The Heterogeneity Metabolism of Renal Cell Carcinomas

Abstract

According to data from the American Cancer Society, cancer is one of the deadliest health problems globally. Annually, renal cell carcinoma (RCC) causes more than 100,000 deaths worldwide [1–4], posing an urgent need to develop effective treatments to increase patient survival outcomes. New therapies are expected to address a major factor contributing to cancer’s resistance to standard therapies: oncogenic heterogeneity. Gene expression can vary tremendously among different types of cancers, different patients of the same tumor type, and even within individual tumors; various metabolic phenotypes can emerge, making singletherapy approaches insufficient. Novel strategies targeting the diverse metabolism of cancers aim to overcome this obstacle. Though some have yielded positive results, it remains a challenge to uncover all of the distinct metabolic profiles of RCC. In the quest to overcome this obstacle, the metabolic oriented research focusing on these cancers has offered freshly new perspectives, which are expected to contribute heavily to the development of new treatments.

Glucose Metabolism in Cancer: The Warburg Effect and Beyond

“…Examination of different tumor types revealed that the balance between aerobic glycolysis and oxidative phosphorylation could be very different. In a study evaluating the variability of metabolic gene expression across multiple different tumor types, it was found that there was an upregulation of genes related to oxidative phosphorylation in ovarian, lymphoma [27], leukemia, and lung cancers, whereas the opposite was true in thyroid, colon, pancreatic [28], and renal cancers [29,30]. It is thought that the variable activation of different oncogenes such as RAS, AKT, and c-MYC is the driver behind these differences [31][32][33][34][35].…”

Altered Plasma, Urine, and Tissue Profiles of Sulfatides and Sphingomyelins in Patients with Renal Cell Carcinoma

“…It was reported that SM accumulate in the HCT-116 (human colon cancer cell lines) during apoptosis [44]. Hence, their overall downregulation might be related to the regulation of cancer cell survival [45].…”

Glutamine Metabolism in Cancer

“…A study by Gameiro et al found that the transcription factor HIF expression maintained a low level of intracellular citrate to maintain adequate lipogenesis. Therefore, the von Hippel-Lindau (VHL)deficient RCC cells that constitutively express HIF-1α and/or HIF-2α become heavily dependent on glutamine for proliferation [26,27].…”