# The Immunogenetics of Psoriasis and Implications for Drug Repositioning
## 3 Implications for Drug Repositioning  
Soriasis treatments mainly aim to eliminate skin damage and prevent recurrence. Patients suffering from mild psoriasis are treated with local drugs and targeted light therapy. Patients with more severe forms of psoriasis undergo systemic treatments, such as a combination of methotrexate and phototherapy. However, its long-term use is hampered by safety issues. Understanding the progress of psoriatic immunogenetics is crucial in developingotherapies that target the immune system, ideally for patients with intensive forms of the disease. The common biotherapies for the treatment of psoriasis include monoclonal antibody against interleukin _IL-12_ and _IL-23_ (ustkeinumab) and anti-cytokine therapies (e.g., anti-tumor necrosis factor (_TNF_) therapies (adalimumab, etanercept, and infliximab)) [42]. Despite the progress in drug development, the approved drugs used to treat psoriasis have many limitations and defects. In spite of the strong anti-inflammatory effects of hormonal drugs (e.g., hydrocortisone acetate, prednisolone, betamethasone, and dexamethasone), external hormones are a temporary solution as long-term use may degrade the patients' own hormone secretion glands, and lead to the re-emergence or a serious recurrence of the disease. Anti-tumor necrosis factor (TNF) drugs are first-line therapies for patients who exhibit immune tolerance under conventional systemic therapy. Although these treatments are relatively effective, about 30-50% of the patients respond inadequately [8; 43]. Therefore, the development of new drugs to treat psoriasis has important research significance. A study has indicated that the medical genetics of drug targets may provide useful information with respect to drug repositioning, which involves predicting new activities and side effects of approved drugs [10]. This approach can accelerate the drug development process and reduce the associated risks. This paper mainly used the target-based approach to relocate a selection of approved drugs. Analyzing the immune mechanisms and susceptibility genes of psoriasis not only deepens our understanding of the pathology, but also facilitates the use these susceptible genes as drug targets. The gain of function (GOF) and loss of function (LOF) mutations of pathogenic genes are the two major mechanisms that lead to the development of diseases. Therefore, drugs with appropriate modes of action (MoA) should be selected to treat the diseases i.e., inhibitors/antagonists should be used to combat GOF-induced diseases, whereas activators/agonists should be used to treat LOF-induced diseases [44]. We collected information on approved drugs that are used to treat psoriasis from the DrugBank ([[http://www.drugbank.ca](http://www.drugbank.ca)]([http://www.drugbank.ca](http://www.drugbank.ca))), TTD ([[http://bidd.nus.edu.sg/BIDD-Databases/TTD/TTD.asp](http://bidd.nus.edu.sg/BIDD-Databases/TTD/TTD.asp)]([http://bidd.nus.edu.sg/BIDD-Databases/TTD/TTD.asp](http://bidd.nus.edu.sg/BIDD-Databases/TTD/TTD.asp))), and Clinical Trials ([[https://www.clinicaltrials.gov](https://www.clinicaltrials.gov)]([https://www.clinicaltrials.gov](https://www.clinicaltrials.gov))) websites. Furthermore, information regarding the GOF/LOF of pathogenic genes and the interactions between drugs and targets was collected from the OUGene website ([[http://www.csbio.sjtu.edu.cn](http://www.csbio.sjtu.edu.cn)]([http://www.csbio.sjtu.edu.cn](http://www.csbio.sjtu.edu.cn))). Using this method to reverse analyze, we found that many of these drugs met the requirements of the aforementioned pharmacological mechanisms (Table 2), thereby demonstrating the reliability of this strategy for fast and effective drug discovery. Additionally, we also selected a number of important genes from the list of pathogenic genes mentioned above as drug repositioning targets by querying the literature. Studies have shown that _STAT3_ is the most common and easily activated STAT family member in human malignancies.