Challenging resistance mechanisms to therapies for metastatic melanoma

Aloe-emodin exerts a potent anticancer and immunomodulatory activity on BRAF-mutated human melanoma cells

“…Although DAB is effective as a single-agent treatment, resistance appears in most patients that thereafter have a poor clinical outcome. For this reason it has been suggested that combination therapy might expand the efficacy of targeted drugs (Tentori et al, 2013). In this work we demonstrated that treatment with AE potentiate the effects of DAB on human melanoma cells and melanospheres.…”

A new water soluble MAPK activator exerts antitumor activity in melanoma cells resistant to the BRAF inhibitor vemurafenib

“…In addition, about 50% of melanoma patients, whose disease harbors specific BRAF mutations (e.g., V600E, V600K), benefit from treatment with vemurafenib or dabrafenib, with or without the MEK inhibitor trametinib [2]. However, metastatic melanoma may easily develop resistance mechanisms evading the immune system control or accumulating genetic mutations with activation of alternative proliferation pathways.…”

Activating mutations of the oncogene EZH2 in cutaneous melanoma revealed by next generation sequencing

“…For patients with metastatic disease, the prognosis is very poor with median survival of 6-9 months [2]. Therapeutic options for patients with stage III and IV disease remain limited; however, advances in targeted therapy appear promising.…”

“…Therapeutic options for patients with stage III and IV disease remain limited; however, advances in targeted therapy appear promising. For example, approximately 50% of cutaneous melanomas contain an activating missense mutation in BRAF at valine 600 [2]. While many patients initially respond well to BRAF inhibitors, the response is not durable due to tumor resistance [2][3][4].…”

“…For example, approximately 50% of cutaneous melanomas contain an activating missense mutation in BRAF at valine 600 [2]. While many patients initially respond well to BRAF inhibitors, the response is not durable due to tumor resistance [2][3][4]. Targeting of the receptor tyrosine kinase KIT has shown mixed results [5].…”