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PubMed2005

Novel left ventricular assist systems I and II for cardiac recovery: the driver.

We have recently described the Novel Left Ventricular Assist Systems (Novel LVAS) I and II, which avoid cannulation of cardiac chambers and synchronize pumping with the patient's electrocardiogram. We now describe the drive system in more detail. The drive unit is an air-driven pulsatile system. The driver's parameters can be programmed. This electro-pneumatic unit contains 3 modules. A remarkable feature of the driver system is that it contains 2 pneumatic units that alternate in their function every 15 minutes. This prevents overheating and component fatigue or failure, and it enables the use of smaller units. If one of the units fails, an alarm will warn of the problem, and the other will continue indefinitely. This LVAS is synchronized with the patient's ECG, which enables it to eject the stroke volume during diastole and in this way to act as a chronic counterpulsator. We have designed the Novel LVAS to operate at a low-frequency rate. This fact, together with the electrocardiographic synchronization, offers the best prospect for myocardial recovery in patients who are also receiving beta-adrenergic blocking agents. This dual therapy will help adjust heart rate to pump frequency.

Equipment Design↗

PubMed2007

The use of classroom training and simulation in the training of medical responders for airport disaster.

There is a dire need to have complementary form of disaster training which is cost effective, relatively easy to conduct, comprehensive, effective and acceptable. This will complement field drills training. A classroom-based training and simulation module was built by combining multiple tools: Powerpoint lectures, simulations utilising the Kuala Lumpur International Airport (KLIA) schematic module into 'floortop' model and video show of previous disaster drill. 76 participants made up of medical responders, categorised as Level 1 (specialists and doctors), Level 2 (paramedics), Level 3 (assistant paramedics) and Level 4 (health attendants and drivers) were trained using this module. A pre-test with validated questions on current airport disaster plans was carried out before the training. At the end of training, participants answered similar questions as post-test. Participants also answered questionnaire for assessment of training's acceptance. There was a mean rise from 47.3 (18.8%) to 84.0 (18.7%) in post-test (p<0.05). For Levels 1, 2, 3 and 4 the scores were 94.8 (6.3)%, 90.1 (11)%, 80.3 (20.1)% and 65 (23.4)% respectively. Nevertheless Level 4 group gained most increase in knowledge rise from baseline pre-test score (51.4%). Feedback from the questionnaire showed that the training module was highly acceptable. A classroom-based training can be enhanced with favourable results. The use of classroom training and simulation effectively improves the knowledge of disaster plan significantly on the back of its low cost, relatively-easy to conduct, fun and holistic nature. All Levels of participants (from specialists to drivers) can be grouped together for training. Classroom training and simulation can overcome the problem of "dead-document" phenomenon or "paper-plan syndrome".

Aviation↗

PubMed2005

Using eye movements to evaluate effects of driver age on risk perception in a driving simulator.

Novice drivers (16-year-olds with < or = 6 months' driving experience) have the highest crash involvement rates per 100 million vehicle miles (161 million vehicle km). In the past, this was attributed to greater risk taking or poorly developed psychomotor skills. More recently, however, their high crash involvement rate has been hypothesized to be attributable largely to their relative inability to acquire and assess information in inherently risky situations. The current study seeks to evaluate this hypothesis by recording eye movements while 72 participants (24 novice drivers, 24 younger drivers, and 24 older drivers) drove through 16 risky scenarios in an advanced driving simulator. There were significant age-related differences in driver scanning behavior, consistent with the hypothesis that novice drivers' scanning patterns reflect their failure to acquire information about potential risks and their consequent failure to deal with these risks. Actual or potential applications of this research include modification of these scenarios for display on a PC as a basis for a training module that would enable novice drivers to recognize risky scenarios before they encounter them on the road, in the hope of reducing their high fatality rate.

Accidents, Traffic↗

PubMed2004

Beat-wave excitation of plasma waves based on relativistic bistability.

A nonlinear beat-wave regime of plasma wave excitation is considered. Two beat-wave drivers are considered: intensity-modulated laser pulse and density-modulated (microbunched) electron beam. It is shown that a long beat-wave pulse can excite strong plasma waves in its wake even when the beat-wave frequency is detuned from the electron plasma frequency. The wake is caused by the dynamic bistability of the nonlinear plasma wave if the beat-wave amplitude exceeds the analytically calculated threshold. In the context of a microbunched beam driven plasma wakefield accelerator, this excitation regime can be applied to developing a femtosecond electron injector.

Journal Article↗

PubMed2000

Relative distribution of synapses in the A-laminae of the lateral geniculate nucleus of the cat.

Previous electron microscopic studies of synaptic terminal distributions in the lateral geniculate nucleus have been flawed by potential sampling biases favoring larger synapses. We have thus re-investigated this in the geniculate A-laminae of the cat with an algorithm to correct this sampling bias. We used serial reconstructions with the electron microscope to determine the size of each terminal and synaptic type. We observed that RL (retinal) terminals are largest, F (local, GABAergic, inhibitory) terminals are intermediate in size, and RS (cortical and brainstem) terminals are smallest. We also found that synapses from RL terminals are largest, and thus most oversampled, and we used synaptic size data to correct for sampling errors. Doing so, we found that the relative synaptic percentages overall are 11.7% for RL terminals, 27.5% for F, and 60.8% for RS. Furthermore, we distinguished between relay cells and interneurons with post-embedding immunocytochemistry for GABA (relay cells are GABA negative and interneurons are GABA positive). Onto relay cells, RL terminals contributed 7.1%, F terminals contributed 30.9%, and RS terminals contributed 62.0%. Onto interneurons, RL terminals contributed 48.7%, F terminals contributed 24.4%, and RS terminals contributed 26.9%. We also found that RL terminals included many more separate synaptic contact zones (9.1 +/- 1.6) than did F terminals (2.6 +/- 0.2) or RS terminals (1.02 +/- 0.02). We used these data plus the calculation of overall percentages of each synaptic type to compute the relative percentage of each terminal type in the neuropil: RL terminals represent 1.8%, F terminals represent 14.5%, and RS terminals represent 83.7%. We argue that this relative synaptic paucity is typical for driver inputs (from retina), whereas modulator inputs (all others) require many more synapses to achieve their function.

Algorithms↗

PubMed1980

Burst reset and frequency control of the neuronal oscillators in the cardiac ganglion of the crab, Portunus sanguinolentus.

1. The five large and four small neurones in the cardiac ganglion of the crab, Portunus, are electrotonically coupled and behave as a single relaxation oscillator, exhibiting periodic bursting activity in vitro. Recorded from the large neurone somata, this activity consists of 200-400 ms slow depolarizations called 'driver potentials' (Tazaki & Cooke, 1979a), accompanied by attenuated action potentials and EPSP's from small neurone input. 2. There is a strong positive correlation between the duration of the driver potential and the duration of the following interburst interval in the spontaneously active ganglion. This correlation is preserved during prolonged depolarization and hyperpolarization. 3. When a driver potential is prematurely terminated by an injected current pulse, the following interburst interval is shortened in direct proportion to the decrease in driver potential duration. 4. When a driver potential or a burst of high-frequency action potential activity is evoked by a depolarizing current pulse, the cardiac oscillator resets to the point of maximum hyperpolarization of the burst cycle, and the following interburst interval is of normal duration. Resetting following an evoked driver potential is complete. Partial resetting occurs only after short, evoked action potential bursts in the absence of a driver potential. 5. Reset of the oscillator causes phase shifts in the subsequent cycles of activity, which vary with the phase of application and duration of the injected current pulse. Response curves have been constructed for a comprehensive range of durations and intensities of hyperpolarizing and depolarizing current pulses applied at all phases of the oscillator cycle. 6. The phase shifts are composed of contributions from the duration of the current pulse, from the premature initiation of the slow depolarizing pacemaker potential due to early termination of the burst, and from the change in interburst interval correlated with truncation of the driver potential. 7. Considering the cardiac ganglion as a relaxation oscillator, frequencey control by entrainment to periodically applied current pulses was quantitatively predicted from the phase-response curves and experimentally confirmed. 8. A high concentration (10(-5) M) of octopamine can inhibit driver potential activity in the large neurones. This was used to examine possible frequency modulating effects of electrotonic feedback from the large neurone driver potentials onto the small neurone pacemaker activity. 9. The observations are discussed in relation to the ionic model for driver potentials and slow pacemaker potential activity in the cardiac ganglion, as proposed by Tazaki & Cooke (1979a, b).

Action Potentials↗

PubMed2002

An under-hand steering wheel grasp produces significant injury risk to the upper extremity during airbag deployment.

Recent laboratory investigations suggest that a deploying airbag may fracture the forearm. These studies positioned the arm in an overhand grasp placing the forearm over the airbag module. However, there is little published data on how drivers grip the steering wheel and the general proximity of the upper extremity to the airbag module. The objective of the current study was to identify 'real world' upper extremity positions and to correlate these with accident and experimental data. A survey of the National Automotive Sampling System (NASS) for the years 1995-99 revealed an increase in the number of forearm fractures due to driver-airbag interaction. As NASS does not provide the position of the forearm, common upper extremity positions were identified in a volunteer driving population. These positions were simulated using a specially instrumented 50(th) percentile male dummy to determine the relative injury risk for the different positions. Analysis showed that an under hand grasp of the wheel turned 90 degrees yielded the highest magnitude impact event. This single position was then simulated in 9 cadaver experiments. Dual stage airbag deployments produced forearm fractures in 2 arms. Experiments using the contralateral arms from the fractured subjects with a single stage airbag deployment produced no fractures. Analysis of forearm kinematics suggests that increasing forearm velocity and thus, acceleration exposure, is associated with forearm injury. Further, the data suggests that reductions in acceleration exposure via reduced airbag inflation decreased the apparent risk of forearm fracture.

Adult↗

PubMed2026

Mov10 mitigates hematopoietic stem cell exhaustion under stress by modulating the Camp-mediated inflammatory pathway.

The integrity of hematopoietic stem cell (HSC) function is crucial for robust hematopoietic regeneration following stress. Inflammatory responses are pivotal drivers of HSC stress response, yet the precise modulation of inflammatory pathways remains incompletely defined. In this study, we identify the RNA helicase Mov10 as a negative regulator of stress-induced inflammatory pathways in HSC. Our study indicates that Mov10, which is critically required for HSC maintenance, is highly expressed in HSC, and its loss adversely affects HSC fitness and survival during hematopoietic stress induced by bone marrow transplantation and irradiation (IR). Mechanistically, Mov10 mitigates excessive inflammatory activation to sustain HSC functional integrity during hematopoietic stress, primarily by enhancing the translation of CAMP, which inhibits the interaction between TNF-α and its receptor TNFR1 and suppresses NF-κB activation. Overall, our results imply that Mov10 plays a critical role in averting functional failure of hematopoiesis under stress, presenting viable paths for the therapeutic intervention of relevant diseases.

Camp↗

PubMed2026

ABCB1 Polymorphisms Influence on Temozolomide Resistance and Overall Survival in Glioblastoma Patients: A Systematic Review of Clinical Evidence.

Glioblastoma (GB), defined as IDH-wildtype CNS WHO grade 4 tumour according to the 2021 WHO classification of CNS tumours, remains a uniformly lethal malignancy in which the efficacy of temozolomide (TMZ) continues to be constrained by both intrinsic tumur biology and the pharmacological barrier imposed by the blood-brain barrier (BBB). Given the central role of the ABCB1 (MDR1/P-glycoprotein) efflux transporter in regulating CNS drug disposition, germline variation in ABCB1 has been proposed as a potential determinant of interindividual variability in TMZ response. This systematic review synthesised clinical evidence from four independent studies, encompassing more than 400 GB patients, evaluating the association between ABCB1 polymorphisms and TMZ efficacy and patients' survival. Across the available literature, the influence of ABCB1 genetic variation emerged as limited and inconsistent. An early study reported a marked survival advantage for carriers of the ABCB1 C1236T C/C genotype treated with TMZ, suggesting reduced efflux and enhanced drug exposure. However, subsequent investigations, including epigenetic analyses, high-quality multivariate survival modelling and a pharmacokinetic study demonstrating genotype-dependent differences in plasma TMZ concentrations, did not replicate a corresponding survival effect. Across the remaining cohorts, common variants such as 1236C>T, 2677G>T/A, 3435C>T and 1199G>A showed no robust association with clinical outcome, indicating that transporter-mediated modulation is likely overshadowed by dominant prognostic drivers, including MGMT methylation, IDH status and tumour heterogeneity. Collectively, current evidence does not support ABCB1 polymorphisms as reliable predictive biomarkers of TMZ response in GB. Nonetheless, the pharmacokinetic signals observed, together with emerging technologies capable of selectively modulating efflux activity at the tumour-BBB interface, point to a continued role for ABCB1 in future therapeutic strategies. Integration of transporter genomics with spatial pharmacokinetics and molecular stratification will be essential to refine drug delivery and improve outcomes in GB.

Humans↗

PubMed2026

CRISPR screening reveals NPC1L1 as a key driver of glioblastoma progression via cholesterol metabolic regulation.

Glioblastoma (GBM), the most aggressive central nervous system (CNS) malignancy, currently lacks curative therapeutic options. While immunotherapy has revolutionized treatment for many cancers, GBM remains refractory to immune-based interventions due to the absence of effective immunotherapeutic targets. Here, through CRISPR screening, we identify Niemann-Pick C1-like 1 (NPC1L1) as a previously unrecognized key driver of GBM progression. Mechanistically, NPC1L1 modulates cholesterol metabolism to concurrently enhance tumor cell stemness and suppress CD8+ T-cell activation, thus inducing tumor progression. Notably, combined treatment with ezetimibe (NPC1L1 inhibitor) and anti-PD-1 antibody elicited potent antitumor activity in GBM orthotopic mouse models. Collectively, these findings establish NPC1L1 as a critical regulator of GBM pathogenesis, underscoring the translational potential of targeting NPC1L1-mediated cholesterol metabolism for developing novel GBM immunotherapies.

Humans↗

PubMed2026

Integrated transcriptomic and functional characterization of Claudin-1 reveals its oncogenic and immunomodulatory roles in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) remains among the deadliest malignancies, driven by its invasive nature and lack of effective biomarkers. Disruption of the epithelial barrier, mediated by tight junction components, is a critical yet underexplored contributor to PDAC progression. Claudins, integral regulators of tight junction integrity, display altered expression across cancers, but their prognostic and immunomodulatory roles in PDAC remain unclear. We performed an integrative analysis of 177 RNA-Seq datasets from TCGA and GTEx to characterize Claudin family alterations in PDAC. Differential expression, copy number variation, methylation, and co-expression networks were analyzed alongside clinical and survival data. Prognostic significance was assessed using Kaplan - Meier and Cox regression analyses, while immune cell infiltration was examined using deconvolution algorithms. Functional validation of Claudin-1 was conducted in Capan-1 cells using CRISPR/Cas9 knockout, followed by proliferation, wound-healing, and Western blot assays. Ten Claudin genes were significantly dysregulated, with Claudin-1 and Claudin-4 frequently amplified and associated with advanced stage and poor survival. High Claudin-1 expression correlated with reduced immune infiltration, indicating an immune-excluded phenotype characterized by immune cells retained in the tumor stroma but largely absent from the tumor parenchyma. Claudin-1 knockout markedly inhibited proliferation, migration, and EMT, evidenced by downregulation of Snail and Slug and restoration of E-cadherin expression. This integrative transcriptomic and functional study identifies Claudin-1 as a key driver of PDAC aggressiveness and immune modulation. These findings establish Claudin-1 as a promising prognostic biomarker and therapeutic target for restoring epithelial integrity and counteracting immune evasion in pancreatic cancer.

Humans↗

PubMed2005

Drivers of brain plasticity.

PURPOSE OF REVIEW: Neural plasticity represents a crucial mechanism of the human brain to adapt to environmental changes in the developing and adult human central nervous system. This property of the central nervous system contributes to learning and functional recovery from neurological diseases such as stroke. Novel interventional approaches have been proposed and are under investigation to modulate neural plasticity, enhance it when it plays an adaptive role and downregulate it when it is considered maladaptive. RECENT FINDINGS: One of the purposes of research in neurorehabilitation has been to develop interventional approaches to enhance the beneficial effects of training. Procedures like cortical stimulation, administration of central nervous system active drugs and modulation of afferent input have been evaluated as drivers of neural plasticity in healthy subjects and in small groups of patients with stroke. So far, these studies have shown promising results and translation into the clinic is under investigation. SUMMARY: Cortical stimulation and purposeful changes in afferent input that modulate neural plasticity impact on behavioral markers of performance, learning and functional recovery and represent promising tools in neurorehabilitation.

Animals↗

PubMed2026

Transcriptomic signatures of mind-body transformations therapy in breast cancer: Downregulation of the interferon signaling pathway.

BACKGROUND: Growing evidence has shown that Mind-Body Transformations-Therapies (MBT-T) are able to modulate chronic inflammation, a well-known driver of cancer progression and drug resistance. In our previous work, we showed that a specific MBT-T protocol was able to reduce the release of various pro-inflammatory cytokines and chemokines in the sera of patients with breast cancer that completed adjuvant chemotherapy. Despite these clinical observations, the underlying molecular pathways through which this therapy exerts its effects remain unclear. This study aims to address this gap by characterizing genome-wide transcriptional profiles in patients undergoing a novel MBT-T protocol. METHODS: In this proof-of-concept study, patients with breast cancer were randomized into two groups: Group 1 (CTL), receiving standard follow-up care, and Group 2 (MBT-T), receiving standard follow-up plus biweekly MBT-T for 4 months. Blood samples were collected at different timepoints during the treatment. After RNA extraction from whole blood, gene expression was analyzed on twenty-one patients (CTL, n = 7; MBT-T, n = 14) using the nCounter® Human Inflammation Panel (249 genes). RESULTS: Patients undergoing MBT-T showed a significant global downregulation of inflammatory gene expression compared to the control group. The analysis revealed that the Interferon (IFN) signaling pathway was the most significantly suppressed, by downregulation of key genes such as IFIT1, IFIT3, IFI44, MX1 and OASL in the MBT-T group. CONCLUSIONS: MBT-T acts as a biological modulator capable of downregulating key inflammatory pathways at the transcriptional level. These findings provide a genomic basis for the clinical benefits of mind-body interventions in oncology.

Breast cancer↗

PubMed2026

CDC20B Dysregulation: Links to Tumor Prognosis and Immunity.

OBJECTIVE: This study aimed to clarify the pan-cancer expression pattern, upstream regulatory mechanisms, prognostic relevance, and immune associations of CDC20B. METHOD: Using public databases (GTEx, GEO, and TCGA), we examined CDC20B expression and its associations with prognosis and tumor immunity across multiple cancers. Immunohistochemistry (IHC) on an independent clinical cohort was performed to validate CDC20B upregulation in tumor tissues. Promoter methylation, genetic alterations, and immune infiltration were analyzed using bioinformatics tools (cBioPortal, UALCAN, TIMER2.0, ESTIMATE). Functional enrichment was assessed by GSEA and single-cell state analysis (CancerSEA). RESULTS: CDC20B was markedly upregulated in most tumor types (p < 0.001), with strong diagnostic efficiency (AUC > 0.7 in 15 cancers) and potential regulation by promoter hypomethylation. IHC confirmed its overexpression in clinical tumor tissues. However, the prognostic impact of CDC20B was cancer-type-specific: high expression correlated with poor overall survival in UCS, LGG, KIRC, and OV, but with favorable survival in BRCA, LUAD, and PAAD. CDC20B expression was associated with immune infiltration patterns, showing negative correlations with ImmuneScore in most cancers but positive correlations with CD8+ T cells in PAAD. Functional analyses indicated involvement in EMT, KRAS/NF-κB signaling, and DNA damage response pathways. DISCUSSION: The dual prognostic role of CDC20B suggests context-dependent functions, likely influenced by tumor microenvironment composition and underlying oncogenic programs. Promoter hypomethylation emerges as a potential epigenetic driver of overexpression. The associations with immune modulation and genomic instability suggest that CDC20B is a candidate biomarker, though causal relationships require experimental validation. CONCLUSION: CDC20B may contribute to tumor progression in a context-dependent manner, with its prognostic impact varying across cancer types. Its role in tumor immunity and oncogenic pathways warrants further investigation, particularly in stratified patient populations.

CDC20B↗

PubMed2002

Relative distribution of synapses in the pulvinar nucleus of the cat: implications regarding the "driver/modulator" theory of thalamic function.

To provide a quantitative comparison of the synaptic organization of "first-order" and "higher-order" thalamic nuclei, we followed bias-corrected sampling methods identical to a previous study of the cat dorsal lateral geniculate nucleus (dLGN; Van Horn et al. [2000] J. Comp. Neurol. 416:509-520) to examine the distribution of terminal types within the cat pulvinar nucleus. We observed the following distribution of synaptic contacts: large terminals that contain loosely packed round vesicles (RL profiles), 3.5%; presynaptic profiles that contain densely packed pleomorphic vesicles (F1 profiles), 7.3%; profiles that could be both presynaptic and postsynaptic that contain loosely packed pleomorphic vesicles (F2 profiles), 5.0%; and small terminals that contain densely packed round vesicles (RS profiles), 84.2%. Postembedding immunocytochemistry for gamma-aminobutyric acid (GABA) was used to distinguish the postsynaptic targets as thalamocortical cells or interneurons. The distribution of synaptic contacts on thalamocortical cells was as follows: RL profiles, 2.1%; F1 profiles, 6.9%; F2 profiles, 5.4%; and RS profiles, 85.6%. The distribution of synaptic contacts on interneurons was as follows: RL profiles, 11.8%; F1 profiles, 9.7%; F2 profiles, 2.8%; and RS profiles, 75.6%. These distributions are similar to that found within the dLGN in that the RS inputs (the presumed "modulators") far outnumber the RL inputs (the presumed "drivers"). However, in comparison to the dLGN, the pulvinar nucleus receives significantly fewer numbers of RL, F1, and F2 contacts and significantly higher numbers of RS contacts. Thus, the RS/RL synapse ratio in the pulvinar nucleus is 24:1, in contrast to the 5:1 RS/RL synapse ratio in the dLGN (Van Horn et al., 2000). In first-order nuclei, the lower RS/RL synapse ratio may result in the transfer of visual information that is largely unmodified. In contrast, in higher-order nuclei, the higher RS/RL synapse ratio may allow for a finer modulation of driving inputs.

Animals↗

PubMed1981

Comment: a schema for the interactions between motor programs and sensory input.

In this overview we utilize and extend a model, originally developed for "command interneuron" control of the generation of motor programs, to discuss the roles sensory inputs play in movement control. To provide a conceptual framework, we present a modular schematic of the motor control and sensory processing apparatus of an hypothetical nervous system. In the schematic, "subroutines" (basic units of motor programs) are seen as "playing out" through switching and sequencing networks to "driver neurons." The "driver neurons" then activate motoneurons to execute the programmed movements. Five modes of interaction between motor programs and sensory input are considered using examples from invertebrate and vertebrate neuronal circuitry. These modes of interaction occur at the following locations: (1) the "program selector," to initiate a motor program; (2) the "motor subroutine directory," advancing the program to the next subroutine; (3) the "driver neurons" and motoneurons, where the "gain" of subroutine instructions can be modulated; (4) the "motor programmer," which monitors programs in progress and provides for program development and updating; and (5) the "driver neurons" themselves, which control sensory processing by "selecting" the appropriate sensory inputs for the program in progress. Mode 5 is illustrated in more detail through a consideration of the modification of stretch receptor input by "extensor" and "flexor" command interneurones in the circuitry controlling postural movements of the crayfish abdomen.

Humans↗

PubMed2005

Spatial control of high-harmonic generation in hollow fibers.

We demonstrate the control of high-harmonic generation in a hollow fiber by shaping the spatial structure of the generating laser pulse. We use a liquid-crystal-based two-dimensional spatial light modulator to control the spatial phase of the driver pulse. An evolutionary algorithm finds the spatial laser phase distribution that is optimal for reaching maximum total harmonic yield and for selectively enhancing the cutoff region of the spectrum. We show that enhacement of harmonic generation is related to coupling into a single fiber mode. Our results directly show that spatial properties of the laser are important parameters in fully controlling the high-harmonic spectrum. It is thus not possible to derive the controllability of the high-harmonic generation from the single-atom response only.

Journal Article↗

PubMed2026

MET-Aberrant non-small cell lung cancer: from kinase dependence to cell-surface targetability-mechanistic basis and biomarker framework for bispecific antibodies and antibody-drug conjugates.

MET-aberrant non-small cell lung cancer (NSCLC) is not a uniform therapeutic entity. Its biology, diagnostic pathways, and treatment sensitivity differ across MET exon 14 skipping alteration (METex14), MET amplification, and MET overexpression. This heterogeneity cannot be fully explained by conventional event-based classification and is reflected in the distinct clinical activity of MET tyrosine kinase inhibitors (MET-TKIs), bispecific antibodies (BsAbs), and antibody-drug conjugates (ADCs). With the emergence of antibody-based therapies, MET has evolved from a signaling driver to a cell-surface target for receptor modulation and payload delivery. We therefore propose a clinically anchored two-dimensional framework for interpreting therapeutic relevance in MET-aberrant NSCLC: kinase dependence and cell-surface targetability. Neither dimension should be regarded as a directly measurable binary variable. Kinase dependence is inferred from genomic and treatment-contextual proxies, most strongly METex14 and, more conditionally, high-level focal MET amplification. Cell-surface targetability is approximated by drug-specific IHC assessment of assay-defined c-MET protein expression; however, receptor internalization, intracellular trafficking, and payload delivery capacity remain incompletely measurable in routine clinical practice. Within this framework, MET-TKIs have the most evidence-supported established role in tumors with evidence of MET-driven kinase dependence. EGFR × MET BsAbs have demonstrated clinical activity in broad post-osimertinib EGFR-mutant NSCLC, while EGFR/MET co-dependence or MET-mediated bypass activation provides a mechanistic rationale for their use; MET-defined preferential benefit remains to be prospectively established. MET-directed antibody-drug conjugates (MET-ADCs) are supported in drug- and assay-defined populations with high c-MET protein overexpression, although the predictive relevance of delivery-related factors remains hypothesis-generating. Accordingly, MET testing should shift from single-event detection to platform-oriented stratification: next-generation sequencing (NGS) for driver alterations and resistance profiles, fluorescence in situ hybridization (FISH) for high-level focal amplification, and immunohistochemistry (IHC) for surface expression relevant to antibody-based therapies. This framework is intended to organize current biological and clinical evidence rather than to replace drug-specific companion diagnostics, regulatory indications, or prospectively validated treatment-selection algorithms. Precision treatment of MET-aberrant NSCLC is thus moving from event-based drug selection toward mechanism-based therapeutic matching. Future priorities include standardizing biomarkers, defining optimal target populations, and aligning biological subtypes, diagnostic strategies, and therapeutic platforms.

Antibody-drug conjugate↗