Targeting the molecules useful for the diagnosis and treatment of endometrial cancers

子宫内膜癌是第二常见的妇科恶性肿瘤，其发病率在过去十年中在日本急剧增加。虽然子宫内膜癌的手术和化疗治疗已经很成熟，但对分子靶向治疗的需求已经增加，特别是对于复发性和/或放射性或化学抗性疾病。因此，有必要更好地了解子宫内膜致癌物的分子途径。最常见的遗传异常是PTEN和ERAS的突变。PTEN突变和ERAS突变分别激活PI 3 K途径和ERK-MAP途径。在本研究中，使用临床样本，有没有KRAS或BRAF和p-ERK 1/2表达之间的显着关联。低表达的患者预后良好。因此，在子宫内膜癌中，ERK 1/2的激活以ERAS和BRAF I依赖的方式发生。在大约60%的子宫内膜癌中观察到高水平的p-AKT表达。它独立于PTEN突变和PIK 3CA突变两者发生。此外，p-AKT表达与潜在的下游靶标如p-mTOR和/或pTORO 1/3a的表达不相关。p-AKT的高表达与ERK密切相关。目前的研究揭示了复杂的信号通路的存在比传统的致癌途径。子宫内膜癌的分子靶向诊断和治疗是一条漫长的道路。

Endometrial cancer is the second most common gynecological malignancy and its incidence has increased dramatically over the last decade in Japan. Although the surgical and chemotherapeutic treatments for endometrial cancers are well-established, the need for molecular-target therapy has increased, especially for recurrent and/or radio- or chemo-resistant diseases. Thus there is a need for a better understanding of the molecular pathway of endometrial carcinogens.The most frequent genetic abnormalities are mutations in PTEN and ERAS. A PTEN mutation and ERAS mutation activates the PI3K pathway and ERK - MAP pathway, respectively. In the present study using the clinical samples, there is no significant association between KRAS or BRAF and p-ERK1/2 expression. Patients with low expression have a favorable prognosis. Thus, the activation of ERK1/2 occurs in a ERAS and BRAF I dependent manner in endometrial cancer. A High level of p-AKT expression was observed in approximately 60% of endometrial cancers. It occurs independently of both PTEN mutations and PIK3CA mutations. Furthermore, p-AKT expression did not correlated with expression of potential downstream targets such as p-mTOR and/or p TORO 1/3a. The high-expression of p-AKT was strongly associated with ERK. The present study revealed the presence of complex signaling pathways other than the conventional carcinogenic pathway. The molecular targeting for the diagnosis and treatment of endometrial cancers is a long way for the success.