Cancer / Oncology/KRAS-driven NSCLC
Thoracic · subtype
KRAS-driven NSCLC
Subtype of Non-small-cell lung cancer
Clinical / Scientific
KRAS mutations lock (and sometimes ) on. G12C has allele-specific inhibitors; co-mutations in STK11 or KEAP1 alter immune and metabolic phenotype. Direct RAS targeting is evolving and still not universal across alleles.
Core Biological Drivers
KRAS mutation
GTPase lock.
STK11 / KEAP1 co-mutation
Metabolic and NRF2 context.
Key Pathways
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
Aerobic (Warburg metabolism) supports ATP, biomass and redox buffering even when oxygen is available. Hexokinase, PKM2 and lactate export are frequent nodes.
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.
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.
Mitochondrial stress
Electron-transport stress raises ROS; NRF2-driven transcription can buffer that stress and support survival. Antioxidant interventions are dual-edged.
Energy stress
Energetic stress activates AMPK, which can restrain mTORC1. Biguanides and related tools map onto this axis in models.
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.
Glutamine anaplerosis and nucleotide nitrogen demand are prominent in MYC-high and rapidly proliferating tumours. Dependence is heterogeneous.
Tumor Microenvironment
Tumour-associated macrophages and myeloid-derived suppressor cells secrete cytokines that support invasion and blunt cytotoxic T cells.
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
Adaptive reactivation, allele-specific resistance, and immune-cold co-mutant states.
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.
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.
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.
Berberine
Target / Mechanism
Isoquinoline alkaloid that can inhibit complex I and activate in metabolic models, with additional -independent reports. Not an approved antineoplastic.
Cancer relevance
Complex I / pharmacology overlaps metformin-like energy stress in models. Bioavailability and lack of oncology indication keep this mechanistic.
Metabolic energy-stress hypothesis. Convergence: AMPK, mTOR, Mitochondrial oxidative phosphorylation.
Research Context
- Hallmarks. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674. https://doi.org/10.1016/j.cell.2011.02.013
- 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.