Cancer / Oncology/Non-small-cell lung cancer
Thoracic · type
Non-small-cell lung cancer
Subtype of Lung cancer
Clinical / Scientific
NSCLC includes adenocarcinoma and squamous carcinoma. Adenocarcinoma is enriched for targetable drivers; squamous disease more often shows , SOX2 and oxidative-stress programmes. Checkpoint inhibitors are established in selected unselected-driver populations.
Molecular / histological subtypes
Core Biological Drivers
EGFR / ALK / ROS1 / MET / RET / BRAF / KRAS
Genotype-defined subsets.
KEAP1/NFE2L2
NRF2 stabilization.
PD-L1 / TMB context
Immune-evasion and visbility.
Key Pathways
Scientific explanation
EGFR is an ERBB-family tyrosine . Ligand activation or mutation (notably NSCLC exon 19/L858R) drives and signalling.
Scientific explanation
RAS GTPases and RAF kinases are frequent oncogenic nodes. KRAS, NRAS and BRAF mutations lock mitogenic signalling on in a ligand-independent way in many tumours.
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
NRF2/KEAP1 controls antioxidant and detoxification . KEAP1 or NFE2L2 mutations in lung and other cancers stabilize NRF2 and can confer therapy resilience.
Scientific explanation
PD-1 on T cells engaging PD-L1/PD-L2 restrains cytotoxic function. Tumour or myeloid PD-L1 is a canonical adaptive immune-evasion axis.
Scientific explanation
Aerobic (Warburg metabolism) supports ATP, biomass and redox buffering even when oxygen is available. Hexokinase, PKM2 and lactate export are frequent nodes.
Scientific explanation
family ligands drive endothelial sprouting and vascular permeability, a canonical tumour axis.
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.
Scientific explanation
recycles organelles and can support survival under nutrient or therapy stress. Context determines tumour-suppressive versus therapy-protective roles.
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.
Hypoxia to vessels
Low oxygen stabilizes HIF-1α, inducing VEGF and endothelial sprouting. Anti-angiogenic pharmacology intersects this axis but does not erase the tumour ecosystem.
Mitochondrial stress
Electron-transport stress raises ROS; NRF2-driven transcription can buffer that stress and support survival. Antioxidant interventions are dual-edged.
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.
STK11/LKB1-mutant KRAS tumours show metabolic and immune-cold features.
Tumor Microenvironment
Disordered vasculature creates , HIF-1α stabilization, induction and immune-suppressive adenosine/lactate milieus.
Tumour-associated macrophages and myeloid-derived suppressor cells secrete cytokines that support invasion and blunt cytotoxic T cells.
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 secondary mutations (e.g. EGFR T790M historically, C797S), bypass MET/HER2, histological transformation to SCLC, and efflux contribute.
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
Azole antifungal; off-target reports include Hedgehog-pathway antagonism and anti-angiogenic endothelial effects in experimental and early clinical settings. Not a licensed antineoplastic.
Cancer relevance
Hedgehog antagonism and anti-angiogenic endothelial reports exist, including early clinical probes. Not a licensed antineoplastic.
Hedgehog / angiogenesis research. Convergence: Hedgehog, Angiogenesis.
Target / Mechanism
Benzimidazole that binds β-. Mammalian disruption, mitotic arrest and related signalling in cancer models are preclinical and are not an approved anticancer use.
Cancer relevance
disruption can trigger mitotic stress and in cell and animal models. This is not an established oncology use.
Experimental antimitotic / microtubule stress. Convergence: Apoptosis, p53.
Target / Mechanism
Lysosomotropic agent that raises endosomal/autophagosomal pH, impairing flux. Combination trials in oncology have been mixed; blockade is not equivalent to proven benefit.
Cancer relevance
Lysosomal pH elevation impairs flux. Early combination trials exist; benefit is not established and toxicity/retinal risk remain labelled concerns.
Autophagy-modulation research combinations. Convergence: Autophagy.
Sulforaphane
Target / Mechanism
Isothiocyanate that can activate NRF2 via KEAP1 modification and has epigenetic HDAC-related reports in models. Chemoprevention hypotheses exceed proven oncology treatment.
Cancer relevance
KEAP1/NRF2 activation and epigenetic reports in models. Chemoprevention hypotheses are not treatment proof.
NRF2 / chemoprevention research. Convergence: NRF2, Oxidative stress.
Statins (HMG-CoA reductase inhibitors)
Target / Mechanism
Inhibit HMG-CoA reductase, depleting mevalonate-pathway isoprenoids needed for RAS/RHO prenylation and some sterol-dependent growth programmes. Observational oncology signals are mixed and not a licence to treat cancer with statins.
Cancer relevance
Mevalonate-pathway blockade can affect prenylation of RAS-family GTPases. Observational human signals are mixed and confounding is substantial.
Mevalonate / prenylation mechanistic overlap. Convergence: RAS/RAF, Fatty-acid metabolism.
Curcumin
Target / Mechanism
Polyphenol with promiscuous in-vitro NF-κB, and ROS effects. Bioavailability is poor; dish activity does not establish clinical anticancer efficacy.
Cancer relevance
In-vitro NF-κB/ effects are frequent. Poor bioavailability and absence of robust clinical anticancer efficacy keep this pathway-level.
Inflammatory-signalling dish models. Convergence: NF-κB, JAK/STAT.
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
- EGFR NSCLC. Lynch TJ, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350(21):2129-2139. https://doi.org/10.1056/NEJMoa040938
- ALK. Soda M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448(7153):561-566. https://doi.org/10.1038/nature05945
- Checkpoints. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252-264. https://doi.org/10.1038/nrc3239
- 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.