- Perspective
10 Pages
Complex diseases require therapeutic decisions that adapt as the disease evolves over time and in response to treatment. Current precision medicine remains largely centered on selecting an individual drug or predefined regimen from molecular characteristics measured at a particular time. The next evolution of precision medicine is toward adaptive therapeutic trajectories in which treatment decisions change over the course of treatment. Germline genomic information remains constant and contributes baseline susceptibility and pharmacogenomic information. By contrast, somatic alterations, multi-omic profiles, clinical state, and treatment response may change during disease progression and therapy and can inform subsequent treatment decisions. The volume and complexity of longitudinal molecular and clinical data exceed what can be integrated reliably by unaided human cognition. Artificial intelligence (AI) may help integrate these high-dimensional longitudinal data. The scientific challenge is whether AI-derived treatment recommendations are reliable and improve patient outcomes. This model raises a regulatory problem beyond conventional drug approval: how to evaluate a bounded therapeutic system in which patient-specific treatment recommendations change as the patient’s condition evolves.
J. Genome Biotechnol. Genet.
16 September 2026




![Cellular organization and multilevel regulation of epidermal pigmentation. (A) Schematic representation of the epidermal melanin unit, in which each melanocyte functionally interacts with multiple surrounding keratinocytes, and the sequential cellular processes underlying pigmentation. Melanosomes undergo progressive biogenesis and maturation through stages I–IV within melanocytes, accompanied by melanogenic enzyme loading and melanin deposition. Mature melanosomes are transported toward the dendrites by microtubule-dependent mechanisms and captured at the cell periphery through the Rab27A–melanophilin–myosin Va complex and actin-dependent machinery. Their transfer to keratinocytes may occur through several proposed, non-mutually exclusive mechanisms, including cytophagocytosis, shedding vesicles, membrane-associated transfer, and exocytosis followed by phagocytosis. After uptake, keratinocytes regulate pigment fate through intracellular redistribution, retention, lysosome-like storage, and degradation, while the organization of melanin into supranuclear caps contributes to nuclear photoprotection. (B) Environmental and paracrine modulation of epidermal pigmentation through ultraviolet radiation, inflammatory and hormonal signals, oxidative stress, aging, and dermal–epidermal crosstalk. Pigmentation is dynamically regulated by paracrine signals, environmental stimuli, and dermal–epidermal interactions, which collectively shape melanin production, transfer, and retention. Created in BioRender. Becerra, D. (2026) https://BioRender.com/hyn15da and adapted from published studies [2,4,35,36,38].](https://mdpi-res.com/cdn-cgi/image/width=281%2Cheight=192/https://mdpi-res.com/jgbg/jgbg-01-00014/article_deploy/html/images/jgbg-01-00014-g001-550.jpg)
![Historical foundations and the emergence of mezcal wine in 16th-century Western Mexico. The illustration depicts the ancestral origins of raicilla following the arrival of the Manila Galleon. The introduction of Asian distillation technology to the coasts of Colima and Nueva Galicia facilitated the processing of endemic Agave varieties into proto-mezcals, such as the wine of the hill “vino del cerro” originating in Talpa de Allende. From these common ancestors arose the modern raicilla, tuxca, bacanora, mezcal, and tequila industries [7,13,14,18].](https://mdpi-res.com/cdn-cgi/image/width=281%2Cheight=192/https://mdpi-res.com/jgbg/jgbg-01-00013/article_deploy/html/images/jgbg-01-00013-g001-550.jpg)