Universitat de Lleida-IRBlLeida, Cell Calcium Signaling Lab, 25198, Rovira Roure, 80, Lleida, Spain.
Universitat de Lleida-IRBlLeida, Cell Calcium Signaling Lab, 25198, Rovira Roure, 80, Lleida, Spain.
Biochim Biophys Acta Rev Cancer. 2020 Apr;1873(2):188364. doi: 10.1016/j.bbcan.2020.188364. Epub 2020 Apr 7.
Hyperactivation of the Mitogen Activated Protein Kinase (MAPK) pathway is prevalent in melanoma, principally due to mutations in the BRAF and NRAS genes. MAPK inhibitors are effective only short-term, and recurrence occurs due to functional redundancies or intertwined pathways. The remodeling of Ca signaling is also common in melanoma cells, partly through the increased expression of T-type channels (TTCCs). Here we summarize current knowledge about the prognostic value and molecular targeting of TTCCs. Furthermore, we discuss recent evidence pointing to TTCCs as molecular switches for melanoma chemoresistance, which set the grounds for novel combined therapies against the advanced disease.
丝裂原活化蛋白激酶（MAPK）通路的过度激活在黑色素瘤中很常见，主要是由于 BRAF 和 NRAS 基因的突变。MAPK 抑制剂仅在短期内有效，并且由于功能冗余或交织的途径而复发。钙信号的重塑在黑色素瘤细胞中也很常见，部分是通过增加 T 型通道（TTCCs）的表达。在这里，我们总结了 TTCCs 的预后价值和分子靶向的最新知识。此外，我们还讨论了最近的证据，表明 TTCCs 是黑色素瘤化疗耐药性的分子开关，为针对晚期疾病的新型联合治疗奠定了基础。
