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Growth-factor receptors are antennas on the cell surface that pair up when a signal lands and switch on the growth relays inside. Cancers mutate, multiply, or fuse these antennas so they broadcast 'grow' with no signal at all. Most targeted drugs, antibodies and ADCs start here.
Ligand binding (EGF, HGF, FGF, NRG, SCF, PDGF, VEGF) dimerises RTKs, trans-autophosphorylating tyrosines that recruit SH2/PTB adaptors: GRB2-SOS to RAS-MAPK, p85 to PI3K-AKT, PLCγ, SRC, STAT3/5, and CBL for ubiquitin-mediated downregulation. Oncogenic activation: kinase-domain mutations (EGFR L858R/exon 19, exon 20 insertions; FLT3-ITD; KIT exon 11; HER2), extracellular-domain truncation (EGFRvIII), amplification (HER2, MET, FGFR1/2), fusions (ALK, ROS1, RET, NTRK, FGFR2/3, with dimerisation domains that pair the kinase constitutively), autocrine loops, and PTPN11 or CBL loss. Drug classes: reversible and covalent TKIs (with resistance via gatekeeper/solvent-front mutations such as EGFR C797S, ALK G1202R), antibodies that block ligand or receptor and recruit Fc effectors (trastuzumab, cetuximab), bispecifics (amivantamab EGFR×MET, zanidatamab HER2×HER2), and ADCs that use the receptor as a delivery address regardless of signalling (T-DXd on HER2-low). Bypass via a parallel RTK (MET amplification under EGFR blockade, HER3 upregulation) is the classic escape.
Two halves of a walkie-talkie that only transmit when clipped together by a signal from outside. Cancer glues them together (fusions, mutations) or installs hundreds of extra sets (amplification), so the room is full of shouted 'grow' orders. TKIs pull the battery, antibodies tape over the microphone, ADCs use the aerial as a mailing address for poison.
Every KRAS wild-type pancreatic cancer should be tested for NRG1 fusions because a specific, approved antibody now exists; zenocutuzumab is the first targeted drug approved for a pancreatic cancer driver.
This is the paper Europe PMC returns for registry id NCT04744831 with the most citations, so it is the natural first reading for anyone following the DESTINY-CRC02 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
The first United States approval of a HER2-directed regimen in colorectal cancer, and the basis for MOUNTAINEER-03, which is testing the combination with chemotherapy in the first line.
This is the fusion and immune-marker table for the wild-type minority, the group in which RNA sequencing pays for itself.
It is the proof that plasma genotyping can enrol patients for a targeted colorectal trial, which matters most for a 2 to 3% alteration where archival tissue is often exhausted or out of date.
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 shows that the driver frequencies quoted in Western guidelines are population statistics rather than facts about the disease, which matters for how many patients anywhere are expected to benefit from a given medicine.
It turned the laboratory prediction into a clinical rule: after a second-generation ALK inhibitor, genotype the tumour, and treat the absence of an ALK mutation as evidence that the cancer has stopped depending on ALK.
Shares Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4), Oncogene addiction, Gene fusion, ALK and the tags mechanism, mechanics-atlas.
Shares EGFR C797S, Assessment of resistance mechanisms and clinical implications in patients with EGFR T790M-positive lung cancer and acquired resistance to osimertinib, Amivantamab, Resistance routes: how a blocked pathway comes back and the tags mechanism, mechanics-atlas.
Shares Alectinib, Lorlatinib, ALK, Osimertinib and the tags mechanism, mechanics-atlas.
Shares Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers, Prostate cancer (KEGG map), Non-small cell lung cancer (KEGG map), Resistance routes: how a blocked pathway comes back and the tags mechanism, mechanics-atlas.
Shares ADCC (antibody-dependent cellular cytotoxicity), Cetuximab, Bispecific antibodies, Trastuzumab and the tags mechanism, mechanics-atlas.
Shares Lorlatinib, Resistance routes: how a blocked pathway comes back, ALK, Trastuzumab deruxtecan and the tags mechanism, mechanics-atlas.
Shares Genomic landscape of lung adenocarcinoma in East Asians, Genomic and evolutionary classification of lung cancer in never smokers, Triple-negative breast cancer (TNBC), Pancreatic ductal adenocarcinoma and the tags mechanism, mechanics-atlas.
Shares HGF, MET, KRAS, Pancreatic ductal adenocarcinoma and the tags mechanism, mechanics-atlas.