The genetic basis of kidney cancer: a metabolic disease

By W. Marston Linehan, R. Srinivasan, Laura S. Schmidt. Nature reviews. Urology, 2010

720 citations recorded by the source corpus.

Kidney cancer is not a single disease but comprises a number of different types of cancer that occur in the kidney, each caused by a different gene with a different histology and clinical course that responds differently to therapy. Each of the seven known kidney cancer genes, VHL, MET, FLCN, TSC1, TSC2, FH and SDH, is involved in pathways that respond to metabolic stress or nutrient stimulation. The VHL protein is a component of the oxygen and iron sensing pathway that regulates hypoxia-inducible factor (HIF) levels in the cell. HGF–MET signaling affects the LKB1–AMPK energy sensing cascade. The FLCN–FNIP1–FNIP2 complex binds AMPK and, therefore, might interact with the cellular energy and nutrient sensing pathways AMPK–TSC1/2–mTOR and PI3K–Akt–mTOR. TSC1–TSC2 is downstream of AMPK and negatively regulates mTOR in response to cellular energy deficit. FH and SDH have a central role in the mitochondrial tricarboxylic acid cycle, which is coupled to energy production through oxidative phosphorylation. Mutations in each of these kidney cancer genes result in dysregulation of metabolic pathways involved in oxygen, iron, energy or nutrient sensing, suggesting that kidney cancer is a disease of cell metabolism. Targeting the fundamental metabolic abnormalities in kidney cancer provides a unique opportunity for the development of more-effective forms of therapy for this disease.

Subfields: Cancer Research, Genetics, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/57e37e4b98ae7507057910975b7f6b19a0252d1b

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. W. Marston Linehan
2. Christopher Sander
3. Chad Creighton
4. R. Srinivasan
5. E. Gibb

In Genetics

1. Hui Shen
2. Christopher Sander
3. Richard A. Gibbs
4. Ronglai Shen

In Pulmonary and Respiratory Medicine

1. Christopher Corless
2. M. Heinrich

Citations in the corpus

• Gastrointestinal stromal tumours: origin and molecular oncology (2011, background): “Similar mechanisms have been shown in some types of renal cell carcinoma (through the loss of fumarate hydratase”
• COMPREHENSIVE MOLECULAR CHARACTERIZATION OF CLEAR CELL RENAL CELL CARCINOMA (2013, background): “Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways.”
• An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma (2016, positive): “Cancer metabolism has recently attracted renewed interest, in part due to the identification of tumorigenic mutations in the metabolic genes IDH1, IDH2, FH, and SDHB (Kaelin and McKnight, 2013; Linehan et al., 2010).”
• The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma (2018, methodology): “Our understanding of RCC has evolved over the past 40 years, from considering RCC as a single entity to our current understanding that RCC is made up of many different subtypes of renal cancer, each with different histology, distinctive genetic and molecular alterations, different clinical courses, ”