Metastatic melanoma after solid organ transplantation: An interdisciplinary, institution-based review of management with systemic and targeted therapies

Tripathi, Shivani; Morris, Caroline; Alhamad, Tarek; Fields, Ryan C.; Linette, Gerald P.; Cornelius, Lynn A.

doi:10.1016/j.jaad.2017.06.031

Cited by 4 publications

(1 citation statement)

References 6 publications

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“…On the one hand, melanoma patients with pre-existing autoimmune diseases who receive ipilimumab treatment present frequent disease flares and exacerbations, requiring additional immunosuppression or therapy discontinuation [6,7]. On the other hand, solid organ transplant recipients are at increased risk of developing metastatic melanoma, and when they do, they exhibit a higher probability for graft rejection upon immune checkpoint inhibitor treatment [8,9]. In general, a dysregulated immune system poses as the Sword of Damocles in the decision of clinicians to prescribe immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

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

Logotheti

Pützer

2019

Cancers

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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.

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