McCauley Carter, Anang Vasthy, Cole Breanna, Simmons Glenn E
University of Minnesota Medical School, Duluth, MN, MN 55812, USA.
Clinical and Translational Science Institute PREP Program, University of Minnesota Medical School, Minneapolis, MN, MN 55812, USA.
Med Res Arch. 2020 Oct;8(10). doi: 10.18103/mra.v8i10.2273. Epub 2020 Oct 29.
According to the National Institutes of Health, clear cell renal cell carcinoma (ccRCC) is the most common type of Renal Cell Carcinoma (RCC), making up approximately 75% of total renal carcinoma cases. Clear cell Renal Cell Carcinoma is characterized by a significant accumulation of lipids in the cytoplasm, which allows light from microscopes to pass through giving them a "clear" phenotype. Many of these lipids are in the form of fatty acids, both free and incorporated into lipid droplets. RCC is typically associated with a poor prognosis due to the lack of specific symptoms. Some symptoms include blood in urine, fever, lump on the side, weight loss, fatigue, to name a few; all of which can be associated with non-specific, non-cancerous, health conditions that contribute to difficult diagnosis. Treatment of RCC has typically been centered around radical nephrectomy as the standard of care, but due to the potentially small size of lesions and the possibility of causing surgically induced chronic kidney disease, treatments have shifted to more cautious, less invasive approaches. These approaches include active surveillance, nephron-sparing surgery, and other minimally invasive techniques like cryotherapy and renal ablation. Although these techniques have had the desired effect of reducing the number of surgeries, there is still considerable potential for renal impairment and the chance that tumors can grow out of control without surgery. With the difficulty that surrounds the treatment of ccRCC and its considerably high mortality rate amongst urological cancers, it is important to look for novel approaches to improve patient outcomes. This review looks at available literature and our data that suggests the lipogenic enzyme stearoyl-CoA desaturase may be more beneficial to patient survival than once thought. As our understanding of the importance of lipids in cell metabolism and longevity matures, it is important to present new perspectives that present a new understanding of ccRCC and the role of lipids in survival mechanisms engaged by transformed cells during cancer progression. In this review, we provide evidence that pharmacological inhibition of lipid desaturation in renal cancer patients is not without risk, and that the presence of unsaturated fatty acids may be a beneficial factor in patient outcomes. Although more direct experimental evidence is needed to make definitive conclusions, it is clear that the work reviewed herein should challenge our current understanding of cancer biology and may inform novel approaches to the diagnosis and treatment of ccRCC.
根据美国国立卫生研究院的数据，透明细胞肾细胞癌（ccRCC）是肾细胞癌（RCC）最常见的类型，约占肾癌病例总数的75%。透明细胞肾细胞癌的特征是细胞质中大量积累脂质，这使得显微镜下的光线能够穿过，赋予它们一种“透明”的表型。这些脂质中的许多以脂肪酸的形式存在，既有游离的，也有并入脂滴中的。由于缺乏特异性症状，RCC通常预后较差。一些症状包括血尿、发热、侧腹肿块、体重减轻、疲劳等等；所有这些都可能与非特异性、非癌性的健康状况有关，从而导致诊断困难。RCC的治疗通常以根治性肾切除术作为标准治疗方法，但由于病变可能较小，且有可能导致手术诱发的慢性肾病，治疗方法已转向更谨慎、侵入性更小的方法。这些方法包括主动监测、保留肾单位手术以及其他微创技术，如冷冻疗法和肾消融术。尽管这些技术达到了减少手术数量的预期效果，但仍有相当大的肾功能损害可能性，而且肿瘤在不进行手术的情况下可能会失控生长。鉴于围绕ccRCC治疗的困难以及其在泌尿系统癌症中相当高的死亡率，寻找新的方法来改善患者预后很重要。本综述研究了现有文献和我们的数据，这些数据表明生脂酶硬脂酰辅酶A去饱和酶对患者生存可能比以前认为的更有益。随着我们对脂质在细胞代谢和寿命中的重要性的理解逐渐成熟，提出新观点很重要，这些新观点能让我们对ccRCC以及脂质在癌症进展过程中转化细胞所采用的生存机制中的作用有新的认识。在本综述中，我们提供证据表明，对肾癌患者进行脂质去饱和的药物抑制并非没有风险，不饱和脂肪酸的存在可能是影响患者预后的一个有益因素。尽管需要更多直接的实验证据才能得出明确结论，但很明显，本文所综述的工作应该会挑战我们目前对癌症生物学的理解，并可能为ccRCC的诊断和治疗提供新方法。
