Cancer / Oncology/MET-altered NSCLC
Thoracic · subtype
MET-altered NSCLC
Subtype of Non-small-cell lung cancer
Clinical / Scientific
MET exon 14 skipping or amplification drives MET–/ signalling, as a primary driver or EGFR-resistance bypass.
Core Biological Drivers
MET exon 14 / amplification
MET addiction.
Key Pathways
Scientific explanation
The RAS–RAF–MEK–ERK cascade transmits mitogenic RTK signals to programmes for proliferation and differentiation.
Scientific explanation
phosphorylates PIP2 to PIP3, recruiting . supports growth, survival, glucose uptake and mTORC1 input. Pathway activation is common via PIK3CA mutation, PTEN loss or -tyrosine- signalling.
Scientific explanation
Epithelial–mesenchymal plasticity, driven by TWIST/SNAIL/ZEB and TGF-β/Wnt/Notch inputs, reduces adhesion and increases motility and stem-like features.
Pathway Convergence
Target → pathway → downstream effect → biological consequence. Shared intersections are mechanistic maps, not protocols.
Growth-factor signalling
Ligand or mutation-driven RTK input feeds PI3K/AKT and mTORC1, supporting anabolic growth. This is a map of signalling, not a treatment protocol.
Metabolic Vulnerabilities
Aerobic supports ATP, biomass and acidification even when oxygen is available. Extent varies by tumour and remains a vulnerability hypothesis rather than a uniform target.
Tumor Microenvironment
Disordered vasculature creates , HIF-1α stabilization, induction and immune-suppressive adenosine/lactate milieus.
Metastasis Module
, protease-mediated invasion, , circulating tumour-cell survival and organ-specific colonization form the metastatic cascade. Pre-metastatic niches and vascular permeability influence tropism.
Resistance Biology
On-target MET mutations and parallel EGFR/KRAS reactivation.
Cancer Stemness
Wnt, Notch, Hedgehog, ALDH and CD44-associated programmes can mark stem-like fractions with quiescence and therapy tolerance. These markers are not interchangeable across tumour types.
Mechanism-Based Adjunctive Strategies
Compounds appear only where a mechanistic overlap exists for this cancer. Evidence tiers are not equivalent. Nothing here is a treatment recommendation.
Target / Mechanism
Modest complex I inhibition raises AMP:ATP, activating and restraining hepatic and -linked anabolism. Direct antineoplastic efficacy is not established from that pharmacology alone.
Cancer relevance
activation and restraint provide a metabolic rationale in - and -linked tumours. Human data are mixed and do not establish metformin as cancer therapy.
Metabolic adjunctive research context. Convergence: AMPK, mTOR, Glycolysis.
Target / Mechanism
Tetracycline antibiotic that can inhibit matrix metalloproteinases and, at experimental exposures, protein synthesis. Oncology uses remain investigational.
Cancer relevance
MMP inhibition and experimental effects map to invasion and stem-like states in models.
Anti-invasive / mitochondrial experimental context. Convergence: Invasion, Cancer stemness, Mitochondrial oxidative phosphorylation.
Research Context
- Resistance. Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer. 2013;13(10):714-726. https://doi.org/10.1038/nrc3599
This oncology atlas is educational. Pathway maps, adjunctive strategies, and compound listings describe mechanistic relevance. They do not establish clinical efficacy, do not recommend treatment, and are not a substitute for oncology care. Evidence tiers are not equivalent.