Therapeutic Strategies for Hereditary Kidney Cancer

Abstract

The study of hereditary forms of kidney cancer has vastly increased our understanding of metabolic and genetic pathways involved in the development of both inherited and sporadic kidney cancers. The recognition that diverse molecular events drive different forms of kidney cancers has led to the preclinical and clinical development of specific pathway-directed strategies tailored to treat distinct subgroups of kidney cancer. Here, we describe the molecular mechanisms underlying the pathogenesis of several different types of hereditary renal cancers, review their clinical characteristics, and summarize the treatment strategies for the management of these cancers.

Intra-tumour molecular heterogeneity of clear cell renal cell carcinoma reveals the diversity of the response to targeted therapies using patient-derived xenograft models

“…The targeted drugs of tyrosine kinase inhibitors (TKIs) and anti-VEGF antibodies, such as Sorafenib, Sunitinib, Pazopanib and Axitinib are now recommended as the first- or second-line treatment for RCC. Sunitinib has been approved by the United States Food and Drug Administration (FDA) and European Medicines Agency as a first-line treatment for RCC [ 46 ]. The mammalian target of kanamycin (mTOR) inhibitor Temsirolimus has been approved for the first-line treatment of RCC patients with poor-prognosis, and Everolimus has been recommended for patients with advanced RCC or unresponsive to anti-VEGF therapies [ 42 ].…”

Identification of Novel Proteins Interacting with Vascular Endothelial Growth Inhibitor 174 in Renal Cell Carcinoma

“…At the time of RCC diagnosis, metastatic lesions are present in 20-30% of patients (20,21). Also, in 20-30% of patients with preoperative absence of metastases, after nephrectomies metastatic lesions appear or local recurrence of disease take places (22,23).…”

Hereditary Renal Tumor Syndromes: Update on Diagnosis and Management

“…Loss of FLCN causes an upregulation of mTOR activity which in turn, leads to cell growth especially after a 2 nd hit in the normal allele. 9 FLCN may play a role in the differentiation of renal tubular cells. 3 HIF is also stabilized by FLCN mutations, similar to what occurs in VHL, resulting in increased transcription of growth factor genes downstream of HIF.…”

“…53 Increased intracellular glucose levels, caused by shunting of glucose metabolism away from the Krebs cycle, produce NADPH-mediated reactive oxygen species which also further stabilize HIF. 9 This has the effect of creating a pseudohypoxic state similar to VHL which promotes cell growth. Of course, a second hit is required for an actual tumor to develop.…”