Review: Warburg effect and renal cancer caused by errs in fumarate hydratase encoding gene

Abstract

The several types of heterogeneous kidney cancers are interrelated by their primary sites of pathology. Despite its origin in the kidney, renal cell carcinoma (RCC) is associated with its varying genetic basis. Von Hippel-Lindau (VHL) syndrome is the earliest and, thus the most highly, characterized of genetic forms of kidney cancer, which is associated with alterations in the Von Hippel-Lindau (VHL) gene. As a result of his studies and investigations, Otto Warburg reached the conclusion that cancer's fundamental cause is altered mechanism. But this theory was disdained because of the discovery of tumor suppressor genes and oncogenes. Lately, the breakthrough finding about the tumor suppressing role of gene coding for enzymes involved in Krebs cycle has revived the interest in Warburg's hypothesis. This effect has led to the uncovering of the links between metabolic alterations, mitochondrial dysfunction and cancer. One such metastatic cancer characterized by the germ-line inactivating mutation of the gene coding for fumarate hydratase (FH), a Krebs cycle's enzyme, is hereditary leiomyomatosis and renal cell carcinoma (HLRCC). In this review paper, we have discussed the background of this carcinoma, the metabolic dysfunction causing it and its therapeutic solutions.