Abstract
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare autosomal dominant hereditary cancer syndrome characterized by a predisposition to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). It is known to be caused by germline mutations of the fumarate hydratase (FH) gene, which encodes an enzyme component of the citric acid cycle and catalyzes the conversion of fumarate to L-malate. Currently, there is no standardized treatment for HLRCC, which may be due in part to a lack of understanding of the underlying mechanisms. Here, the underlying molecular mechanisms by which the inactivation of FH causes HLRCC are discussed. Additionally, potential therapeutic pharmacological strategies are also summarized to provide new perspectives for the prevention and treatment of HLRCC.
Highlights
Hereditary leiomyomatosis and renal cell cancer (HLRCC), known as leiomyomatosis and renal cell cancer (LRCC), is a rare autosomal dominant disorder in which the affected individuals have a higher risk of developing cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC) [1]
A real-world outcome of the combination of bevacizumab plus erlotinib subjects in South Korea with HLRCC exhibited that the objective response rate (ORR) was 50% (5/10; 95% CI, 24 to 76) and the disease control rate was 90% (9/10; 95% CI, 60 to 98) [78]
The expression of PD-1/PD-L1 in 13 HLRCC is assessed for the first time using immunohistochemistry (IHC) and quantitative polymerase chain reaction, and the results have shown that PD-1/PD-L1 expression is limited to a small proportion of HLRCC patients, who are more likely to benefit from immunotherapy [105]
Summary
Hereditary leiomyomatosis and renal cell cancer (HLRCC), known as leiomyomatosis and renal cell cancer (LRCC), is a rare autosomal dominant disorder in which the affected individuals have a higher risk of developing cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC) [1]. Renal cell carcinoma in HLRCC was previously classified as type 2 papillary renal cell carcinoma. There is a tendency to develop into uterine and cutaneous leiomyomas as well as papillary RCC in individuals with HLRCC, and approximately 15% to 30% of HLRCC patients develop kidney cancer [4,5,6, 10, 11]. According to the latest analysis of 672 HLRCCs, 71.5% of patients had skin leiomyomas, 83% of women had uterine leiomyomas, and 34.9% of patients had RCCs [1]. Uterine leiomyomas appeared in 79% to 100% of women carrying the FH mutation [6, 11, 12]
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