Teisseire Manon, Giuliano Sandy, Pagès Gilles
University Cote d'Azur (UCA), Institute for Research on Cancer and Aging of Nice, CNRS UMR 7284; INSERM U1081, Centre Antoine Lacassagne, 06189 Nice, France.
Biomedicines. 2024 Feb 7;12(2):385. doi: 10.3390/biomedicines12020385.
This review explores treating metastatic clear cell renal cell carcinoma (ccRCC) through current therapeutic modalities-anti-angiogenic therapies and immunotherapies. While these approaches represent the forefront, their limitations and variable patient responses highlight the need to comprehend underlying resistance mechanisms. We specifically investigate the role of fibrosis, prevalent in chronic kidney disease, influencing tumour growth and treatment resistance. Our focus extends to unravelling the intricate interplay between fibrosis, immunotherapy resistance, and the tumour microenvironment for effective therapy development. The analysis centres on connective tissue growth factor (CTGF), revealing its multifaceted role in ccRCC-promoting fibrosis, angiogenesis, and cancer progression. We discuss the potential of targeting CTGF to address the problem of fibrosis in ccRCC. Emphasising the crucial relationship between fibrosis and the immune system in ccRCC, we propose that targeting CTGF holds promise for overcoming obstacles to cancer treatment. However, we recognise that an in-depth understanding of the mechanisms and potential limitations is imperative and, therefore, advocate for further research. This is an essential prerequisite for the successful integration of CTGF-targeted therapies into the clinical landscape.
本综述探讨了通过当前的治疗方式——抗血管生成疗法和免疫疗法来治疗转移性透明细胞肾细胞癌（ccRCC）。虽然这些方法代表了前沿进展，但其局限性以及患者反应的差异凸显了理解潜在耐药机制的必要性。我们特别研究了在慢性肾病中普遍存在的纤维化对肿瘤生长和治疗耐药性的影响。我们的重点还包括揭示纤维化、免疫治疗耐药性和肿瘤微环境之间复杂的相互作用，以开发有效的治疗方法。分析聚焦于结缔组织生长因子（CTGF），揭示了其在ccRCC中促进纤维化、血管生成和癌症进展的多方面作用。我们讨论了靶向CTGF解决ccRCC纤维化问题的潜力。强调纤维化与ccRCC免疫系统之间的关键关系，我们提出靶向CTGF有望克服癌症治疗中的障碍。然而，我们认识到深入了解其机制和潜在局限性至关重要，因此主张进一步研究。这是将CTGF靶向疗法成功整合到临床实践中的必要前提。
