PDF(Pubmed)
Abstract：
Pituitary tumors (PT) are mostly benign, although occasionally they demonstrate aggressive behavior, invasion of surrounding tissues, rapid growth, resistance to conventional treatments, and multiple recurrences. The pathogenesis of PT is still not fully understood, and the factors responsible for its invasiveness, aggressiveness, and potential for metastasis are unknown. RAF/MEK/ERK and mTOR signaling are significant pathways in the regulation of cell growth, proliferation, and survival, its importance in tumorigenesis has been highlighted. The aim of our review is to determine the role of the activation of PI3K/AKT/mTOR and RAF/MEK/ERK pathways in the pathogenesis of pituitary tumors. Additionally, we evaluate their potential in a new therapeutic approach to provide alternative therapies and improved outcomes for patients with aggressive pituitary tumors that do not respond to standard treatment. We perform a systematic literature search using the PubMed, Embase, and Scopus databases (search date was 2012-2023). Out of the 529 screened studies, 13 met the inclusion criteria, 7 related to the PI3K/AKT/mTOR pathway, and 7 to the RAF/MEK/ERK pathway (one study was used in both analyses). Understanding the specific factors involved in PT tumorigenesis provides opportunities for targeted therapies. We also review the possible new targeted therapies and the use of mTOR inhibitors and TKI in PT management. Although the RAF/MEK/ERK and PI3K/AKT/mTOR pathways play a pivotal role in the complex signaling network along with many interactions, further research is urgently needed to clarify the exact functions and the underlying mechanisms of these signaling pathways in the pathogenesis of pituitary adenomas and their role in its invasiveness and aggressive clinical outcome.
摘要：
垂体肿瘤（PT）大多是良性的，尽管他们偶尔会表现出攻击性行为，侵入周围组织，快速增长,对常规治疗的抵抗力，和多次复发。PT的发病机制仍未完全了解,以及造成其侵袭性的因素，侵略性,和转移的可能性是未知的。RAF/MEK/ERK和mTOR信号是调节细胞生长的重要通路，扩散,和生存，它在肿瘤发生中的重要性已被强调。我们综述的目的是确定PI3K/AKT/mTOR和RAF/MEK/ERK通路的激活在垂体瘤发病机制中的作用。此外,我们评估了他们在新的治疗方法中的潜力,为对标准治疗无反应的侵袭性垂体瘤患者提供替代疗法和改善结局.我们使用PubMed进行系统的文献检索，Embase,和Scopus数据库（搜索日期为2012-2023年）。在529项筛选研究中，13符合纳入标准，7与PI3K/AKT/mTOR通路有关，和7到RAF/MEK/ERK途径（两项分析均使用一项研究）。了解PT肿瘤发生中涉及的特定因素为靶向治疗提供了机会。我们还回顾了可能的新的靶向治疗以及mTOR抑制剂和TKI在PT管理中的使用。尽管RAF/MEK/ERK和PI3K/AKT/mTOR通路在复杂的信号传导网络中发挥着关键作用以及许多相互作用，迫切需要进一步的研究来阐明这些信号通路在垂体腺瘤发病机制中的确切功能和潜在机制,以及它们在垂体腺瘤侵袭性和侵袭性临床结局中的作用.
