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The pathway diagrams light up per product; this table asks the inverse question. Across 109 pathways and 972 nodes, 301 nodes name a target in the corpus, 299 of those have at least one product and 2 have none. Pathways are sorted by how many druggable nodes still have no drug, which is where the design opportunities are.
To make a good antibody, a B cell has to deliberately damage its own DNA and keep dividing while it does. The germinal centre is where that happens, under strict time limits. Most B-cell lymphomas are cells that went through it and did not come out.
Treatments hitting this pathway, as a filterable tablePathway page and diagram
How drugs attack it, from the pathway page: EZH2 inhibition (tazemetostat) in follicular lymphoma, which is the only licensed drug that acts on this reaction directly and the only one selected by a germinal-centre genotype; BCL-2 inhibition (venetoclax) against the anti-apoptotic protein the t(14;18) translocation put there; HDAC inhibition as the proposed answer to CREBBP loss, on the argument that a cell short of acetyltransferase is dependent on keeping the deacetylase in check; in trials, not approved for this indication; BCL6 degraders and inhibitors, in early trials; Every anti-CD19, anti-CD20, anti-CD79b and anti-CD22 medicine, which work because the lymphoma kept the surface of the normal cell it came from.
KEGG's non-small cell lung cancer map shows a set of alternative on-switches (EGFR mutation, KRAS mutation, EML4-ALK, RET and MET alterations) that all feed the same RAS/ERK, PI3K/AKT and STAT relays, plus loss of the p16 and p53 brakes. Each on-switch now has its own targeted pill, which is why molecular testing comes before treatment.
Treatments hitting this pathway, as a filterable tablePathway page and diagram
How drugs attack it, from the pathway page: EGFR-mutant disease: osimertinib (alone or with chemotherapy), amivantamab plus lazertinib; amivantamab or sunvozertinib for exon 20 insertions; KRAS G12C: sotorasib, adagrasib, divarasib, olomorasib; ALK fusions: alectinib, brigatinib, lorlatinib; RET fusions: selpercatinib, pralsetinib; MET exon 14 or overexpression: savolitinib, telisotuzumab vedotin; BRAF V600E: dabrafenib plus trametinib; HER2 mutations: trastuzumab deruxtecan, zongertinib; Driver-negative tumours: pembrolizumab or other PD-1/PD-L1 antibodies with or without platinum chemotherapy.
KEGG's breast cancer map lays out the three clinical subtypes as signalling routes: oestrogen receptor driving cyclin D and CDK4/6 in hormone-receptor-positive disease, HER2 driving PI3K/AKT and MAPK in HER2-positive disease, and EGFR, Notch, Wnt and BRCA defects in triple-negative disease. Each route has its own drug class.
Treatments hitting this pathway, as a filterable tablePathway page and diagram
How drugs attack it, from the pathway page: HR-positive disease: endocrine therapy (letrozole, tamoxifen, fulvestrant, oral SERDs elacestrant, imlunestrant, camizestrant) with a CDK4/6 inhibitor (palbociclib, ribociclib, abemaciclib), then alpelisib, inavolisib or capivasertib for PIK3CA, AKT1 or PTEN alterations; HER2-positive disease: trastuzumab plus pertuzumab, trastuzumab emtansine, trastuzumab deruxtecan, and the HER2 kinase inhibitors tucatinib, neratinib and lapatinib; Triple-negative disease: pembrolizumab with chemotherapy, TROP2 antibody-drug conjugates sacituzumab govitecan and datopotamab deruxtecan; PARP inhibitors olaparib and talazoparib for germline BRCA1/2-mutated breast cancer; Trastuzumab deruxtecan for HER2-low tumours across subtypes.
This KEGG map shows the order of genetic hits that turn normal pancreatic duct cells into ductal adenocarcinoma: KRAS mutation first, then loss of the p16 brake, then loss of TP53, SMAD4 and BRCA2. It matters because nearly every pancreatic cancer is driven by KRAS, which until recently had no drug.
Treatments hitting this pathway, as a filterable tablePathway page and diagram
How drugs attack it, from the pathway page: Direct KRAS inhibition: sotorasib or adagrasib for KRAS G12C; pan-RAS(ON) inhibitor daraxonrasib in phase 3 for G12D/G12V disease; PARP inhibitor olaparib as maintenance for germline BRCA-mutant tumours after platinum chemotherapy; EGFR inhibitor erlotinib with gemcitabine (small benefit, listed by KEGG); NTRK fusion tumours: larotrectinib, entrectinib; MSI-high tumours: pembrolizumab; Chemotherapy backbone: FOLFIRINOX or gemcitabine with nab-paclitaxel.
This KEGG map shows the two genetic roads to glioblastoma: primary tumours amplify EGFR and lose PTEN and p16, secondary tumours from lower-grade astrocytomas over-express PDGF and CDK4 and lose TP53 and RB. It explains why growth-factor and cell-cycle drugs are the main targeted options in brain tumours, and why paediatric low-grade gliomas with BRAF changes respond to MAPK inhibitors.
Treatments hitting this pathway, as a filterable tablePathway page and diagram
How drugs attack it, from the pathway page: Paediatric low-grade glioma: BRAF-MAPK inhibitors tovorafenib (listed by KEGG), dabrafenib plus trametinib for BRAF V600E, selumetinib or mirdametinib for NF1-related tumours; IDH-mutant grade 2 glioma: vorasidenib; Glioblastoma: temozolomide with radiotherapy (MGMT methylated tumours benefit most), bevacizumab for symptom control; EGFR and PDGFR inhibitors and CDK4/6 inhibitors have not yet shown benefit in glioblastoma trials.
Two genes are synthetically lethal when losing either alone is fine but losing both kills the cell. Cancers that have already lost one (a tumour suppressor you cannot put back) become uniquely dependent on the other, which you can drug. BRCA and PARP was the first proof; a dozen more pairs are now in trials.
Treatments hitting this pathway, as a filterable tablePathway page and diagram
How drugs attack it, from the pathway page: PARP inhibitors for BRCA/HRD (approved in four cancers); MTA-cooperative PRMT5 inhibitors for MTAP-deleted tumours (mesothelioma, NSCLC, pancreatic; phase 1-2); WEE1 (azenosertib), PKMYT1 (lunresertib) and ATR (ceralasertib, camonsertib) inhibitors in TP53-mutant, CCNE1-amplified and ATM-deficient tumours; WRN inhibitors for MSI-H; SMARCA2 degraders for SMARCA4-deficient cancers.
KEGG's AML map shows the two hits that turn a normal blood stem cell into a leukaemia: a growth signal jammed on (FLT3, KIT or RAS) plus a broken maturation switch (fusion proteins such as PML-RARA or AML1-ETO, or mutated CEBPA and RUNX1). Drugs now exist for both halves.
Treatments hitting this pathway, as a filterable tablePathway page and diagram
How drugs attack it, from the pathway page: FLT3 inhibitors: midostaurin with induction chemotherapy, gilteritinib for relapsed or refractory FLT3-mutant AML, quizartinib for FLT3-ITD AML; Differentiation therapy for PML-RARA acute promyelocytic leukaemia: all-trans retinoic acid plus arsenic trioxide; BCL2 inhibitor venetoclax with azacitidine for patients unfit for intensive chemotherapy; Menin inhibitors (revumenib) for NPM1-mutant and KMT2A-rearranged AML, which reopen the differentiation programme; Intensive chemotherapy (cytarabine and daunorubicin) followed by allogeneic stem cell transplant in fit, higher-risk patients.
Tumours come in three immune weathers: inflamed (T cells inside, checkpoint drugs work), excluded (T cells stuck at the edge), and desert (no T cells at all). Most common cancers are excluded or desert, and turning them 'hot' is the central problem of immunotherapy.
Treatments hitting this pathway, as a filterable tablePathway page and diagram
How drugs attack it, from the pathway page: Radiotherapy, immunogenic chemotherapy and TOP1 ADCs to seed antigen and STING signalling; oncolytic viruses (T-VEC, RP1) and in situ vaccination; Anti-VEGF and PD-1×VEGF bispecifics open the vessel gate; FAP-, CXCR4- and TGF-β-directed agents (mostly modest so far); Epigenetic priming (EZH2, DNMT inhibitors) to restore chemokines; STING agonists intratumourally; Bypass the weather: T-cell engagers, CAR-T, TCR-T and vaccines that bring or make their own T cells.
This KEGG map splits stomach cancer into two routes: the intestinal type that accumulates TP53, APC and HER2 changes step by step, and the diffuse type driven by loss of the cell glue E-cadherin plus MET or FGFR2 amplification. It matters because HER2, FGFR2, claudin 18.2 and PD-1 status now decide first-line treatment.
Treatments hitting this pathway, as a filterable tablePathway page and diagram
How drugs attack it, from the pathway page: HER2-positive: trastuzumab plus chemotherapy and pembrolizumab first line; trastuzumab deruxtecan or zanidatamab after progression; HER2-negative, PD-L1 expressing: nivolumab or pembrolizumab with chemotherapy; Claudin 18.2-positive: zolbetuximab with chemotherapy; FGFR2b over-expressing: bemarituzumab (phase 3); MET amplified: MET inhibitors in trials; Second line: ramucirumab (VEGFR2) with paclitaxel; MSI-high: checkpoint inhibitors; E-cadherin/CDH1 loss: no direct drug yet.
This KEGG map shows how hepatitis viruses, alcohol and aflatoxin leave the liver with mutations in telomerase, TP53, Wnt/beta-catenin, PI3K/AKT/mTOR and the oxidative stress sensor NRF2, which together drive liver cancer. It matters because the map explains why liver cancer is treated mainly with angiogenesis blockers and immunotherapy rather than a single targeted drug.
Treatments hitting this pathway, as a filterable tablePathway page and diagram
How drugs attack it, from the pathway page: First line: atezolizumab plus bevacizumab (PD-L1 plus VEGF) or durvalumab plus tremelimumab (PD-L1 plus CTLA-4); Multikinase inhibitors sorafenib and lenvatinib (listed by KEGG), and camrelizumab plus rivoceranib or donafenib in China; Second line: regorafenib, cabozantinib (also blocks MET), ramucirumab for AFP-high disease; Glypican-3 directed antibodies and CAR-T cells in clinical trials; Wnt/beta-catenin and TERT steps: no approved drug yet.
A node counts as drugged when a product in the corpus lists its target; a druggable node with no drug means no product in OnCo names that target, not that none exists anywhere. Nodes without a target id are pathway components (ligands, complexes, processes) that have no target page yet.