAF / MEK / ERK (MAPK), KRAS and the tag mechanism.
Shares IRF4, Ubiquitin-proteasome system & protein homeostasis, UCSF Helen Diller Family Comprehensive Cancer Center, MYC and the tag mechanism.
Shares DNA replication stress, Comprehensive molecular characterization of human colon and rectal cancer, MYC, Pancreatic ductal adenocarcinoma and the tag mechanism.