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A machine that opens and closes DNA so genes can be read. One in five cancers has a broken part (ARID1A, SMARCA4, PBRM1), and losing one part often creates a dependence on its twin, which is the basis for new synthetic-lethal drugs.
SWI/SNF (BAF, PBAF, ncBAF) complexes remodel nucleosomes; subunits are mutated in ~20% of cancers: ARID1A (ovarian clear cell, endometrial, bladder), SMARCA4 (lung, SCCOHT), PBRM1 (clear-cell RCC), SMARCB1 (rhabdoid tumours, epithelioid sarcoma). Dependencies: SMARCA4-loss → SMARCA2 (degraders in trials), ARID1A-loss → EZH2/ATR/PARP, SMARCB1-loss → EZH2 (tazemetostat, withdrawn 2026 for safety). PBRM1 loss associates with IO response in RCC (debated). FHD-286 (BRM/BRG1 inhibitor) is in AML trials.
A librarian who unlocks shelves on request. When one librarian is fired the other covers both shifts; fire the second and the library stops working. That second librarian is the drug target.
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.
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 turned a frequently reported variant into an interpretable one: the class decides whether the stain will be negative, how poor the prognosis is, and whether immunotherapy is more rather than less likely to help.
It is the empirical basis for treating the two histologies as separate diseases for targeted therapy and as one disease for immunotherapy, which is exactly how they are treated.
With Moffitt's classical and basal-like split (the squamous and basal-like groups overlap) this fixed the molecular vocabulary of the disease and gave Precision-Panc and the UK's Glasgow group their trial framework.
The APGI cohort became the backbone of the QCMG whole-genome and subtype papers; ATM's entry here is the origin of its place on today's germline panels.
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 Cancer stem cells & phenotypic plasticity, Atypical teratoid/rhabdoid tumour (ATRT), Stanford Health Care / Stanford Cancer Institute, Dana-Farber Brigham Cancer Center and the tag mechanism.
Shares Genomic analyses identify molecular subtypes of pancreatic cancer, Cancer stem cells & phenotypic plasticity, Dana-Farber Brigham Cancer Center, Non-small-cell lung cancer and the tag mechanism.
Shares ATR, DNA replication stress, Dana-Farber Brigham Cancer Center and the tag mechanism.
Shares Epigenetic progenitor theory: cancer without a first mutation, Broad Institute of MIT and Harvard, Epigenetic reprogramming, Dana-Farber Brigham Cancer Center and the tag mechanism.
Shares DNA replication stress, Stanford Health Care / Stanford Cancer Institute, Pancreatic ductal adenocarcinoma, Colorectal cancer and the tag mechanism.
Shares A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma, Cancer stem cells & phenotypic plasticity, Broad Institute of MIT and Harvard, Pancreatic ductal adenocarcinoma and the tag mechanism.
Shares Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes, Genomic analyses identify molecular subtypes of pancreatic cancer, Pancreatic ductal adenocarcinoma, Colorectal cancer and the tag mechanism.