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A tumour is a population that evolves by natural selection. Treatment kills the sensitive cells and selects the rest, which is why resistance is the rule; measuring the surviving population (MRD) and adapting therapy is the counter-strategy.
Truncal mutations are shared by all cells; branched subclones carry private alterations (TRACERx, PCAWG). Therapy imposes selection: pre-existing resistant clones (EGFR T790M, ESR1) expand, or drug-tolerant persisters acquire mutations later. Neutral and punctuated evolution, whole-genome doubling, and CIN modulate the tempo. ctDNA lets clonal dynamics be followed in real time; MRD detection after curative therapy identifies who will relapse. Adaptive therapy (dose modulation to maintain sensitive competitors, Moffitt prostate pilot) and combination strategies aim to steer rather than merely suppress evolution.
Clonal evolution is like weeding a field with one herbicide year after year: the field fills with the one weed that shrugs it off. Rotating herbicides and leaving some susceptible weeds to crowd out the resistant ones is the evolutionary alternative.
Relapse after surgery is driven by particular subclones that can be identified in the primary tumour and tracked in blood, which argues for evolution-aware adjuvant strategies. The pollution finding reframes carcinogenesis: some agents promote already-mutant cells rather than causing mutations.
Lung cancer in never-smokers is not smokers' lung cancer with the smoking removed; it is a different set of diseases with a different clock. The slow-growing piano subtype in particular is the argument that a screening test aimed at never-smokers would need to look for something other than what low-dose computed tomography was built to find.
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 gives surveillance a target and a timetable: catch high-grade dysplasia and there are about three years before invasion, and TGF-beta pathway loss is the event to detect.
It splits the alterations into two groups with different practical meanings. The repair defects are present at diagnosis at close to their castration-resistant prevalence, so testing early is worthwhile; AR, TP53 and RB1 changes accumulate later, so a diagnostic sample does not answer questions about the disease in front of you at relapse.
It explains why single-sample classifiers disagree on about one tumour in eight and why KRAS allelic imbalance and GATA6 copy number are being read alongside expression.
It gives the sequencing report a prognostic reading that does not depend on a repeat biopsy: an EGFR-mutant cancer that also carries RB1 and TP53 alterations will stop responding sooner and should be watched for a change of histology.
Re-biopsy and re-sequencing at relapse can find repair defects and a higher mutation burden that the primary did not show, which matters for PARP inhibitor and immunotherapy eligibility in metastatic TNBC.
Shares Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer, The mutational landscape of lethal castration-resistant prostate cancer, Cancer stem cells & phenotypic plasticity, Drug-tolerant persister cells and the tag mechanism.
Shares Kill drug-tolerant persisters through ferroptosis, Drug-tolerant persister cells, Broad Institute of MIT and Harvard, Drug resistance (primary and acquired) 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 Attack extrachromosomal DNA, the engine of oncogene amplification, The Francis Crick Institute, Chromosomal instability & aneuploidy, TP53 and the tag mechanism.
Shares Genomic characterization of malignant progression in neoplastic pancreatic cysts, Tumour dormancy, The metastatic cascade, Memorial Sloan Kettering Cancer Center and the tag mechanism.
Shares A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma, Richter transformation of chronic lymphocytic leukaemia, Non-Hodgkin lymphoma (all types), Pancreatic ductal adenocarcinoma and the tag mechanism.
Shares The metastatic cascade, Memorial Sloan Kettering Cancer Center, Pancreatic ductal adenocarcinoma, Prostate cancer and the tag mechanism.
Shares The metastatic cascade, Theories of cancer: how the ideas connect, Memorial Sloan Kettering Cancer Center, Non-Hodgkin lymphoma (all types) and the tag mechanism.