The emergence of high-throughput approaches has had a profound impact on personalized medicine, evolving the identification of inheritable variation to trajectory analyses of transient states and paving the way for the unveiling of response biomarkers. The utilization of the multi-layered pharmaco-omics data, including genomics, transcriptomics, proteomics, and relevant biological information, has facilitated the identification of key molecular biomarkers that can predict the response to therapy, thereby optimizing treatment regiments and providing the framework for a tailored treatment plan. Despite the availability of multiple therapeutic options for chronic diseases, the highly heterogeneous clinical response hinders the alleviation of disease signals and exacerbates the annual burden and cost of hospitalization and drug regimens. This review aimed to examine the current state of the pharmaco-omic approaches performed in psoriasis, a common inflammatory disease of the skin. We sought to identify central studies that investigate the inter-individual variability and explore the underlying molecular mechanisms of drug response progression via biological profiling in psoriatic patients administered with the extended therapeutic armamentarium of psoriasis, incorporating conventional therapies, small molecules, as well as biological drugs that inhibit central pathogenic cytokines involved in the disease pathogenesis.

Despite the increasing research and clinical interest in the predisposition of psoriasis, a chronic inflammatory skin disease, the multitude of genetic and environmental factors involved in its pathogenesis remain unclear. This complexity is further exacerbated by the several cell types that are implicated in Psoriasis’s progression, including keratinocytes, melanocytes and various immune cell types. The observed interactions between the genetic substrate and the environment lead to epigenetic alterations that directly or indirectly affect gene expression. Changes in DNA methylation and histone modifications that alter DNA-binding site accessibility, as well as non-coding RNAs implicated in the post-transcriptional regulation, are mechanisms of gene transcriptional activity modification and therefore affect the pathways involved in the pathogenesis of Psoriasis. In this review, we summarize the research conducted on the environmental factors contributing to the disease onset, epigenetic modifications and non-coding RNAs exhibiting deregulation in Psoriasis, and we further categorize them based on the under-study cell types. We also assess the recent literature considering therapeutic applications targeting molecules that compromise the epigenome, as a way to suppress the inflammatory cutaneous cascade.