Targeting RAS in pediatric cancer: is it becoming a reality?
Targeting RAS in pediatric cancer: is it becoming a reality?
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DOI：
10.1097/mop.0000000000000856
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发表时间：
2020-02
影响因子：
3.6
通讯作者：
Yohe, Marielle E.
中科院分区：
文献类型：
--
作者：
Vaseva, Angelina V.;Yohe, Marielle E.
目前的审查旨在突出RAS突变在儿科白血病和实体瘤的频率，并提出针对儿科癌症的致癌RAS的策略。三种RAS基因（HRAS、NRAS和KRAS）构成人类癌症中最常突变的癌基因家族。RAS突变通常在美国癌症死亡的三个主要原因中观察到，即肺癌，胰腺癌和结直肠癌。RAS突变与这些侵袭性恶性肿瘤的关联激发了NCI RAS倡议的创建，并刺激了大力开发抑制致癌RAS的策略，最近取得了很大成功。RAS突变经常在儿科癌症中观察到;然而，抗RAS药物开发的最新进展尚未转化为儿科临床试验。我们发现RAS在常见和罕见的儿科恶性肿瘤中发生突变，并且致癌RAS在这些癌症中具有功能依赖性。针对主要影响成人的恶性肿瘤正在寻求许多靶向RAS的策略，并且在这些药物的临床试验中明确需要纳入儿科患者。
The current review aims to highlight the frequency of RAS mutations in pediatric leukemias and solid tumors and to propose strategies for targeting oncogenic RAS in pediatric cancers. The three RAS genes (HRAS, NRAS, and KRAS) comprise the most frequently mutated oncogene family in human cancer. RAS mutations are commonly observed in three of the leading causes of cancer death in the US, namely lung cancer, pancreatic cancer, and colorectal cancer. The association of RAS mutations with these aggressive malignancies inspired the creation of the NCI RAS initiative and spurred intense efforts to develop strategies to inhibit oncogenic RAS, with much recent success. RAS mutations are frequently observed in pediatric cancers; however, recent advances in anti-RAS drug development have yet to translate into pediatric clinical trials. We find that RAS is mutated in common and rare pediatric malignancies and that oncogenic RAS confers a functional dependency in these cancers. Many strategies for targeting RAS are being pursued for malignancies that primarily affect adults and there is a clear need for inclusion of pediatric patients in clinical trials of these agents.