{"entity":{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","aka":[],"tldr":"Every tumour is a population of genetically distinct clones: in multi-region sequencing of kidney tumours, roughly two thirds of mutations were missing from at least one region. Treatment kills the dominant clones and leaves resistant minor clones to grow back, yet a single diagnostic biopsy is still treated as the whole disease.","summary":"Every cancer is a population of clones that differ by lesion, by region within a lesion, and over time. Multi-region sequencing of renal and lung tumours shows that a majority of somatic mutations are not shared by every region, so a single biopsy at diagnosis systematically under-samples the disease it is used to treat. Therapy then acts as a selection pressure: pre-existing minor subclones carrying resistance alleles expand, and new lesions can be driven by different clones from the primary. Clinical practice still assumes one genotype per patient, re-biopsies at progression are uncommon, and few trials adapt treatment to the clone that is actually growing. Longitudinal circulating tumour DNA, single-cell and spatial profiling, and evolutionary trial designs are the tools that could turn heterogeneity from an excuse into a target.","asOf":"2026-09-08","links":[{"label":"Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"},{"label":"TRACERx lung cancer evolution (Nature 2023)","url":"https://doi.org/10.1038/s41586-023-05783-5"},{"label":"McGranahan & Swanton, Clonal heterogeneity and tumor evolution (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.01.018"}],"tags":[],"related":["genie","cbioportal","idea-ctdna-switch-generalised","idea-bio1-multiregion-blocks-default","idea-bio1-rapid-autopsy-network","idea-bio1-truncal-branch-labelling","idea-bio1-outlier-lesion-biopsy","idea-bio1-barcoded-avatars-clonal-fitness","idea-bio1-evolvability-index","idea-bio1-adaptive-therapy-platform","idea-bio1-ctdna-adaptive-tki","idea-bio1-first-strike-second-strike","idea-bio1-collateral-sensitivity-atlas","idea-bio1-evolutionary-double-bind","idea-bio1-spatial-clone-immune-map","idea-bio1-methylation-clone-tracking","idea-bio1-evolution-forecasting","idea-bio1-baseline-ultradeep-resistant-clones","idea-bio1-cfrna-plasticity-tracking","idea-bio1-evolutionary-tumour-boards","idea-bio1-apobec-inhibitor-adjunct","idea-bio1-cin-vulnerability-kif18a","idea-bio1-federated-evolution-atlas","idea-bio1-clone-to-lesion-mapping","idea-bio1-rebiopsy-before-switch","idea-moon-open-cancer-cell-state-model"],"cancers":["rcc","nsclc","glioblastoma","pancreatic","breast-hr-positive"],"sections":[],"technologies":["single-cell-spatial","liquid-biopsy","cgp","wes-wgs","mrd-testing"],"targets":[],"drugs":[],"companies":["10x-genomics","guardant-health","natera"],"institutions":["francis-crick","cruk","moffitt"],"pathways":[],"terms":["resistance","ctdna","vaf","mutational-signature","oligoprogression","esr1-mutation"],"trials":["serena-6","circulate-japan"],"people":[],"bottlenecks":[],"keyPapers":["paper-mcgranahan-cell"],"journals":[],"dependsOn":[],"notes":[],"stage":"biology","severity":"critical","metrics":[{"label":"Somatic mutations not detectable across every region of a renal tumour (multi-region sequencing)","value":"63-69%","source":"Gerlinger et al., NEJM 2012","url":"https://doi.org/10.1056/NEJMoa1113205"},{"label":"Association of elevated copy-number intratumour heterogeneity with recurrence or death in resected NSCLC (TRACERx)","value":"Hazard ratio 4.9","source":"Jamal-Hanjani et al., NEJM 2017","url":"https://doi.org/10.1056/NEJMoa1616288"},{"label":"Patients and tumour regions in the TRACERx evolutionary cohort","value":"421 patients, 1,644 regions","source":"Frankell et al., Nature 2023","url":"https://doi.org/10.1038/s41586-023-05783-5"}],"causes":["Genomic instability generates diversity continuously, so any large tumour contains rare clones that are already resistant to the next drug.","A single diagnostic biopsy is treated as representative of all lesions for the whole course of disease.","Metastases are rarely biopsied, so the clones that kill patients are the least characterised.","Trials are designed around a fixed genotype and rarely re-sample or adapt treatment as clones shift.","Sequencing costs, tissue access and reimbursement rules discourage repeat and multi-region profiling."],"currentEfforts":["TRACERx (Cancer Research UK) follows hundreds of lung cancer patients with multi-region and longitudinal sequencing to map how clones evolve under treatment.","SERENA-6 showed that switching endocrine therapy on detection of an emerging ESR1 clone in ctDNA, before radiological progression, extends progression-free survival.","Single-cell and spatial transcriptomics platforms (10x Genomics and others) resolve clonal architecture within a lesion.","AACR Project GENIE and cBioPortal aggregate sequential sequencing from thousands of patients to expose recurrent evolutionary routes.","Adaptive therapy trials at Moffitt Cancer Center test dosing designed to keep sensitive clones alive so they suppress resistant ones."],"successLooksLike":"Every patient with advanced disease has serial molecular profiling (tissue or blood) that changes management, and trials routinely randomise on emerging clones rather than on the diagnostic biopsy. Resistance is anticipated and pre-empted rather than discovered on a scan."},"route":"/bottlenecks/b-tumor-heterogeneity/","neighbours":{"collection":[{"id":"genie","kind":"collection","name":"AACR Project GENIE","route":"/collections/genie/"},{"id":"cbioportal","kind":"collection","name":"cBioPortal for Cancer Genomics","route":"/collections/cbioportal/"}],"idea":[{"id":"idea-bio1-ctdna-clone-report","kind":"idea","name":"A clone report from blood at every treatment cycle","route":"/ideas/idea-bio1-ctdna-clone-report/"},{"id":"idea-bio1-adaptive-therapy-platform","kind":"idea","name":"A multi-cancer platform trial of adaptive (dose-holiday) therapy","route":"/ideas/idea-bio1-adaptive-therapy-platform/"},{"id":"idea-bio1-rapid-autopsy-network","kind":"idea","name":"A national rapid research autopsy network for end-stage cancer","route":"/ideas/idea-bio1-rapid-autopsy-network/"},{"id":"idea-bio1-evolvability-index","kind":"idea","name":"A standard evolvability score for every tumour","route":"/ideas/idea-bio1-evolvability-index/"},{"id":"idea-bio1-collateral-sensitivity-atlas","kind":"idea","name":"An open atlas of collateral sensitivity for every approved targeted drug","route":"/ideas/idea-bio1-collateral-sensitivity-atlas/"},{"id":"idea-moon-open-cancer-cell-state-model","kind":"idea","name":"An open model of every cancer cell state, built from perturbation atlases","route":"/ideas/idea-moon-open-cancer-cell-state-model/"},{"id":"idea-bio1-multiregion-blocks-default","kind":"idea","name":"Bank three spatially separate tumour blocks from every resection","route":"/ideas/idea-bio1-multiregion-blocks-default/"},{"id":"idea-bio1-barcoded-avatars-clonal-fitness","kind":"idea","name":"Barcode patient-derived tumours to watch which clones win under each drug","route":"/ideas/idea-bio1-barcoded-avatars-clonal-fitness/"},{"id":"idea-bio1-outlier-lesion-biopsy","kind":"idea","name":"Biopsy the one lesion that is growing while the others shrink","route":"/ideas/idea-bio1-outlier-lesion-biopsy/"},{"id":"idea-bio1-ctdna-adaptive-tki","kind":"idea","name":"ctDNA-guided dose holidays for lung cancer targeted therapy","route":"/ideas/idea-bio1-ctdna-adaptive-tki/"},{"id":"idea-bio1-evolutionary-double-bind","kind":"idea","name":"Design drug pairs where resisting one makes you vulnerable to the other","route":"/ideas/idea-bio1-evolutionary-double-bind/"},{"id":"idea-bio1-cfrna-plasticity-tracking","kind":"idea","name":"Detect tumours changing cell type from RNA in the blood","route":"/ideas/idea-bio1-cfrna-plasticity-tracking/"},{"id":"idea-data-digital-twin-predict-then-observe","kind":"idea","name":"Digital twins for treatment selection, validated by predicting before observing","route":"/ideas/idea-data-digital-twin-predict-then-observe/"},{"id":"idea-bio1-evolutionary-tumour-boards","kind":"idea","name":"Evolutionary tumour boards with a modeller in the room","route":"/ideas/idea-bio1-evolutionary-tumour-boards/"},{"id":"idea-bio1-drug-exposure-sanctuary-mapping","kind":"idea","name":"Find the parts of a tumour the drug never reaches","route":"/ideas/idea-bio1-drug-exposure-sanctuary-mapping/"},{"id":"idea-bio1-evolution-forecasting","kind":"idea","name":"Forecast the next resistance mutation like the weather","route":"/ideas/idea-bio1-evolution-forecasting/"},{"id":"idea-bio2-mechanism-defined-baskets","kind":"idea","name":"Group trials by broken mechanism, not by organ or single mutation","route":"/ideas/idea-bio2-mechanism-defined-baskets/"},{"id":"idea-bio1-truncal-branch-labelling","kind":"idea","name":"Label every targetable mutation as truncal or branch on the report","route":"/ideas/idea-bio1-truncal-branch-labelling/"},{"id":"idea-bio1-baseline-ultradeep-resistant-clones","kind":"idea","name":"Look for the resistant sub-population before the first dose","route":"/ideas/idea-bio1-baseline-ultradeep-resistant-clones/"},{"id":"idea-bio1-clonal-clearance-endpoint","kind":"idea","name":"Make clonal clearance, not tumour shrinkage, a trial endpoint","route":"/ideas/idea-bio1-clonal-clearance-endpoint/"},{"id":"idea-lung-resistance-directed-sequencing-at-every-progression","kind":"idea","name":"Make resistance a diagnosis: sequence at every progression and choose the next line from what the tumour became","route":"/ideas/idea-lung-resistance-directed-sequencing-at-every-progression/"},{"id":"idea-bio1-spatial-clone-immune-map","kind":"idea","name":"Map which tumour clones sit next to which immune cells before choosing therapy","route":"/ideas/idea-bio1-spatial-clone-immune-map/"},{"id":"idea-bio1-clone-to-lesion-mapping","kind":"idea","name":"Match each blood-detected clone to the lesion it comes from on the scan","route":"/ideas/idea-bio1-clone-to-lesion-mapping/"},{"id":"idea-ctdna-switch-generalised","kind":"idea","name":"Molecular-progression switching beyond ESR1","route":"/ideas/idea-ctdna-switch-generalised/"},{"id":"idea-bio1-drug-holiday-resensitisation","kind":"idea","name":"Pause a failed drug so the tumour becomes sensitive to it again","route":"/ideas/idea-bio1-drug-holiday-resensitisation/"},{"id":"idea-bio1-federated-evolution-atlas","kind":"idea","name":"Pool every multi-sample tumour genome into one open evolution atlas","route":"/ideas/idea-bio1-federated-evolution-atlas/"},{"id":"idea-bio1-antigen-mapping-at-progression","kind":"idea","name":"Re-map the tumour's surface proteins before choosing the next antibody drug","route":"/ideas/idea-bio1-antigen-mapping-at-progression/"},{"id":"idea-bio1-rebiopsy-before-switch","kind":"idea","name":"Re-test the metastasis, not the old primary, before every change of treatment","route":"/ideas/idea-bio1-rebiopsy-before-switch/"},{"id":"idea-bio1-apobec-inhibitor-adjunct","kind":"idea","name":"Slow the tumour's mutation engine with APOBEC inhibitors during targeted therapy","route":"/ideas/idea-bio1-apobec-inhibitor-adjunct/"},{"id":"idea-bio1-first-strike-second-strike","kind":"idea","name":"Switch drugs at maximum response, not at relapse","route":"/ideas/idea-bio1-first-strike-second-strike/"},{"id":"idea-bio1-methylation-clone-tracking","kind":"idea","name":"Track clones in blood with methylation patterns instead of mutations","route":"/ideas/idea-bio1-methylation-clone-tracking/"},{"id":"idea-bio1-cin-vulnerability-kif18a","kind":"idea","name":"Turn chromosomal chaos into a weakness with KIF18A inhibitors","route":"/ideas/idea-bio1-cin-vulnerability-kif18a/"},{"id":"idea-bio1-dual-antigen-adc-escape","kind":"idea","name":"Two-target antibody drugs to close the antigen escape route","route":"/ideas/idea-bio1-dual-antigen-adc-escape/"},{"id":"idea-bio2-sonobiopsy","kind":"idea","name":"Ultrasound-assisted blood test instead of a brain biopsy","route":"/ideas/idea-bio2-sonobiopsy/"},{"id":"idea-bio1-clonal-neoantigen-vaccines","kind":"idea","name":"Vaccines aimed only at mutations shared by every tumour cell","route":"/ideas/idea-bio1-clonal-neoantigen-vaccines/"},{"id":"idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine","kind":"idea","name":"Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it","route":"/ideas/idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine/"}],"cancer":[{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"},{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"company":[{"id":"10x-genomics","kind":"company","name":"10x Genomics","route":"/companies/10x-genomics/"},{"id":"guardant-health","kind":"company","name":"Guardant Health","route":"/companies/guardant-health/"},{"id":"natera","kind":"company","name":"Natera","route":"/companies/natera/"}],"institution":[{"id":"cancer-grand-challenges","kind":"institution","name":"Cancer Grand Challenges","route":"/institutions/cancer-grand-challenges/"},{"id":"cruk","kind":"institution","name":"Cancer Research UK","route":"/institutions/cruk/"},{"id":"columbia-hicc","kind":"institution","name":"Herbert Irving Comprehensive Cancer Center, Columbia University","route":"/institutions/columbia-hicc/"},{"id":"moffitt","kind":"institution","name":"Moffitt Cancer Center","route":"/institutions/moffitt/"},{"id":"oicr","kind":"institution","name":"Ontario Institute for Cancer Research","route":"/institutions/oicr/"},{"id":"francis-crick","kind":"institution","name":"The Francis Crick Institute","route":"/institutions/francis-crick/"}],"term":[{"id":"chromoplexy","kind":"term","name":"Chromoplexy","route":"/terms/chromoplexy/"},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"},{"id":"esr1-mutation","kind":"term","name":"ESR1 mutation","route":"/terms/esr1-mutation/"},{"id":"intra-tumour-heterogeneity","kind":"term","name":"Intra-tumour heterogeneity","route":"/terms/intra-tumour-heterogeneity/"},{"id":"mutational-signature","kind":"term","name":"Mutational signature","route":"/terms/mutational-signature/"},{"id":"neuroendocrine-differentiation","kind":"term","name":"Neuroendocrine differentiation in prostate cancer","route":"/terms/neuroendocrine-differentiation/"},{"id":"oligoprogression","kind":"term","name":"Oligoprogression","route":"/terms/oligoprogression/"},{"id":"vaf","kind":"term","name":"Variant allele frequency (VAF)","route":"/terms/vaf/"}],"trial":[{"id":"circulate-japan","kind":"trial","name":"CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)","route":"/trials/circulate-japan/"},{"id":"serena-6","kind":"trial","name":"SERENA-6","route":"/trials/serena-6/"}],"paper":[{"id":"paper-vogelstein-cancer-genome-landscapes-science-2013","kind":"paper","name":"Cancer genome landscapes: about 140 driver genes, and each tumour needs only a handful","route":"/key-papers/paper-vogelstein-cancer-genome-landscapes-science-2013/"},{"id":"paper-capitello-290-capivasertib-paclitaxel-ann-oncol-2026","kind":"paper","name":"Capivasertib plus paclitaxel as first-line treatment for metastatic triple-negative breast cancer: results from the randomised, global phase III CAPItello-290 trial","route":"/key-papers/paper-capitello-290-capivasertib-paclitaxel-ann-oncol-2026/"},{"id":"paper-mcgranahan-cell","kind":"paper","name":"Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future","route":"/key-papers/paper-mcgranahan-cell/"},{"id":"paper-burstein-tnbc-genomic-subtypes-ccr-2015","kind":"paper","name":"Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer","route":"/key-papers/paper-burstein-tnbc-genomic-subtypes-ccr-2015/"},{"id":"paper-tcga-colorectal-comprehensive-characterization-nature-2012","kind":"paper","name":"Comprehensive molecular characterization of human colon and rectal cancer","route":"/key-papers/paper-tcga-colorectal-comprehensive-characterization-nature-2012/"},{"id":"paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005","kind":"paper","name":"EGFR mutation and resistance of non-small-cell lung cancer to gefitinib","route":"/key-papers/paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005/"},{"id":"paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018","kind":"paper","name":"Genetics and pathogenesis of diffuse large B-cell lymphoma","route":"/key-papers/paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018/"},{"id":"paper-bailey-molecular-subtypes-pancreatic-nature-2016","kind":"paper","name":"Genomic analyses identify molecular subtypes of pancreatic cancer","route":"/key-papers/paper-bailey-molecular-subtypes-pancreatic-nature-2016/"},{"id":"paper-zhang-lung-cancer-never-smokers-nat-genet-2021","kind":"paper","name":"Genomic and evolutionary classification of lung cancer in never smokers","route":"/key-papers/paper-zhang-lung-cancer-never-smokers-nat-genet-2021/"},{"id":"paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011","kind":"paper","name":"Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors","route":"/key-papers/paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011/"},{"id":"paper-gerlinger-intratumour-heterogeneity-nejm-2012","kind":"paper","name":"Gerlinger: a single biopsy misses most of the mutations in a kidney tumour","route":"/key-papers/paper-gerlinger-intratumour-heterogeneity-nejm-2012/"},{"id":"paper-lehmann-tnbc-subtypes-jci-2011","kind":"paper","name":"Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies","route":"/key-papers/paper-lehmann-tnbc-subtypes-jci-2011/"},{"id":"paper-visakorpi-androgen-receptor-amplification-nat-genet-1995","kind":"paper","name":"In vivo amplification of the androgen receptor gene and progression of human prostate cancer","route":"/key-papers/paper-visakorpi-androgen-receptor-amplification-nat-genet-1995/"},{"id":"paper-taylor-integrative-genomic-profiling-cancer-cell-2010","kind":"paper","name":"Integrative genomic profiling of human prostate cancer","route":"/key-papers/paper-taylor-integrative-genomic-profiling-cancer-cell-2010/"},{"id":"paper-chapuy-molecular-subtypes-dlbcl-nat-med-2018","kind":"paper","name":"Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes","route":"/key-papers/paper-chapuy-molecular-subtypes-dlbcl-nat-med-2018/"},{"id":"paper-abbosh-phylogenetic-ctdna-lung-cancer-nature-2017","kind":"paper","name":"Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution","route":"/key-papers/paper-abbosh-phylogenetic-ctdna-lung-cancer-nature-2017/"},{"id":"paper-baca-punctuated-evolution-chromoplexy-cell-2013","kind":"paper","name":"Punctuated evolution of prostate cancer genomes","route":"/key-papers/paper-baca-punctuated-evolution-chromoplexy-cell-2013/"},{"id":"paper-lehmann-tnbctype-4-refinement-plos-one-2016","kind":"paper","name":"Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection","route":"/key-papers/paper-lehmann-tnbctype-4-refinement-plos-one-2016/"},{"id":"paper-mu-sox2-lineage-plasticity-science-2017","kind":"paper","name":"SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer","route":"/key-papers/paper-mu-sox2-lineage-plasticity-science-2017/"},{"id":"paper-tcga-pancancer-atlas-cell-2018","kind":"paper","name":"TCGA Pan-Cancer Atlas: 10,000 tumours across 33 cancer types, classified by molecular features","route":"/key-papers/paper-tcga-pancancer-atlas-cell-2018/"},{"id":"paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","kind":"paper","name":"TCGA: the molecular taxonomy of primary prostate cancer","route":"/key-papers/paper-tcga-molecular-taxonomy-primary-prostate-cell-2015/"},{"id":"paper-gundem-evolutionary-history-lethal-metastatic-prostate-nature-2015","kind":"paper","name":"The evolutionary history of lethal metastatic prostate cancer","route":"/key-papers/paper-gundem-evolutionary-history-lethal-metastatic-prostate-nature-2015/"},{"id":"paper-grasso-mutational-landscape-lethal-crpc-nature-2012","kind":"paper","name":"The mutational landscape of lethal castration-resistant prostate cancer","route":"/key-papers/paper-grasso-mutational-landscape-lethal-crpc-nature-2012/"},{"id":"paper-rosenwald-molecular-profiling-dlbcl-nejm-2002","kind":"paper","name":"The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma","route":"/key-papers/paper-rosenwald-molecular-profiling-dlbcl-nejm-2002/"},{"id":"paper-tracerx-evolution-nature-2023","kind":"paper","name":"TRACERx 421: the full-cohort picture of how lung cancer evolves and which subclones drive relapse","route":"/key-papers/paper-tracerx-evolution-nature-2023/"},{"id":"paper-tracerx-100-nejm-2017","kind":"paper","name":"TRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse","route":"/key-papers/paper-tracerx-100-nejm-2017/"},{"id":"paper-moffitt-virtual-microdissection-subtypes-nat-genet-2015","kind":"paper","name":"Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma","route":"/key-papers/paper-moffitt-virtual-microdissection-subtypes-nat-genet-2015/"}],"roadmap":[{"id":"diagnostics-roadmap","kind":"roadmap","name":"Diagnostics roadmap: stains → gene panels → blood tests that decide treatment","route":"/roadmaps/diagnostics-roadmap/"},{"id":"epigenetics-roadmap","kind":"roadmap","name":"Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome","route":"/roadmaps/epigenetics-roadmap/"},{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch","route":"/roadmaps/lung-cancer-evidence-roadmap/"},{"id":"lymphoma-roadmap","kind":"roadmap","name":"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","route":"/roadmaps/lymphoma-roadmap/"},{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"},{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"},{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"}],"pathway":[{"id":"resistance-routes-map","kind":"pathway","name":"Resistance routes: how a blocked pathway comes back","route":"/pathways/resistance-routes-map/"}]}}