The Study of the Mechanisms and Therapeutic Effects of Ssri Antidepressants on Melanoma

Malignant melanoma is the most lethal skin cancer, whereas the current treatment of choice remains with surgery, immunotherapy and target therapy. Although breakthroughs have been made, the multiple mutational processes and high metastasis is yet to be overcome, leaving the breakthrough of melanoma treatment in a dilemma. Combination of multiple medications is still not enough to well control the progression. Recent studies indicated that the cachexia and therapies side effects interfere with quality of life, decreased adherence to treatment regimes and even shorten survival. Cancer patients were subscribed for SSRI antidepressants to relieve the cancer-related distress, improved quality of life and increased completion rate of melanoma treatment in the clinical. Retrospective cohort studies indicated several antidepressants decreased the risk of glioma and colorectal cancer thus suggested the potential of adjuvant therapy in cancer. Our preliminary results have selected several SSRI antidepressants and have found paroxetine specifically block melanoma cell viability and abolished melanoma migration/invasion. Melanoma xenograft animal study also confirmed paroxetine decreased melanoma growth in vivo thus indicated the melanoma treatment potential in clinical. Our preliminary results suggest paroxetine blocked RAF-MEK-ERK signaling pathway and induced mitochondrial calcium overloaded thus suppressed melanoma proliferation and induced cell death. Therefore we hypothesize that significant breakthrough in treating and preventing the melanoma may be achieved via the combination of SSRI antidepressant and clinical target therapies. Our study aims to understand more regarding the toxicity and mechanism of action in combination of SSRI antidepressants and target therapy medications. Objectives of this three-year research project are as follow: First year: the evaluation and selection of the drug efficacy via National health insurance research database analysis and in vitro study. Second year: the evaluation of drug efficacy and its mechanism. Third year: animal studies and pre-clinical study evaluation.