从肿瘤到骨骼:生长因子受体在癌症转移中扮演关键角色
From Tumor to Bone: Growth Factor Receptors as Key Players in Cancer Metastasis.
作者信息
Mohammad Khalid Said, Akhund Shahid Akhtar
机构信息
Department of Anatomy, College of Medicine, Alfaisal University, 1153 Riyadh, Saudi Arabia.
出版信息
Front Biosci (Landmark Ed). 2024 May 13;29(5):184. doi: 10.31083/j.fbl2905184.
This review article explores the intricate correlation between growth factors and bone metastases, which play a crucial role in the development of several types of malignancies, namely breast, prostate, lung, and renal cancers. The focal point of our discussion is on crucial receptors for growth factors, including Epidermal Growth Factor Receptor (EGFR), Transforming Growth Factor-β (TGFβ), Vascular Endothelial Growth Factor Receptor (VEGFR), and Fibroblast Growth Factor Receptor (FGFR). These receptors, which are essential for cellular activities including growth, differentiation, and survival, have important involvement in the spread of cancer and the interactions between tumors and the bone environment. We discuss the underlying mechanisms of bone metastases, with a specific emphasis on the interaction between growth factor receptors and the bone microenvironment. EGFR signaling specifically enhances the process of osteoclast development and the formation of osteolytic lesions, especially in breast and lung malignancies. TGFβ receptors have a role in both osteolytic and osteoblastic metastases by releasing TGFβ, which attracts cancer cells and promotes bone remodeling. This is a crucial element in the spread of prostate cancer to the bones. The functions of FGFR and VEGFR in the processes of bone formation and tumor angiogenesis, respectively, highlight the complex and diverse nature of these interactions. The review emphasizes the possibility of targeted therapeutics targeting these receptors to interrupt the cycle of tumor development and bone degradation. Therapeutic approaches include focusing on the VEGF/VEGFR, EGF/EGFR, FGF/FGFR, and TGFβ/TGFβR pathways. These include a variety of compounds, such as small molecule inhibitors and monoclonal antibodies, which have shown potential to interfere with tumor-induced alterations in bone. The text discusses clinical trials and preclinical models, offering insights into the effectiveness and constraints of various treatments. Ultimately, this study provides a succinct but thorough summary of the present knowledge and treatment strategies focused on growth factor receptors in bone metastases. This highlights the significance of comprehending the signaling of growth factor receptors in the microenvironment where tumors spread to the bones, as well as the possibility of using targeted therapies to enhance the results for cancer patients with bone metastases. The advancement of treating bone metastases hinges on the development of treatments that specifically target the intricate relationships between malignancies and bone.
这篇综述文章探讨了生长因子与骨转移之间的复杂关联,生长因子在几种类型的恶性肿瘤(即乳腺癌、前列腺癌、肺癌和肾癌)的发展中起着关键作用。我们讨论的重点是生长因子的关键受体,包括表皮生长因子受体(EGFR)、转化生长因子-β(TGFβ)、血管内皮生长因子受体(VEGFR)和成纤维细胞生长因子受体(FGFR)。这些受体对包括生长、分化和存活在内的细胞活动至关重要,在癌症扩散以及肿瘤与骨环境之间的相互作用中具有重要作用。我们讨论了骨转移的潜在机制,特别强调了生长因子受体与骨微环境之间的相互作用。EGFR信号传导特别增强破骨细胞发育过程和成骨溶解病变的形成,尤其是在乳腺癌和肺癌中。TGFβ受体通过释放TGFβ在溶骨性和成骨性转移中均起作用,TGFβ吸引癌细胞并促进骨重塑。这是前列腺癌扩散至骨骼过程中的关键因素。FGFR和VEGFR分别在骨形成和肿瘤血管生成过程中的功能,突出了这些相互作用的复杂和多样性质。该综述强调了靶向这些受体的靶向治疗以中断肿瘤发展和骨降解循环的可能性。治疗方法包括关注VEGF/VEGFR、EGF/EGFR、FGF/FGFR和TGFβ/TGFβR途径。这些包括多种化合物,如小分子抑制剂和单克隆抗体,它们已显示出干扰肿瘤诱导的骨改变的潜力。本文讨论了临床试验和临床前模型,深入了解了各种治疗方法的有效性和局限性。最终,本研究对目前关于骨转移中生长因子受体的知识和治疗策略进行了简洁而全面的总结。这突出了理解肿瘤扩散至骨骼的微环境中生长因子受体信号传导的重要性,以及使用靶向治疗来改善骨转移癌症患者治疗效果的可能性。治疗骨转移的进展取决于开发专门针对恶性肿瘤与骨之间复杂关系的治疗方法。