{"entity":{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","aka":[],"tldr":"Targeted drugs switch off the specific broken protein a cancer depends on. The first ones turned a leukaemia into a chronic condition; the field then learned that resistance is the rule, designed drugs around it, and has now reached the drivers that were called impossible to target.","summary":"Tamoxifen (1977) and trastuzumab (1998) were targeted therapies before the term existed, but imatinib (2001) defined the category: a pill against the one enzyme a cancer cannot live without, matched to the patients whose tumours carry it. EGFR, ALK and BRAF followed within a decade, and with them the lesson that shaped everything since: nearly every targeted drug stops working within months to years, and the mechanism of escape can be read from the tumour and drugged in turn.\n\nThe second generation was designed for resistance and the brain: osimertinib, alectinib and lorlatinib, then their use after surgery (ADAURA, ALINA) and after chemoradiation (LAURA). PARP inhibitors made an inherited DNA-repair defect a treatable target; tissue-agnostic approvals made the mutation, not the organ, the indication. The third generation is reaching targets that were called undruggable: KRAS G12C (sotorasib 2021), then G12D and pan-RAS(ON) inhibitors, HIF-2 in kidney cancer, menin in leukaemia, and protein degraders (vepdegestrant, the first approved PROTAC, 2026) that remove a protein rather than block it.\n\nThe pace is set by resistance biology, by the combinatorial space of pairings that trials cannot search, by prices that compound over years of therapy, and by biomarkers that must be validated before a drug can be matched to a patient.","asOf":"2026-09-10","links":[{"label":"Druker et al., imatinib in CML (NEJM 2001)","url":"https://www.nejm.org/doi/full/10.1056/NEJM200104053441401"}],"tags":[],"related":["kras-roadmap","hormonal-therapy-roadmap","epigenetics-roadmap","idea-bio1-ctdna-adaptive-tki","idea-tr2-resistance-mechanism-baskets","idea-bio1-resistance-platform-trial","idea-bio1-evolution-forecasting","idea-bio1-adaptive-therapy-platform","idea-tr1-adaptive-therapy-randomised-phase-2","idea-bio1-resistance-mutation-vaccine","eprenetapopt","myc","mrtx1133","lung-cancer-evidence-roadmap","prostate-roadmap","idea-prostate-hrr-testing-at-metastatic-diagnosis"],"cancers":[],"sections":["targeted-therapy"],"technologies":["kinase-inhibitors","parp-inhibitor","kras-inhibitors","protac-degrader","molecular-glue-platforms","degrader-antibody-conjugate","synthetic-lethality-approaches","antisense-sirna","de-novo-protein-design","companion-diagnostic","liquid-biopsy","cgp"],"targets":["egfr","alk","kras","her2","braf","ret","ntrk","ros1","prmt5-mtap","btk","flt3","brca"],"drugs":["imatinib","trastuzumab","gefitinib","erlotinib","osimertinib","amivantamab","lazertinib","crizotinib","alectinib","lorlatinib","neladalkib","dabrafenib-trametinib","olaparib","larotrectinib","entrectinib","selpercatinib","sotorasib","adagrasib","divarasib","daraxonrasib","zoldonrasib","elironrasib","olomorasib","vepdegestrant","pirtobrutinib","cabozantinib","pemigatinib","eli-002-7p"],"companies":["nuvalent","frontier-medicines","black-diamond-therapeutics"],"institutions":["ohsu-knight"],"pathways":[],"terms":["tumour-agnostic","resistance"],"trials":["hera-b31-n9831","toga","flaura2","mariposa","adaura","alina","laura","alkove-1","combi-ad","dreamseq","solo-1","olympia","profound","libretto-431","codebreak-200","krystal-12","krascendo-1","codebreak-300","rasolute-302","litespark-005","veritac-2","cadance-304","bruin-cll-321","serena-6","insight-gist","telimet-nsclc-01","gefitinib-chemo-tmh"],"people":[],"bottlenecks":["b-resistance","b-undruggable-targets","b-tumor-heterogeneity","b-combination-space","b-drug-pricing","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"steps":[{"era":"1977-2001","title":"The idea of a target","description":"Tamoxifen blocked the oestrogen receptor and trastuzumab (1998) the HER2 protein, each with a test to find the patients whose tumours depended on them. Imatinib (2001) proved the concept in its purest form: a pill against BCR-ABL, the one enzyme chronic myeloid leukaemia cannot live without, that turned a fatal disease into a chronic one and made Brian Druker's Oregon clinic the birthplace of precision oncology.","refs":["tamoxifen","trastuzumab","hera-b31-n9831","toga","imatinib","kinase-inhibitors","ohsu-knight","companion-diagnostic"],"status":"historic"},{"era":"2004-2013","title":"Oncogene addiction, and the resistance lesson","description":"EGFR mutations (2004) explained why gefitinib and erlotinib worked spectacularly in a minority of lung cancers; crizotinib for ALK (2011) and vemurafenib for BRAF (2011) followed within months of the target being found. Then nearly every responder relapsed: T790M in EGFR, gatekeeper mutations in ALK, MAPK reactivation in BRAF. Resistance became the central problem of the field, and reading it from a biopsy became the route to the next drug.","refs":["gefitinib","erlotinib","egfr","crizotinib","alk","braf","dabrafenib-trametinib","resistance","b-resistance","gefitinib-chemo-tmh"],"status":"historic"},{"era":"2014-2020","title":"Designed for resistance, the brain and the adjuvant setting","description":"Osimertinib was built to hit T790M and cross into the brain; alectinib and lorlatinib did the same for ALK. Given after surgery, the pills halved the risk of death in EGFR-mutant lung cancer (ADAURA) and sharply cut recurrence in ALK-positive disease (ALINA); LAURA extended them to after chemoradiation. Olaparib (2014) made an inherited BRCA defect a target in ovarian, breast and prostate cancer (SOLO-1, OlympiA, PROfound). Larotrectinib's approval for any NTRK-fusion tumour (2018) made the mutation, not the organ, the indication; RET (LIBRETTO-431) and ROS1 followed. COMBI-AD proved a year of BRAF-MEK pills after melanoma surgery halves relapse; DREAMseq settled that immunotherapy should come first.","refs":["osimertinib","alectinib","lorlatinib","adaura","alina","laura","parp-inhibitor","olaparib","solo-1","olympia","profound","brca","larotrectinib","entrectinib","selpercatinib","libretto-431","tumour-agnostic","ntrk","ret","ros1","combi-ad","dreamseq"],"status":"current"},{"era":"2021-2026","title":"The undruggable drivers fall","description":"KRAS, mutated in a quarter of cancers and called undruggable for forty years, yielded to sotorasib (2021) and adagrasib, which lock the G12C mutant in its off state; CodeBreaK 200 and KRYSTAL-12 showed they beat chemotherapy, and divarasib beat both head to head (Krascendo 1). The G12D mutation, the commonest in pancreatic cancer, has its first drug in zoldonrasib, and daraxonrasib inhibits every RAS in its active state (RASolute 302). Elsewhere belzutifan drugged HIF-2, menin inhibitors reached leukaemia, and vepdegestrant (2026) became the first approved PROTAC, removing its target rather than blocking it. MARIPOSA and FLAURA2 showed that combinations beat osimertinib alone.","refs":["kras-inhibitors","kras","sotorasib","adagrasib","codebreak-200","krystal-12","divarasib","krascendo-1","codebreak-300","zoldonrasib","mrtx1133","daraxonrasib","rasolute-302","elironrasib","olomorasib","kras-roadmap","litespark-005","protac-degrader","vepdegestrant","veritac-2","mariposa","amivantamab","lazertinib","flaura2"],"status":"current"},{"era":"2026-2030","title":"Fourth generations, degraders and switching on a blood test","description":"Neladalkib is designed to work after lorlatinib (ALKOVE-1); pirtobrutinib works after other BTK inhibitors and a BTK degrader is in phase 3 (CaDAnCe-304); the first MET-directed ADC is in its confirmatory trial. SERENA-6 changed endocrine therapy on a blood test before the scan changed, and INSIGHT is matching GIST drugs to the resistance mutation found in blood. The next trial designs assign treatment by how the tumour escaped rather than where it started.","refs":["neladalkib","alkove-1","nuvalent","pirtobrutinib","bruin-cll-321","cadance-304","btk","telimet-nsclc-01","serena-6","insight-gist","liquid-biopsy","idea-bio1-ctdna-adaptive-tki","idea-tr2-resistance-mechanism-baskets","idea-bio1-resistance-platform-trial"],"status":"emerging"},{"era":"2026-2032","title":"New modalities for the old targets","description":"Molecular glues and degraders reach proteins without a druggable pocket; degrader-antibody conjugates deliver them into the tumour; antisense and siRNA silence the gene rather than the protein; designed proteins grip surfaces no small molecule can. Synthetic lethality finds a second gene a cancer needs only because its first is broken: PRMT5 inhibitors for MTAP-deleted tumours and WRN inhibitors for mismatch-repair-deficient ones are the leading examples. Chemoproteomics is finding covalent handles on KRAS and beyond.","refs":["molecular-glue-platforms","degrader-antibody-conjugate","antisense-sirna","de-novo-protein-design","synthetic-lethality-approaches","prmt5-mtap","frontier-medicines","black-diamond-therapeutics"],"status":"emerging"},{"era":"2030+","title":"Forecasting resistance instead of waiting for it","description":"If the next resistance mutation can be predicted, as flu strains are, it could be blocked or vaccinated against before it takes over; adaptive dosing that keeps the sensitive clone dominant is in randomised phase 2. MYC and mutant p53, the drivers still without a drug, are the open frontier, and eprenetapopt's failure to refold p53 shows how hard it is. A ready-made KRAS vaccine after pancreatic surgery missed its primary goal, but the idea of vaccinating against a driver mutation remains live.","refs":["idea-bio1-evolution-forecasting","idea-bio1-resistance-mutation-vaccine","idea-bio1-adaptive-therapy-platform","idea-tr1-adaptive-therapy-randomised-phase-2","myc","eprenetapopt","b-undruggable-targets","eli-002-7p"],"status":"speculative"},{"era":"What sets the pace","title":"Resistance, combinations, biomarkers and price","description":"Every targeted drug meets resistance; a tumour is many tumours, so the resistant clone is usually already there. There are thousands of possible combinations and sequences and trials can test a few dozen a year. A drug cannot be matched without a validated test, and tests lag drugs. And targeted therapy is priced per month for years, so the cost of a cure-like outcome compounds; the biosimilar and generic wave for the first generation is only now arriving.","refs":["b-resistance","b-tumor-heterogeneity","b-combination-space","b-biomarker-validation","b-drug-pricing","b-undruggable-targets"],"status":"current"}],"watch":[]},"route":"/roadmaps/targeted-therapy-roadmap/","neighbours":{"roadmap":[{"id":"epigenetics-roadmap","kind":"roadmap","name":"Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome","route":"/roadmaps/epigenetics-roadmap/"},{"id":"hormonal-therapy-roadmap","kind":"roadmap","name":"Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test","route":"/roadmaps/hormonal-therapy-roadmap/"},{"id":"kras-roadmap","kind":"roadmap","name":"KRAS roadmap: undruggable → G12C → pan-RAS","route":"/roadmaps/kras-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":"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":"prostate-roadmap","kind":"roadmap","name":"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","route":"/roadmaps/prostate-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/"}],"idea":[{"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-resistance-platform-trial","kind":"idea","name":"A standing platform trial that assigns treatment by how the tumour escaped","route":"/ideas/idea-bio1-resistance-platform-trial/"},{"id":"idea-tr2-resistance-mechanism-baskets","kind":"idea","name":"Combination baskets defined by resistance mechanism rather than by cancer type","route":"/ideas/idea-tr2-resistance-mechanism-baskets/"},{"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-tr1-adaptive-therapy-randomised-phase-2","kind":"idea","name":"Evolution-guided 'adaptive therapy' dosing tested in randomised phase 2 trials","route":"/ideas/idea-tr1-adaptive-therapy-randomised-phase-2/"},{"id":"idea-bio1-evolution-forecasting","kind":"idea","name":"Forecast the next resistance mutation like the weather","route":"/ideas/idea-bio1-evolution-forecasting/"},{"id":"idea-prostate-hrr-testing-at-metastatic-diagnosis","kind":"idea","name":"Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later","route":"/ideas/idea-prostate-hrr-testing-at-metastatic-diagnosis/"},{"id":"idea-bio1-resistance-mutation-vaccine","kind":"idea","name":"Vaccinate against the resistance mutation before it takes over","route":"/ideas/idea-bio1-resistance-mutation-vaccine/"}],"drug":[{"id":"adagrasib","kind":"drug","name":"Adagrasib","route":"/drugs/adagrasib/"},{"id":"alectinib","kind":"drug","name":"Alectinib","route":"/drugs/alectinib/"},{"id":"amivantamab","kind":"drug","name":"Amivantamab","route":"/drugs/amivantamab/"},{"id":"cabozantinib","kind":"drug","name":"Cabozantinib","route":"/drugs/cabozantinib/"},{"id":"crizotinib","kind":"drug","name":"Crizotinib","route":"/drugs/crizotinib/"},{"id":"dabrafenib-trametinib","kind":"drug","name":"Dabrafenib + trametinib","route":"/drugs/dabrafenib-trametinib/"},{"id":"daraxonrasib","kind":"drug","name":"Daraxonrasib","route":"/drugs/daraxonrasib/"},{"id":"divarasib","kind":"drug","name":"Divarasib","route":"/drugs/divarasib/"},{"id":"eli-002-7p","kind":"drug","name":"ELI-002 7P","route":"/drugs/eli-002-7p/"},{"id":"elironrasib","kind":"drug","name":"Elironrasib","route":"/drugs/elironrasib/"},{"id":"entrectinib","kind":"drug","name":"Entrectinib","route":"/drugs/entrectinib/"},{"id":"eprenetapopt","kind":"drug","name":"Eprenetapopt","route":"/drugs/eprenetapopt/"},{"id":"erlotinib","kind":"drug","name":"Erlotinib","route":"/drugs/erlotinib/"},{"id":"gefitinib","kind":"drug","name":"Gefitinib","route":"/drugs/gefitinib/"},{"id":"imatinib","kind":"drug","name":"Imatinib","route":"/drugs/imatinib/"},{"id":"larotrectinib","kind":"drug","name":"Larotrectinib","route":"/drugs/larotrectinib/"},{"id":"lazertinib","kind":"drug","name":"Lazertinib","route":"/drugs/lazertinib/"},{"id":"lorlatinib","kind":"drug","name":"Lorlatinib","route":"/drugs/lorlatinib/"},{"id":"mrtx1133","kind":"drug","name":"MRTX1133","route":"/drugs/mrtx1133/"},{"id":"neladalkib","kind":"drug","name":"Neladalkib","route":"/drugs/neladalkib/"},{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"},{"id":"olomorasib","kind":"drug","name":"Olomorasib","route":"/drugs/olomorasib/"},{"id":"osimertinib","kind":"drug","name":"Osimertinib","route":"/drugs/osimertinib/"},{"id":"pemigatinib","kind":"drug","name":"Pemigatinib","route":"/drugs/pemigatinib/"},{"id":"pirtobrutinib","kind":"drug","name":"Pirtobrutinib","route":"/drugs/pirtobrutinib/"},{"id":"selpercatinib","kind":"drug","name":"Selpercatinib","route":"/drugs/selpercatinib/"},{"id":"sotorasib","kind":"drug","name":"Sotorasib","route":"/drugs/sotorasib/"},{"id":"tamoxifen","kind":"drug","name":"Tamoxifen","route":"/drugs/tamoxifen/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"vepdegestrant","kind":"drug","name":"Vepdegestrant","route":"/drugs/vepdegestrant/"},{"id":"zoldonrasib","kind":"drug","name":"Zoldonrasib","route":"/drugs/zoldonrasib/"}],"pathway":[{"id":"myc","kind":"pathway","name":"MYC","route":"/pathways/myc/"}],"section":[{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"technology":[{"id":"companion-diagnostic","kind":"technology","name":"Companion diagnostics","route":"/technologies/companion-diagnostic/"},{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"de-novo-protein-design","kind":"technology","name":"De novo designed protein binders","route":"/technologies/de-novo-protein-design/"},{"id":"degrader-antibody-conjugate","kind":"technology","name":"Degrader-antibody conjugate (DAC)","route":"/technologies/degrader-antibody-conjugate/"},{"id":"kras-inhibitors","kind":"technology","name":"KRAS & RAS inhibitors","route":"/technologies/kras-inhibitors/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"molecular-glue-platforms","kind":"technology","name":"Molecular glue discovery platforms","route":"/technologies/molecular-glue-platforms/"},{"id":"antisense-sirna","kind":"technology","name":"Oligonucleotide therapeutics","route":"/technologies/antisense-sirna/"},{"id":"parp-inhibitor","kind":"technology","name":"PARP inhibitors","route":"/technologies/parp-inhibitor/"},{"id":"protac-degrader","kind":"technology","name":"PROTACs & molecular glues (targeted protein degradation)","route":"/technologies/protac-degrader/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"},{"id":"synthetic-lethality-approaches","kind":"technology","name":"Synthetic lethality approaches","route":"/technologies/synthetic-lethality-approaches/"}],"target":[{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/"},{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"btk","kind":"target","name":"BTK (Bruton tyrosine kinase)","route":"/targets/btk/"},{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"flt3","kind":"target","name":"FLT3","route":"/targets/flt3/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"ntrk","kind":"target","name":"NTRK","route":"/targets/ntrk/"},{"id":"prmt5-mtap","kind":"target","name":"PRMT5 (MTAP-deleted cancers)","route":"/targets/prmt5-mtap/"},{"id":"ret","kind":"target","name":"RET","route":"/targets/ret/"},{"id":"ros1","kind":"target","name":"ROS1","route":"/targets/ros1/"}],"company":[{"id":"black-diamond-therapeutics","kind":"company","name":"Black Diamond Therapeutics","route":"/companies/black-diamond-therapeutics/"},{"id":"frontier-medicines","kind":"company","name":"Frontier Medicines","route":"/companies/frontier-medicines/"},{"id":"nuvalent","kind":"company","name":"Nuvalent","route":"/companies/nuvalent/"}],"institution":[{"id":"ohsu-knight","kind":"institution","name":"OHSU Knight Cancer Institute","route":"/institutions/ohsu-knight/"}],"term":[{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"}],"trial":[{"id":"adaura","kind":"trial","name":"ADAURA","route":"/trials/adaura/"},{"id":"alina","kind":"trial","name":"ALINA","route":"/trials/alina/"},{"id":"alkove-1","kind":"trial","name":"ALKOVE-1","route":"/trials/alkove-1/"},{"id":"bruin-cll-321","kind":"trial","name":"BRUIN CLL-321","route":"/trials/bruin-cll-321/"},{"id":"cadance-304","kind":"trial","name":"CaDAnCe-304","route":"/trials/cadance-304/"},{"id":"codebreak-200","kind":"trial","name":"CodeBreaK 200","route":"/trials/codebreak-200/"},{"id":"codebreak-300","kind":"trial","name":"CodeBreaK 300","route":"/trials/codebreak-300/"},{"id":"combi-ad","kind":"trial","name":"COMBI-AD","route":"/trials/combi-ad/"},{"id":"dreamseq","kind":"trial","name":"DREAMseq (ECOG-ACRIN EA6134)","route":"/trials/dreamseq/"},{"id":"flaura2","kind":"trial","name":"FLAURA2","route":"/trials/flaura2/"},{"id":"gefitinib-chemo-tmh","kind":"trial","name":"Gefitinib vs gefitinib plus pemetrexed-carboplatin in EGFR-mutant lung cancer (Tata Memorial)","route":"/trials/gefitinib-chemo-tmh/"},{"id":"hera-b31-n9831","kind":"trial","name":"HERA, NSABP B-31 & NCCTG N9831 (adjuvant trastuzumab)","route":"/trials/hera-b31-n9831/"},{"id":"insight-gist","kind":"trial","name":"INSIGHT","route":"/trials/insight-gist/"},{"id":"krascendo-1","kind":"trial","name":"Krascendo 1","route":"/trials/krascendo-1/"},{"id":"krystal-12","kind":"trial","name":"KRYSTAL-12","route":"/trials/krystal-12/"},{"id":"laura","kind":"trial","name":"LAURA","route":"/trials/laura/"},{"id":"libretto-431","kind":"trial","name":"LIBRETTO-431","route":"/trials/libretto-431/"},{"id":"litespark-005","kind":"trial","name":"LITESPARK-005","route":"/trials/litespark-005/"},{"id":"mariposa","kind":"trial","name":"MARIPOSA","route":"/trials/mariposa/"},{"id":"olympia","kind":"trial","name":"OlympiA","route":"/trials/olympia/"},{"id":"profound","kind":"trial","name":"PROfound","route":"/trials/profound/"},{"id":"rasolute-302","kind":"trial","name":"RASolute 302","route":"/trials/rasolute-302/"},{"id":"serena-6","kind":"trial","name":"SERENA-6","route":"/trials/serena-6/"},{"id":"solo-1","kind":"trial","name":"SOLO-1","route":"/trials/solo-1/"},{"id":"telimet-nsclc-01","kind":"trial","name":"TeliMET NSCLC-01","route":"/trials/telimet-nsclc-01/"},{"id":"toga","kind":"trial","name":"ToGA","route":"/trials/toga/"},{"id":"veritac-2","kind":"trial","name":"VERITAC-2","route":"/trials/veritac-2/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-drug-pricing","kind":"bottleneck","name":"Prices and value","route":"/bottlenecks/b-drug-pricing/"},{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"},{"id":"b-combination-space","kind":"bottleneck","name":"Too many combinations to test","route":"/bottlenecks/b-combination-space/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}],"paper":[{"id":"paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004","kind":"paper","name":"Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib","route":"/key-papers/paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004/"},{"id":"paper-paez-egfr-mutations-gefitinib-science-2004","kind":"paper","name":"EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy","route":"/key-papers/paper-paez-egfr-mutations-gefitinib-science-2004/"},{"id":"paper-soda-eml4-alk-fusion-nature-2007","kind":"paper","name":"Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer","route":"/key-papers/paper-soda-eml4-alk-fusion-nature-2007/"},{"id":"paper-sandler-ecog-4599-bevacizumab-nsclc-nejm-2006","kind":"paper","name":"Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer","route":"/key-papers/paper-sandler-ecog-4599-bevacizumab-nsclc-nejm-2006/"}]}}