STAT3 and STAT5 Targeting for Simultaneous Management of Melanoma and Autoimmune Diseases

• Published in: Cancers Vol. 11; no. 10; p. 1448
• Main Authors: Logotheti, Stella, Pützer, Brigitte M.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 27.09.2019; MDPI
• Subjects: Antigens; Antitumor activity; autoimmune disease; Autoimmune diseases; Cancer therapies; Complications; Deactivation; Immune response; Immune system; Immunotherapy; Inflammation; Inflammatory bowel disease; Medical prognosis; Melanoma; Metastases; Metastasis; Pancreatitis; Patients; Psoriasis; Quality of life; Review; Rheumatoid arthritis; Skin cancer; stat3; Stat3 protein; stat5; Stat5 protein; Tumors; tumor–immune cell interactions; Vitiligo
• DOI: 10.3390/cancers11101448
• ISSN: 2072-6694

Melanoma is a skin cancer which can become metastatic, drug-refractory, and lethal if managed late or inappropriately. An increasing number of melanoma patients exhibits autoimmune diseases, either as pre-existing conditions or as sequelae of immune-based anti-melanoma therapies, which complicate patient management and raise the need for more personalized treatments. STAT3 and/or STAT5 cascades are commonly activated during melanoma progression and mediate the metastatic effects of key oncogenic factors. Deactivation of these cascades enhances antitumor-immune responses, is efficient against metastatic melanoma in the preclinical setting and emerges as a promising targeting strategy, especially for patients resistant to immunotherapies. In the light of the recent realization that cancer and autoimmune diseases share common mechanisms of immune dysregulation, we suggest that the systemic delivery of STAT3 or STAT5 inhibitors could simultaneously target both, melanoma and associated autoimmune diseases, thereby decreasing the overall disease burden and improving quality of life of this patient subpopulation. Herein, we review the recent advances of STAT3 and STAT5 targeting in melanoma, explore which autoimmune diseases are causatively linked to STAT3 and/or STAT5 signaling, and propose that these patients may particularly benefit from treatment with STAT3/STAT5 inhibitors.