Send to

Choose Destination
Semin Cancer Biol. 2019 Nov 2. pii: S1044-579X(19)30271-8. doi: 10.1016/j.semcancer.2019.10.016. [Epub ahead of print]

Advances in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) research.

Author information

Department of Pharmacology and Toxicology, University of Arizona, College of Pharmacy, 1703 East Mabel Street, 85721, Tucson, AZ, United States. Electronic address:


Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is an autosomal dominant hereditary cancer syndrome with incomplete penetrance. It is caused by a germline amorphic allele of the FH gene, which encodes the TCA cycle enzyme, fumarate hydratase (FH). HLRCC patients are genetically predisposed to develop skin leiomyomas, uterine fibroids, and the aggressive kidney cancer of type 2 papillary morphology. Loss-of-heterozygocity at the FH locus that cause a complete loss of FH enzymatic function is always detected in these tumor tissues. Molecular pathway elucidation, genomic studies, and systematic genetics screens reported over the last two decades have identified several FH-inactivation driven pathways alterations, as well as rationally conceived treatment strategies that specifically target FH-/- tumor cells. These treatment strategies include ferroptosis induction, oxidative stress promotion, and metabolic alteration. As the fundamental biology of HLRCC continues to be uncovered, these treatment strategies continue to be refined and may one day lead to a strategy to prevent disease onset among HLRCC patients. With a more complete picture of HLRCC biology, the safe translation of experimental treatment strategies into clinical practice is achievable in the foreseeable future.


FH; Ferroptosis; Fumarate; HLRCC; Hereditary cancer syndrome; Hypoxia inducible factor; Iron homeostasis; KEAP1; Kidney cancer; NRF2; Papillary renal cell carcinoma; RCC; Succination

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center