11/7/2022 0 Comments Pdf plus in cell![]() ![]() Thus, it is important to find alternative melanoma treatment options, targeting biological processes that are different from current therapies. Although promising, immunotherapies are not without caveats-not all patients respond and some patients relapse 2, 3, 4. Targeted therapies work only on a subset of patients with specific mutations however, of patients that initially respond, almost all relapse. Treatment of advanced melanoma has dramatically improved in recent years, and currently include targeted therapies against BRAF or MEK, and immunotherapy. The incidence of invasive melanoma cases has increased by 54% in the last decade 1. Taken together, this study suggests that dual targeting of MCL1 and BCLXL should be considered as a treatment option for difficult-to-treat melanoma patients. ![]() In vitro, the combined inhibition of MCL1 and BCLXL resulted in significantly effective cell killing compared to single-agent treatment ( pāā0.40). We used cell lines derived from patients with difficult-to-treat melanomas. These include clinical-trial-ready compounds such as ABT-263 (Navitoclax) and S63845/S64315 (MIK655). We then examined the effects of combining BH3 mimetics to target MCL1 and BCLXL in vitro and in vivo. We used genetic knockdown and pharmacologic approaches of BH3 mimetics to target anti-apoptotic BCL2 family members and identified MCL1 and BCLXL as crucial pro-survival members in melanoma. One of most appealing is targeting the apoptotic/anti-apoptotic system that is effective against leukemia. ![]() Therefore, it is necessary to understand and explore other biological processes that may provide new therapeutic approaches. These melanomas include those without the genetic markers for targeted therapy, non-responsive to immunotherapy, and those who have relapsed or exhausted their therapeutic options. However, a subset of melanomas are difficult-to-treat. Current treatment for patients with metastatic melanoma include molecular-targeted therapies and immune checkpoint inhibitors. ![]()
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