Beatson Institute for Cancer Research, Glasgow, UK.
EMBO Rep. 2012 Oct;13(10):900-8. doi: 10.1038/embor.2012.127. Epub 2012 Sep 11.
The Rho-associated (ROCK) serine/threonine kinases have emerged as central regulators of the actomyosin cytoskeleton, their main purpose being to promote contractile force generation. Aided by the discovery of effective inhibitors such as Y27632, their roles in cancer have been extensively explored with particular attention focused on motility, invasion and metastasis. Recent studies have revealed a surprisingly diverse range of functions of ROCK. These insights could change the way ROCK inhibitors might be used in cancer therapy to include the targeting of stromal rather than tumour cells, the concomitant blocking of ROCK and proteasome activity in K-Ras-driven lung cancers and the combination of ROCK with tyrosine kinase inhibitors for treating haematological malignancies such as chronic myeloid leukaemia. Despite initial optimism for therapeutic efficacy of ROCK inhibition for cancer treatment, no compounds have progressed into standard therapy so far. However, by carefully defining the key cancer types and expanding the appreciation of ROCK's role in cancer beyond being a cell-autonomous promoter of tumour cell invasion and metastasis, the early promise of ROCK inhibitors for cancer therapy might still be realized.
Rho 相关（ROCK）丝氨酸/苏氨酸激酶已成为肌动球蛋白细胞骨架的核心调节剂，其主要目的是促进收缩力的产生。在发现有效的抑制剂（如 Y27632）的帮助下，它们在癌症中的作用得到了广泛的研究，特别关注于运动性、侵袭性和转移性。最近的研究揭示了 ROCK 令人惊讶的多种功能。这些新的见解可能会改变 ROCK 抑制剂在癌症治疗中的应用方式，包括靶向基质细胞而不是肿瘤细胞，同时阻断 ROCK 和蛋白酶体在 K-Ras 驱动的肺癌中的活性，以及将 ROCK 与酪氨酸激酶抑制剂联合用于治疗血液恶性肿瘤，如慢性髓性白血病。尽管最初对 ROCK 抑制治疗癌症的疗效持乐观态度，但迄今为止没有一种化合物能进展到标准治疗。然而，通过仔细定义关键的癌症类型，并扩大对 ROCK 在癌症中的作用的认识，超越其作为肿瘤细胞侵袭和转移的自主促进因子，ROCK 抑制剂治疗癌症的早期前景仍有可能实现。
