Drug Repurposing at the Interface of Melanoma Immunotherapy and Autoimmune Disease

Abstract

Cancer cells have a remarkable ability to evade recognition and destruction by the immune system. At the same time, cancer has been associated with chronic inflammation, while certain autoimmune diseases predispose to the development of neoplasia. Although cancer immunotherapy has revolutionized antitumor treatment, immune-related toxicities and adverse events detract from the clinical utility of even the most advanced drugs, especially in patients with both, metastatic cancer and pre-existing autoimmune diseases. Here, the combination of multi-omics, data-driven computational approaches with the application of network concepts enables in-depth analyses of the dynamic links between cancer, autoimmune diseases, and drugs. In this review, we focus on molecular and epigenetic metastasis-related processes within cancer cells and the immune microenvironment. With melanoma as a model, we uncover vulnerabilities for drug development to control cancer progression and immune responses. Thereby, drug repurposing allows taking advantage of existing safety profiles and established pharmacokinetic properties of approved agents. These procedures promise faster access and optimal management for cancer treatment. Together, these approaches provide new disease-based and data-driven opportunities for the prediction and application of targeted and clinically used drugs at the interface of immune-mediated diseases and cancer towards next-generation immunotherapies.

Sunset Yellow protects against oxidative damage and exhibits chemoprevention in chemically induced skin cancer model

“…To understand the mode of action of SY as antioxidant, anti-genotoxic, and cytoprotective agents, we screened potential biological targets using computational pharmacophore screening methods. Structure-based pharmacophore virtual screening methods are successfully used in the past for target identification, off-target prediction, toxicity prediction, drug repositioning 42 – 48 . Through pharmacophore screening, several target proteins are identified, including fibroblast growth factor receptor 2 (FGFR2), epidermal growth factor receptor (EGFR), carbonic anhydrase 2 (CAH2), glycogen synthase kinase-3 beta (GSK3β), and Kelch-like ECH-associated protein 1 (KEAP1).…”

Efficacy of Pembrolizumab in Advanced Melanoma: A Narrative Review

“…Another interesting association is with pembrolizumab and metformin, which seems to be able to increase the efficacy of pembrolizumab by reducing CD8+ T-cell apoptosis, reducing intratumoral hypoxia and reducing PD-L1 expression, thus favoring a better antitumor cell response [73]. All this is an example of how drug repurposing can be a useful strategy to improve the efficacy of current treatments, especially in resistant cases.…”

Editorial: Anti-inflammatory drug development focusing on immune mediated diseases

“…Identification of new natural products, synthetic molecules, drug repurposing, in silico molecular modelling studies associated with chemical synthesis represent important strategies for the development of new drugs (Spitschak et al, 2022;Wainwright et al, 2022). The global demand for new drugs and the associated scientific challenges were motivations for this special edition, with the aim to bring together scientific research works that addressed the development of new immunomodulatory drugs.…”