# Acquired resistance to every therapy

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

## TL;DR

Nearly every targeted therapy stops working within months to a few years as the tumour adapts.

## Summary

Every class of anticancer drug is followed by a catalogue of resistance mechanisms: on-target mutations (EGFR C797S, ESR1, BTK C481S, androgen receptor variants), bypass signalling (MET amplification, PI3K activation), lineage plasticity (adenocarcinoma to small-cell or neuroendocrine transformation), drug efflux, antigen loss after CAR-T or ADC therapy, and payload-specific resistance to topoisomerase inhibitors. Even the best first-line targeted therapies in lung cancer produce median progression-free survival of under two years. Because resistance biopsies are rare and mechanisms are heterogeneous between lesions, the choice of next-line therapy is often guesswork, and combination or sequencing strategies designed to pre-empt resistance are seldom tested prospectively. Degraders that remove the target, dual-payload conjugates, ctDNA-triggered switching, and upfront combinations are the emerging countermeasures.

## Fields

- Kind: Bottleneck
- Last checked: 2026-09-08
- Stage: biology
- Severity: critical
- Metrics: Median progression-free survival with first-line osimertinib in EGFR-mutant NSCLC (FLAURA), the benchmark single-agent targeted therapy: 18.9 months (Soria et al., NEJM 2018); Median progression-free survival with sotorasib vs docetaxel in previously treated KRAS G12C NSCLC (CodeBreaK 200): 5.6 vs 4.5 months (de Langen et al., Lancet 2023)
- Causes: Tumours are heterogeneous, so a resistant subclone almost always pre-exists the drug.; Single-agent targeting of one node leaves parallel pathways available for bypass.; Resistance biopsies are uncommon outside academic centres, so mechanisms are inferred rather than measured.; Sequential single-agent development is commercially simpler than testing rational upfront combinations.; Lineage plasticity and epigenetic state changes are not captured by DNA sequencing and have few druggable handles.

## Sources

- Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018): https://doi.org/10.1056/NEJMoa1713137
- Vasan, Baselga & Hyman, A view on drug resistance in cancer (Nature 2019): https://doi.org/10.1038/s41586-019-1730-1

## Connected records

- ideas: [A clone report from blood at every treatment cycle](https://onco.cc/ideas/idea-bio1-ctdna-clone-report/), [A fast route to the matched drug when it is licensed for another cancer](https://onco.cc/ideas/idea-bio1-mechanism-matched-access/), [A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer](https://onco.cc/ideas/idea-tnbc-adc-sequencing-trial/), [A standing platform trial that assigns treatment by how the tumour escaped](https://onco.cc/ideas/idea-bio1-resistance-platform-trial/), [A synthetic lethality map for every cancer driver in every tissue context](https://onco.cc/ideas/idea-moon-synthetic-lethality-map-every-driver/), [Add a drug when the blood test turns, without stopping the one that works](https://onco.cc/ideas/idea-bio1-molecular-progression-add-on/), [Add the second drug on day one when the escape route is predictable](https://onco.cc/ideas/idea-bio1-upfront-bypass-combination/), [An open atlas of collateral sensitivity for every approved targeted drug](https://onco.cc/ideas/idea-bio1-collateral-sensitivity-atlas/), [Autonomous closed-loop adaptive therapy driven by blood tests and evolutionary models](https://onco.cc/ideas/idea-moon-closed-loop-adaptive-therapy/), [Biopsy the one lesion that is growing while the others shrink](https://onco.cc/ideas/idea-bio1-outlier-lesion-biopsy/), [Block the chemical switch that lets cells hide from treatment](https://onco.cc/ideas/idea-bio1-epigenetic-persister-blockade/), [Block the survival signals the tumour's neighbours provide](https://onco.cc/ideas/idea-bio1-stromal-resistance-blockade/), [BTK degraders to pre-empt resistance in frontline CLL](https://onco.cc/ideas/idea-btk-degrader-frontline/), [Check whether a tumour can still show itself to the immune system](https://onco.cc/ideas/idea-bio2-antigen-presentation-triage/), [Clear the zombie cells left behind by chemotherapy and radiotherapy](https://onco.cc/ideas/idea-bio1-senolytics-after-therapy/), [Combination baskets defined by resistance mechanism rather than by cancer type](https://onco.cc/ideas/idea-tr2-resistance-mechanism-baskets/), [ctDNA-guided dose holidays for lung cancer targeted therapy](https://onco.cc/ideas/idea-bio1-ctdna-adaptive-tki/), [Cut off the emergency programme cancer cells use to survive treatment](https://onco.cc/ideas/idea-bio1-stress-response-blockade/), [Design drug pairs where resisting one makes you vulnerable to the other](https://onco.cc/ideas/idea-bio1-evolutionary-double-bind/), [Destroy the truncated androgen receptor that hormone drugs cannot touch](https://onco.cc/ideas/idea-bio1-arv7-degrader/), [Detect tumours changing cell type from RNA in the blood](https://onco.cc/ideas/idea-bio1-cfrna-plasticity-tracking/), [Dual-payload ADCs in first line to prevent resistance](https://onco.cc/ideas/idea-dual-payload-first/), [Every resistance mechanism found in a patient must be rebuilt in the laboratory](https://onco.cc/ideas/idea-bio1-reverse-translation-resistance-models/), [Evolution-guided 'adaptive therapy' dosing tested in randomised phase 2 trials](https://onco.cc/ideas/idea-tr1-adaptive-therapy-randomised-phase-2/), [Find the parts of a tumour the drug never reaches](https://onco.cc/ideas/idea-bio1-drug-exposure-sanctuary-mapping/), [Forecast the next resistance mutation like the weather](https://onco.cc/ideas/idea-bio1-evolution-forecasting/), [Fund a biopsy at progression, every time, as standard care](https://onco.cc/ideas/idea-bio1-mandatory-progression-biopsy/), [Grow models from tumour cells in the blood when a biopsy is impossible](https://onco.cc/ideas/idea-bio1-ctc-derived-explants/), [Kill the sleeping survivor cells with iron-dependent cell death](https://onco.cc/ideas/idea-bio1-persister-ferroptosis/), [Look for the resistant sub-population before the first dose](https://onco.cc/ideas/idea-bio1-baseline-ultradeep-resistant-clones/), [Make post-progression sampling a condition of accelerated approval](https://onco.cc/ideas/idea-bio1-approval-linked-progression-sampling/), [Make resistance a diagnosis: sequence at every progression and choose the next line from what the tumour became](https://onco.cc/ideas/idea-lung-resistance-directed-sequencing-at-every-progression/), [Molecular-progression switching beyond ESR1](https://onco.cc/ideas/idea-ctdna-switch-generalised/), [One open atlas of how tumours escape every drug](https://onco.cc/ideas/idea-bio1-open-resistance-atlas/), [Pause a failed drug so the tumour becomes sensitive to it again](https://onco.cc/ideas/idea-bio1-drug-holiday-resensitisation/), [Payload-class switching as the rule for ADC sequencing](https://onco.cc/ideas/idea-payload-switching/), [Plan the second CAR-T target before the first one is lost](https://onco.cc/ideas/idea-bio1-adaptive-car-antigen-switch/), [Randomise the next line of treatment before the first one fails](https://onco.cc/ideas/idea-bio1-pre-randomised-sequencing-trials/), [Randomise the order of treatment, not only the drugs: a strategy platform for metastatic prostate cancer](https://onco.cc/ideas/idea-prostate-randomise-the-sequence-not-only-the-drugs/), [RAS inhibitor combinations and sequence: pan-RAS plus G12D-selective, plus chemotherapy, and what to give after progression](https://onco.cc/ideas/idea-pdac-ras-inhibitor-combinations-and-sequencing/), [Re-map the tumour's surface proteins before choosing the next antibody drug](https://onco.cc/ideas/idea-bio1-antigen-mapping-at-progression/), [Re-test the metastasis, not the old primary, before every change of treatment](https://onco.cc/ideas/idea-bio1-rebiopsy-before-switch/), [Rotate between drugs on a fixed schedule instead of waiting for failure](https://onco.cc/ideas/idea-bio1-alternating-schedules/), [Sequential multiple-assignment randomised trials to find the best order of ADCs](https://onco.cc/ideas/idea-tr2-smart-sequencing-adc/), [Slow the tumour's mutation engine with APOBEC inhibitors during targeted therapy](https://onco.cc/ideas/idea-bio1-apobec-inhibitor-adjunct/), [SMART designs to test treatment strategies, not just single drugs](https://onco.cc/ideas/idea-tr1-smart-designs-for-adaptive-strategies/), [Starve the survivors: target the energy pathway drug-tolerant cells switch to](https://onco.cc/ideas/idea-bio1-persister-metabolic-vulnerability/), [Switch drugs at maximum response, not at relapse](https://onco.cc/ideas/idea-bio1-first-strike-second-strike/), [Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint](https://onco.cc/ideas/idea-prostate-bipolar-androgen-therapy-phase-3-on-pfs2/), [Test alternating drug schedules against giving both drugs at once](https://onco.cc/ideas/idea-tr2-alternating-vs-concurrent/), [Test intermittent dosing of targeted drugs to delay resistance, with honest priors](https://onco.cc/ideas/idea-tr1-intermittent-dosing-to-delay-resistance/), [Time immunotherapy to the moment targeted drugs make tumours visible](https://onco.cc/ideas/idea-bio1-immunopeptidome-timing/), [Treat resistance like an infectious disease and run national surveillance](https://onco.cc/ideas/idea-bio1-real-world-resistance-surveillance/), [Turn off the error-prone repair that manufactures resistance mutations](https://onco.cc/ideas/idea-bio1-mutagenesis-blockade-rev1/), [Two-target antibody drugs to close the antigen escape route](https://onco.cc/ideas/idea-bio1-dual-antigen-adc-escape/), [Use SLFN11 status to decide which antibody-drug payload to give next](https://onco.cc/ideas/idea-bio1-slfn11-payload-guidance/), [Vaccinate against the resistance mutation before it takes over](https://onco.cc/ideas/idea-bio1-resistance-mutation-vaccine/), [Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it](https://onco.cc/ideas/idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine/), [WRN inhibitors: a second synthetic-lethal win for mismatch-repair cancers](https://onco.cc/ideas/idea-bio1-wrn-msi-programme/)
- collections: [AACR Project GENIE](https://onco.cc/collections/genie/)
- cancers: [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Melanoma](https://onco.cc/cancers/melanoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [ADC payload neutralisers](https://onco.cc/technologies/adc-payload-neutralizer/), [Bispecific ADC](https://onco.cc/technologies/bispecific-adc/), [Dual-payload ADC](https://onco.cc/technologies/dual-payload-adc/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [PROTACs & molecular glues (targeted protein degradation)](https://onco.cc/technologies/protac-degrader/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- drugs: [Amivantamab](https://onco.cc/drugs/amivantamab/), [BGB-16673](https://onco.cc/drugs/bgb-16673/), [Camizestrant](https://onco.cc/drugs/camizestrant/), [Osimertinib](https://onco.cc/drugs/osimertinib/), [Pirtobrutinib](https://onco.cc/drugs/pirtobrutinib/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/), [BeOne Medicines (formerly BeiGene)](https://onco.cc/companies/beone/), [Mersana Therapeutics](https://onco.cc/companies/mersana/), [Nurix Therapeutics](https://onco.cc/companies/nurix/), [Sutro Biopharma](https://onco.cc/companies/sutro-biopharma/), [SystImmune / Sichuan Biokin](https://onco.cc/companies/systimmune/)
- institutions: [Advanced Research Projects Agency for Health](https://onco.cc/institutions/arpa-h/), [Istituto di Candiolo IRCCS (FPO)](https://onco.cc/institutions/candiolo/), [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/), [Moffitt Cancer Center](https://onco.cc/institutions/moffitt/), [The Mark Foundation for Cancer Research](https://onco.cc/institutions/mark-foundation/)
- terms: [ADC sequencing](https://onco.cc/terms/adc-sequencing/), [BCG-unresponsive](https://onco.cc/terms/bcg-unresponsive/), [Bipolar androgen therapy (BAT)](https://onco.cc/terms/bipolar-androgen-therapy/), [Castration-resistant prostate cancer (CRPC)](https://onco.cc/terms/castration-resistance/), [Drug efflux pumps (ABC transporters)](https://onco.cc/terms/efflux-pump/), [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/), [EGFR C797S](https://onco.cc/terms/c797s/), [Endocrine resistance](https://onco.cc/terms/endocrine-resistance/), [ESR1 mutation](https://onco.cc/terms/esr1-mutation/), [Genome-wide loss of heterozygosity (gLOH)](https://onco.cc/terms/genome-wide-loss-of-heterozygosity/), [Histologic transformation](https://onco.cc/terms/histologic-transformation/), [MET amplification (bypass resistance)](https://onco.cc/terms/met-amplification/), [Neuroendocrine differentiation in prostate cancer](https://onco.cc/terms/neuroendocrine-differentiation/), [Radiographic progression-free survival (rPFS)](https://onco.cc/terms/radiographic-progression-free-survival/)
- trials: [BRUIN CLL-321](https://onco.cc/trials/bruin-cll-321/), [CaDAnCe-304](https://onco.cc/trials/cadance-304/), [FLAURA2](https://onco.cc/trials/flaura2/), [MARIPOSA](https://onco.cc/trials/mariposa/), [SERENA-6](https://onco.cc/trials/serena-6/)
- key papers: [A view on drug resistance in cancer](https://onco.cc/key-papers/paper-vasan-nature/), [Abiraterone in metastatic prostate cancer without previous chemotherapy](https://onco.cc/key-papers/paper-abiraterone-acetate-prostate-n-engl-j-med-2013/), [ADMIRAL: gilteritinib pills versus chemotherapy for relapsed FLT3-mutated acute myeloid leukaemia](https://onco.cc/key-papers/paper-admiral-gilteritinib-flt3-nejm-2019/), [AFFIRM: increased survival with enzalutamide in prostate cancer after chemotherapy](https://onco.cc/key-papers/paper-scher-affirm-enzalutamide-nejm-2012/), [Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer](https://onco.cc/key-papers/paper-peters-alex-alectinib-crizotinib-nejm-2017/), [AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer](https://onco.cc/key-papers/paper-antonarakis-ar-v7-resistance-nejm-2014/), [ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer](https://onco.cc/key-papers/paper-ascent-nejm-2021/), [AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation](https://onco.cc/key-papers/paper-augment-101-revumenib-menin-nature-2023/), [BREAKWATER: encorafenib plus cetuximab with chemotherapy as first treatment for BRAF V600E-mutated colorectal cancer](https://onco.cc/key-papers/paper-breakwater-nejm-2025/), [CodeBreaK 200: sotorasib versus docetaxel in KRAS G12C-mutated lung cancer, a modest win for the first KRAS drug](https://onco.cc/key-papers/paper-codebreak-200-lancet-2023/), [CodeBreaK 300: sotorasib plus panitumumab in chemotherapy-refractory KRAS G12C colorectal cancer](https://onco.cc/key-papers/paper-codebreak-300-nejm-2023/), [Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy](https://onco.cc/key-papers/paper-holderfield-ras-on-multi-selective-inhibitor-nature-2024/), [DESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer](https://onco.cc/key-papers/paper-destiny-breast03-nejm-2022/), [EGFR mutation and resistance of non-small-cell lung cancer to gefitinib](https://onco.cc/key-papers/paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005/), [Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC)](https://onco.cc/key-papers/paper-kopetz-beacon-encorafenib-braf-colorectal-nejm-2019/), [EPCORE NHL-1: epcoritamab, a subcutaneous CD20 x CD3 bispecific, in relapsed large B-cell lymphoma including after CAR-T](https://onco.cc/key-papers/paper-epcore-nhl-1-epcoritamab-jco-2023/), [First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer](https://onco.cc/key-papers/paper-shaw-crown-lorlatinib-crizotinib-nejm-2020/), [FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer](https://onco.cc/key-papers/paper-flaura-nejm-2018/), [Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors](https://onco.cc/key-papers/paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011/), [Gerlinger: a single biopsy misses most of the mutations in a kidney tumour](https://onco.cc/key-papers/paper-gerlinger-intratumour-heterogeneity-nejm-2012/), [Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells](https://onco.cc/key-papers/paper-hallmarks-new-dimensions-cancer-discov-2022/), [Huggins and Hodges 1941: the effect of castration, of oestrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate](https://onco.cc/key-papers/paper-huggins-hodges-castration-serum-phosphatases-prostate-1941/), [In vivo amplification of the androgen receptor gene and progression of human prostate cancer](https://onco.cc/key-papers/paper-visakorpi-androgen-receptor-amplification-nat-genet-1995/), [MARIPOSA: amivantamab plus lazertinib versus osimertinib as first treatment for EGFR-mutated lung cancer](https://onco.cc/key-papers/paper-mariposa-nejm-2024/), [Molecular determinants of resistance to antiandrogen therapy](https://onco.cc/key-papers/paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004/), [MURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLL](https://onco.cc/key-papers/paper-murano-venetoclax-rituximab-nejm-2018/), [Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC](https://onco.cc/key-papers/paper-lu-laura-osimertinib-stage-iii-nejm-2024/), [Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC](https://onco.cc/key-papers/paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023/), [Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable](https://onco.cc/key-papers/paper-ostrem-kras-g12c-nature-2013/), [Phase 1 trial of abiraterone acetate confirms that castration-resistant prostate cancer commonly remains hormone driven](https://onco.cc/key-papers/paper-attard-abiraterone-phase-1-cyp17-jco-2008/), [PREVAIL: enzalutamide in metastatic prostate cancer before chemotherapy](https://onco.cc/key-papers/paper-beer-prevail-enzalutamide-nejm-2014/), [QuANTUM-First: quizartinib added to intensive chemotherapy and continued as maintenance in newly diagnosed FLT3-ITD AML](https://onco.cc/key-papers/paper-quantum-first-quizartinib-lancet-2023/), [Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT)](https://onco.cc/key-papers/paper-grothey-correct-regorafenib-lancet-2013/), [RESTORE: bipolar androgen therapy after progression on enzalutamide in metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-teply-restore-bipolar-androgen-therapy-lancet-oncol-2018/), [SOLO-1: two years of olaparib maintenance after first-line chemotherapy for BRCA-mutated ovarian cancer](https://onco.cc/key-papers/paper-solo-1-nejm-2018/), [SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer](https://onco.cc/key-papers/paper-mu-sox2-lineage-plasticity-science-2017/), [SWOG 9916: docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer](https://onco.cc/key-papers/paper-petrylak-swog-9916-docetaxel-estramustine-nejm-2004/), [Tafasitamab, lenalidomide, and rituximab in relapsed or refractory follicular lymphoma (inMIND): a global, phase 3, randomised controlled trial](https://onco.cc/key-papers/paper-inmind-tafasitamab-lenalidomide-rituximab-follicular-lancet-2026/), [TAX 327: docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer](https://onco.cc/key-papers/paper-tannock-tax-327-docetaxel-prednisone-nejm-2004/), [The evolutionary history of lethal metastatic prostate cancer](https://onco.cc/key-papers/paper-gundem-evolutionary-history-lethal-metastatic-prostate-nature-2015/), [The first PROTAC: a chimeric molecule that tags a protein for destruction](https://onco.cc/key-papers/paper-protac-concept-sakamoto-pnas-2001/), [TOPARP-A: DNA-repair defects and olaparib in metastatic prostate cancer](https://onco.cc/key-papers/paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015/), [TRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse](https://onco.cc/key-papers/paper-tracerx-100-nejm-2017/), [TRANSFORMER: bipolar androgen therapy versus enzalutamide in asymptomatic metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021/), [TRITON3: rucaparib or physician's choice in metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-fizazi-triton3-rucaparib-nejm-2023/), [TROPIC: prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel](https://onco.cc/key-papers/paper-de-bono-tropic-cabazitaxel-lancet-2010/), [UCART19: the first gene-edited, donor-derived CAR-T cells in children and adults with relapsed B-cell ALL](https://onco.cc/key-papers/paper-ucart19-allogeneic-car-t-lancet-2020/), [VIALE-A: venetoclax plus azacitidine for older adults with acute myeloid leukaemia who cannot have intensive chemotherapy](https://onco.cc/key-papers/paper-viale-a-venetoclax-azacitidine-nejm-2020/), [ZUMA-2: brexu-cel CAR-T for mantle cell lymphoma that has failed BTK inhibitors](https://onco.cc/key-papers/paper-zuma-2-brexu-cel-mantle-cell-nejm-2020/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/), [Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome](https://onco.cc/roadmaps/epigenetics-roadmap/), [Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test](https://onco.cc/roadmaps/hormonal-therapy-roadmap/), [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](https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/), [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/), [Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch](https://onco.cc/roadmaps/prostate-roadmap/), [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/), [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- pathways: [Drug efflux pumps (ABC transporters)](https://onco.cc/pathways/drug-efflux-pumps/), [Drug-tolerant persister cells](https://onco.cc/pathways/drug-tolerant-persisters/), [Lineage plasticity & neuroendocrine transformation](https://onco.cc/pathways/lineage-plasticity-neuroendocrine/), [Resistance routes: how a blocked pathway comes back](https://onco.cc/pathways/resistance-routes-map/)

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