The metabolic basis of kidney cancer

Abstract

Kidney cancer is not a single disease; it is made up of a number of different types of cancer that occur in the kidney. Each of these different types of kidney cancer can have a different histology, have a different clinical course, can respond differently to therapy and is caused by a different gene. Kidney cancer is essentially a metabolic disease; each of the known genes for kidney cancer, VHL, MET, FLCN, TSC1, TSC2, TFE3, TFEB, MITF, fumarate hydratase (FH), succinate dehydrogenase B (SDHB), succinate dehydrogenase D (SDHD), and PTEN genes is involved in the cells ability to sense oxygen, iron, nutrients or energy. Understanding the metabolic basis of kidney cancer will hopefully provide the foundation for the development of effective forms of therapy for this disease.

Figure 1

Kidney cancer is not a single disease; it is made up of a number of different and specific types of cancers that can occur within the kidney. Each of these different types of kidney cancer can be characterized by differing histologies, different clinical courses, differing responses to a number of varied therapies and association with alterations to different genes. (TBD*: to be determined.)

Figure 2

Patients affected with von Hippel-Lindau are at risk for the development of bilateral, multifocal (A,B) clear cell kidney cancer (C) and have germline mutation of the VHL gene (D). From Linehan, et al.(1)

Figure 3

Patients affected with Hereditary Papillary Renal Carcinoma (HPRC) at risk for the development of bilateral, multifocal (A,B) type 1 papillary kidney cancer. HPRC is a highly penetrant autosomal dominant hereditary cancer syndrome (D). From Linehan, et al.(1)

Figure 4

Patients affected with Birt-Hogg-Dubé (BHD) are at risk for the development if bilateral, multifocal kidney cancer (left upper and left lower panels) with chromophobe (upper right panel), hybrid oncocytic (right middle panel) and oncocytoma (right lower panel). From Linehan, et al.(1)

Figure 5

BHD is a highly penetrant autosomal dominant hereditary cancer syndrome characterized by germline mutation of the FLCN gene. From Toro, et al. (81).

Figure 6

Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) is an autosomal dominant hereditary cancer syndrome (right lower panel) in which affected individuals are at risk for the development cutaneous and uterine leiomyomas (upper middle and upper right panels) and an aggressive form of kidney cancer (upper left panel). HLRCC is characterized by germline mutation of the Krebs cycle enzyme gene, fumarate hydratase. From Linehan, et al.(1)

Figure 7

Kidney cancer is essentially a metabolic disease. Each of the genes known to be associated with the development of kidney cancer, VHL, MET, FLCN, FH, SDHB, SDHD, TSC2, TSC1, TFE3, TFEB, MITF and PTEN, is involved in the cell's ability to sense oxygen, iron, nutrients or energy. Adapted from Linehan, et al. (2)