Aubry Arthur, Galiacy Stéphane, Allouche Michèle
Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada.
Cancers (Basel). 2019 Feb 26;11(3):275. doi: 10.3390/cancers11030275.
ALK is a receptor tyrosine kinase, associated with many tumor types as diverse as anaplastic large cell lymphomas, inflammatory myofibroblastic tumors, breast and renal cell carcinomas, non-small cell lung cancer, neuroblastomas, and more. This makes ALK an attractive target for cancer therapy. Since ALK⁻driven tumors are dependent for their proliferation on the constitutively activated ALK kinase, a number of tyrosine kinase inhibitors have been developed to block tumor growth. While some inhibitors are under investigation in clinical trials, others are now approved for treatment, notably in ALK-positive lung cancer. Their efficacy is remarkable, however limited in time, as the tumors escape and become resistant to the treatment through different mechanisms. Hence, there is a pressing need to target ALK-dependent tumors by other therapeutic strategies, and possibly use them in combination with kinase inhibitors. In this review we will focus on the therapeutic potential of proapoptotic ALK-derived peptides based on the dependence receptor properties of ALK. We will also try to make a non-exhaustive list of several alternative treatments targeting ALK-dependent and independent signaling pathways.
间变性淋巴瘤激酶（ALK）是一种受体酪氨酸激酶，与多种肿瘤类型相关，如间变性大细胞淋巴瘤、炎性肌纤维母细胞瘤、乳腺癌和肾细胞癌、非小细胞肺癌、神经母细胞瘤等等。这使得ALK成为癌症治疗中一个有吸引力的靶点。由于ALK驱动的肿瘤的增殖依赖于持续激活的ALK激酶，因此已经开发了多种酪氨酸激酶抑制剂来阻断肿瘤生长。虽然一些抑制剂正在临床试验中进行研究，但其他一些抑制剂现已获批用于治疗，特别是在ALK阳性肺癌中。它们的疗效显著，但时间有限，因为肿瘤会通过不同机制逃脱并对治疗产生耐药性。因此，迫切需要通过其他治疗策略靶向ALK依赖性肿瘤，并可能将它们与激酶抑制剂联合使用。在这篇综述中，我们将基于ALK的依赖受体特性，重点探讨促凋亡的ALK衍生肽的治疗潜力。我们还将尝试列出针对ALK依赖性和非依赖性信号通路的几种替代治疗方法，但并不详尽。
