## 4 Discussion
Aberrant activation of _MAP2K2_ has been linked to various cancers, particularly melanoma and colorectal cancer, making it a validated target for anti-cancer therapies [75; 76]. The pharmacological inhibition of _MAP2K2_ has shown potential in overcoming resistance to upstream oncogenes such as _BRAF_ and _RAS_, and it remains to be tested if lycopene can have synergistic effects with these established _MAP2K2_ inhibitors to achieve optimal pharmacodynamic outcomes while minimising any potential adverse effects. Interestingly, _SCN3A_, a voltage-gated sodium channel, showed unique expression in the heart, pointing to possible roles in cardiac excitability, supporting prior studies reporting cardiovascular benefits of lycopene via electrophysiological and anti-inflammatory mechanisms [77]. _SCN3A_ is predominantly expressed in the central nervous system, where it is essential for the initiation and propagation of action potentials in neurons. Dysregulation or mutations in _SCN3A_ are associated with neurological disorders including epilepsy, developmental and epileptic encephalopathies, and cognitive impairments. _SCN3A_ represents a target for anticonvulsant development and therapies aimed at modulating neuronal excitability [78; 79]. Based on our findings, there seems to be merit in assessing the potential of lycopene in connecting the heart-brain axis via _SCN3A_ targeting. _TOP2A_ and _TRIM24_ have a vital role in DNA replication, transcription, and chromosome segregation and are well-established targets in cancer chemotherapy especially in breast, prostate, and liver cancers [80; 81]. Our report of the high-affinity targeting of _TOP2A_ and _TRIM24_ opens avenues for synergistically improving the pharmacodynamics of currently used chemotherapeutics (etoposide and doxorubicin) with lycopene. While this study provides a comprehensive computational analysis to identify potential targets of lycopene, it is important to note that the findings are primarily based on in silico predictions. Although tissue expression and pharmacokinetic properties were considered to enhance biological plausibility, experimental validation such as an in vitro or in vivo study was beyond the current scope. This represents a key limitation, and future studies are necessary to empirically validate the predicted targets and elucidate their mechanistic roles in lycopene's biological activity. Additionally, the use of CA ratios is based on simplified pharmacokinetic assumptions and does not capture the dynamic nature of biological systems; as such, these estimates should be interpreted as preliminary indicators rather than definitive measures of pharmacodynamic feasibility. Collectively, our findings suggest _MAP2K2_ and _SCN2A_ as the most pharmacologically plausible direct targets of lycopene in humans. Their strong affinity, favourable CA ratios, and wide tissue expression profiles suggest that these targets have a foundational role in mediating lycopene's pharmacological actions. Additional targets such as _TRIM24_, _TOP2A_, and _NTRK_ family members, while displaying lower CA ratios, may contribute to lycopene's broader systems-level impact, particularly in the context of inflammation, cancer biology, and neuroprotection. These multi-target interactions are consistent with lycopene's observed pleiotropic benefits in clinical and preclinical models [7; 30; 37; 45; 82]. In conclusion, our study advances the mechanistic understanding of lycopene pharmacology by integrating affinity profiling, network analysis, and expression mapping. While the hydrophobicity and relatively low systemic concentrations of lycopene pose challenges for classical drug-likeness, its selective interaction with key signalling and nuclear proteins highlights its potential as a nutraceutical agent with systems-level effects, which merits advancing its use for therapeutic applications. Future studies should aim to validate these interactions in functional cellular assays and assess tissue-specific accumulation patterns to better delineate lycopene's therapeutic potential.